The Claude D. Pepper
Older Americans
Independence Centers
2010
Annual Directory
and Report
FOREWORD
The 2010 Annual Directory and Report of the Claude D. Pepper Older Americans
Independence Centers is produced as a resource to provide information on the
research activities occurring at the Centers throughout the United States, as well
as a record of the publications and projects that have resulted from these
research activities.
The Pepper Centers are listed alphabetically with a synopsis of each of their major
research programs, supportive core units, training, publications, minority
research, and recognition and awards. All information contained in this directory
is based upon information supplied by each Center.
This document is searchable through Adobe Acrobat.
The 2010 Directory was prepared by the Claude D. Pepper Older Americans
Independence Center Coordinating Unit at Wake Forest University.
Claude Denson Pepper 1900-1989
Claude Denson Pepper was born near Dudleyville, Alabama on
September 8, 1900. He graduated from the University of Alabama
in 1921 and from Harvard Law School in 1924. After establishing a
general law practice in Perry, Florida, Pepper began his political
career with his election to the Florida House of Representatives in
1929. While working in the State Capitol in 1931 he met his future
wife, Mildred Webster outside the Governor's office in Tallahassee.
Claude and Mildred were married on December 29, 1936 in St.
Petersburg, Florida and for 43 years they were inseparable.
In 1936, Senior Florida Senator, Duncan Fletcher, died while in
office and Pepper was elected to the U.S. Senate to fill the vacant
seat. He quickly became a leader of the New Dealers in Congress
and a friend and confidant of President Franklin Roosevelt. Against
what seemed to be overwhelming opposition from conservative
isolationists in 1940 and 1941, he was able to lead the fight to pass
the Lend-Lease Act which allowed the U.S. to support the Allied
effort in World War II. In domestic affairs, he also made a name for himself as
somewhat of a "radical" by sponsoring bills for National Health Care, equal pay for
equal work for women, cancer and heart disease research programs, and a
minimum wage. Senator Pepper was co-author of legislation that established the
National Cancer Institute, the first of many National Institutes of Health.
Following his defeat for election to a third full term in the U.S. Senate in 1950,
Pepper returned to his law practice in offices in Tallahassee, Washington, and
Miami. In 1963, he returned to Congress as the Representative of the newlycreated 3rd Congressional District of Florida. Pepper was appointed as the
Ranking Democrat on the House Select Committee on Aging when it was created
in 1975 and became Chairman of that Committee in 1977. Serving as Chairman of
the Committee until 1983, he became known throughout the U.S. as "Spokesman
for the Elderly." In this capacity, he crusaded for an end to involuntary retirement,
strengthened the Social Security system, fought age discrimination, and pushed
for stronger legislation to end abuse of the elderly. He also chaired the U.S.
Bipartisan Commission on Comprehensive Health Care, a body created through
an amendment of his added to the 1988 Medicare Catastrophic Protection Act,
and he worked tirelessly to strengthen the Medicare program.
During Claude Pepper's five decades of public service, he was a strong and
effective advocate for millions of Americans in the areas of health care reform and
economic security. His numerous achievements will be felt by generations to
come: Americans guaranteed a decent wage, or saved from death or illness by
breakthroughs in biotechnology, or protected from age discrimination in the work
force or presented with a decent retirement income by the Social Security
program. He left monuments such as the National Institutes of Health, a
strengthened Medicare program, and a strengthened Social Security system. He
achieved his goal, "to lighten the burden upon those who suffer," many times
over. Senator Pepper died in Washington, D.C. on May 30, 1989.
2010 Pepper OAIC Director’s Contact Information
Boston University
Shalender Bhasin, MD
670 Albany St, 2nd floor
Boston, MA 02118
Email- [email protected]
Duke University
Harvey Jay Cohen, MD
Principal Investigator
Box 3003, DUMC
Durham, North Carolina, 27710
Email: [email protected]
Johns Hopkins University
Jeremy Walston, MD
Karen Bandeen-Roche, Ph.D.
Johns Hopkins Medical Institution
2024 E. Monument St., Suite 2-700
Baltimore, MD 21205
Email: [email protected]
Mount Sinai Medical Center
Albert L. Sui, MD
10th Floor, Annenberg Building
One Gustave L. Levy Place, Box 1070
New York, NY 10029
Email: [email protected]
University of California, Los Angeles
David B. Reuben, MD
David Geffen School of Medicine at UCLA
Multicampus Program in Geriatric
Medicine & Gerontology
10945 Le Conte Avenue, Suite 2339
Los Angeles, CA 90095-1687
E-Mail: [email protected]
University of Florida
Marco Pahor, MD
Professor and Chair
Department of Aging and Geriatric
Research, College of Medicine
Director Institute on Aging
University of Florida
1329 SW 16th Street, Room 5161
Gainesville, FL 32608
PO Box 100107, zip 32610-0107
E-Mail: [email protected]
University of Maryland, Baltimore
Andrew P. Goldberg, MD
VA Medical Center, GRECC (18)
10 North Greene Street
Baltimore, MD 21201
Email: [email protected]
University of Michigan
Jeffrey B. Halter, MD
University of Michigan
Geriatrics Center
CCGCB, Room 1111
1500 E. Medical Center Drive
Ann Arbor, Michigan 48109-0926
Email: [email protected]
University of Pittsburgh
Stephanie Studenski, MD
3471 Fifth Avenue; Suite 500
Pittsburgh, PA 15213
Email: [email protected]
University of Texas Medical Branch
Elena Volpi, MD, PhD
301 University Blvd. Rt. 8060
Galveston, TX 77555-0860
Email: [email protected]
Wake Forest University
Stephen Kritchevsky, PhD
Director, J. Paul Sticht Center on Aging
Wake Forest University School of Medicine,
Medical Center Boulevard
Winston-Salem, NC 27157-1051
E-mail: [email protected]
Yale University
Thomas M. Gill, MD, Director
Yale University School of Medicine
Adler Geriatric Center
20 York Street, DC-023
New Haven, Connecticut 06504
Email: [email protected]
BOSTON CLAUDE D. PEPPER OLDER AMERICANS INDEPENDENCE CENTER
FOR FUNCTION PROMOTING ANABOLIC THERAPIES
BOSTON MEDICAL CENTER • BOSTON UNIVERSITY • TUFTS UNIVERSITY • JOSLIN DIABETES CENTER
The Boston Claude D. Pepper Older Americans Independence Center
for Function Promoting Anabolic Therapies
2010 OAIC Annual Directory
Shalender Bhasin, MD, Director
P: (617) 414-2950 F: (617) 638-8217 E: [email protected]
Roger Fielding, PhD, Associate Director
P: (617) 556-3016 F: (617) 556-3083 E: [email protected]
Alan Jette, MPH, PhD, Associate Director
P: (617) 638-1985 F: (617) 638-1355 E: [email protected]
Rebecca A. Silliman, MD, PhD, Associate Director
P: (617) 638-8383 F: (617) 638-8387 E: [email protected]
Alicia Mackin, Administrator
P: (617) 414-2952 F: (617) 638-8217 E: [email protected]
Section I. Description of Center
The Boston Older Americans Independence Center (OAIC) is an interdisciplinary collaboration among
investigators from several Boston area academic research institutions. The Boston University and its affiliated
schools and hospital and Tufts University-affiliated institutions are most heavily represented in this
collaboration, although there are additional investigators from Harvard University/Joslin Diabetes Clinic and
New England Research Institute.
Mission
The Boston OAIC aims to bring experts from many different disciplines together to conduct research and to
train young scientists in the development of function promoting anabolic therapies (FPATs) for the prevention
and treatment of functional limitations and disability among older Americans.
Specific Aims
•
•
•
Develop an interdisciplinary research program that fosters the development of function promoting
anabolic therapies (pharmacological, nutritional, physical) for the treatment and prevention of agingassociated functional limitations;
Develop and interdisciplinary research career development program to enhance the training of a cohort
of investigators with expertise in function promoting anabolic therapies and aging-associated functional
limitations and disability;
Develop resource core facilities to support inter-disciplinary research programs;
Boston OAIC 2010 Annual Directory
•
Stimulate translation between basic and clinical research in function promoting anabolic therapies by
facilitating interdisciplinary collaborations.
Thematic Focus
The thematic focus of the Boston OAIC is the development of function promoting anabolic therapies. Thus,
research activities supported by Boston OAIC projects include, but are not limited to:
• Epidemiology of functional limitations and disability in older Americans;
• Mechanisms by which FPATs exert their anabolic effects and improve physical function;
• Identification of targets for discovery of FPATs;
• Discovery of biomarkers of efficacy of FPATs novel methods of outcomes assessment;
• Preclinical and clinical proof-of-concept efficacy studies of novel FPATs in appropriate model systems;
• Development of new and validated outcome measures for use in efficacy trials of FPATs
Section II: Research, Resources and Activities
The structure of the Boston OAIC consists of four cores that integrate 13 NIH-funded projects, linked by their
focus on physical functional limitations and FPATs in Older Americans:
• Leadership and Administrative Core (LAC)
• Research Career Development Core (RCDC)
• Three Research Cores (Physical Function Assessment Core, the Biostatistical Design and Analysis Core,
and the Small Animal Resource Core), and four Developmental Projects
• Pilot and Exploratory Studies Core (PESC)
LEADERSHIP AND
ADMINISTRATIVE
CORE (Leader: Bhasin)
RESEARCH CAREER
DEVELOPMENT CORE
(Leader: Silliman)
RESOURCE CORES AND
DEVELOPMENTAL
PROJECTS (Leader: Jette)
PILOT/EXPLORATORY
STUDIES CORE (PESC)
(Leader: Montano)
• Executive Committee
• Leadership Team
Currently Funded Projects:
• External Advisory Board
• Advisory Panel
• RC1. Physical Function
Assessment Core
(EAB)
• Mentoring Team
• PROMOTE Program
• Training Program
• LINK Program
• The FARM
• Evaluation Unit
RCD Current
Investigators:
• Dissemination and
Community Outreach
-
Chenchen Wang
-
Daniel White
RCDC Trainee Graduates:
-
Lisa Ceglia
-
Eric Bachman
-
Nancy Latham
-
Tuhina Neogi
• RC2. Biostatistical Design and
Analysis Core
• RC3. Small Animal Resource
Core
Developmental Projects (DP):
- DP1. IVR Administration of the
Late-Life FDI: Jette
- DP2. Continuous monitoring of
functional activities in home
setting: Wagenaar
- DP3. Application of a Systems
Biology Platform to Identify
Mode of Action of Function
Promoting Anabolic Therapies:
Collins
- DP4. Skeletal Muscle Precursors
(SMPs): Wagers
• PES1. Relationship between
Muscle Function and
Senescence Markers in
HIV+ Older Women:
Montano
• PES2. Mechanism-based drug
Discovery: Anabolic Effects
of a follistatin (BJS1), on
Skeletal Muscle Mass and
Physical Function in Older
Mice: Jasuja
• PES3. The role of testosterone
in the regeneration of young
and aged skeletal muscles
and synergy with the notch
and TGF- pathways: Serra
• PES4. Physical Function and
Metabolic Parameters in
Elderly Men Who Have
Opiod-Induced
Hypogonadism: Basaria
• PES5. Defective ankle joint
performance and myostatin
deficiency: Guo
Boston OAIC 2010 Annual Directory
• PES6. Dietary protein and
functional decline in the
Framingham Offspring
study: Moore
•PES7.Cognitive and functional
correlates of minimallyinvasive coronary artery
bypass: Jefferson
• PES8. Role of skeletal muscle
stem cells in age-related
muscle dysfunction: Hettmer
Boston OAIC Cores:
Leadership and Administrative Core (LAC)
Core Leader: Shalender Bhasin, MD
Telephone: (617) 414-2950
Fax: (617) 638-8217
E-Mail: [email protected]
The Leadership and Administrative Core (LAC) provides support for planning, evaluation, organizational, and
administrative activities relating to the other Cores and to the OAIC as a whole. A major mission of the LAC is
to provide integration and coherence across various OAIC activities.
The specific aims of the Leadership and Administrative Core are to:
• Oversee, guide and direct the Program through ongoing interactions with the External Advisory Board
(EAB), and NIA staff;
• Provide administrative support to the participating members including budget management, personnel
recruitment and management, procurement, and other logistical support, including review of salary
support for junior faculty supported through the Research Career Development Core (RCDC);
• Promote and maintain inter-disciplinary collaborations among OAIC investigators and cores within the
center, and with other OAICs, and investigators not currently in the OAIC through the PROMOTE
Program ;
• Oversee Pilot and Exploratory Studies Program, and recruit and support new inter-disciplinary pilot
projects, including review of Pilot/Exploratory Studies by a review panel;
• Evaluate overall program effectiveness through the EVALUATION Unit;
• Provide oversight of Resource Cores, review utilization of core resources by the OAIC users, assess
scientific opportunities for new utilization of core resources or development of new core facilities, and
reallocation of resources within or among cores;
• Facilitate commercialization of discoveries and innovations through the OAIC’s LINK program, in
conformity with the institutional and NIH regulations;
• Disseminate and share information about the OAIC among stakeholders, and maintain community
outreach and liaison through the Ambassador Program.
Claude D. Pepper Visiting Speakers. The LAC has coordinated an ongoing Seminar Series for the Boston
OAIC. This series is made up of monthly lectures presented by internationally recognized scientists in the field
of aging and functional limitation.
The Third Annual Research Retreat. The Boston OAIC organized two retreats, the first in October 2010 to
review ongoing research and foster new collaborations. The outcome of this retreat was the development of a
Boston OAIC 2010 Annual Directory
collaborative program project that will be submitted to NIH on May 25, and the development of collaborations
with the New England Primate Research Center for the use of primate models for investigation of age-related
functional limitations and function promoting therapies. The second retreat was held in conjunction with the
meeting of External Advisory Board in January 2011 and included presentations of research in progress. Drs
Stephanie Studenski, Thomas Gill, David Glass, and Andrew Goldberg were in attendance.
OAIC Website and Newsletter. We have established a web site and newsletter, both of which feature the
OAIC’s announcements, calendar of events, achievements, research, and publications. The website and
newsletters can be accessed at URL: www.bostonpeppercenter.org.
Research Career Development Core (RCDC)
Core Leader: Rebecca A. Silliman, MD, Ph.D.
Telephone: (617) 638-8383
Fax: (617) 638-8387
E-Mail: [email protected]
The purpose of the Boston OAIC Research Career Development Core (RCDC) is to recruit and train a cadre of
early career investigators who will be well-versed in principles of aging and geriatrics, and committed to careers
in aging research. They will be trained to conduct interdisciplinary translational research focused on improving
or enhancing functional independence in older adults. Moreover, they will develop the skills necessary to be
successful as academicians and in obtaining extramural research grant support.
For Boston OAIC trainees, the RCDC has as its goal to ensure that each trainee achieves a set of core
competencies. This goal has not changed. The core competencies will include:
•
•
•
•
•
•
•
In-depth knowledge of the processes of aging and geriatric syndromes.
In-depth knowledge of physical function as it relates to the disablement process;
Familiarity with the principles of interdisciplinary research and translational approaches to research in
aging across the continuum – from basic through clinical;
A practiced ability to write grants, abstracts and papers, and to present work orally;
Familiarity with ethical issues related to both human and nonhuman research;
In-depth knowledge of the theoretical aspects of translational and interdisciplinary research related to
their major areas of investigation; and
Advanced skills in research design, biostatistics, clinical trials design and implementation, physical
function assessment.
Current RCDC Trainees:
One trainee was funded in February 2009 (Dr. Wang) and one other was funded in June 2010 (Dr. White). One
additional RCDC trainee has been selected and will receive funding starting in June 2011, and one RCDC
trainee graduate is currently in a no-cost extension (Dr. Ceglia).
I.
Chenchen Wang, MD, Associate Professor of Medicine (Rheumatology), Tufts University School of
Medicine.
Dr. Wang is a board certified rheumatologist, who is working under the mentorship of Drs. Simin Meydani and
Timothy McAlindon at Tufts University to investigate the effects of Tai Chi on physical function, immune
modulation, and symptom relief in older individuals with osteoarthritis.
Dr. Wang has completed a collaborative, interdisciplinary procedure to validate and standardize the existing Tai
Chi mind-body research program for arthritis at Tufts Medical Center. Its specific aims are to provide a well-
Boston OAIC 2010 Annual Directory
validated and standardized Tai Chi program that will be used in large-scale studies to determine the comparative
effectiveness of this alternative therapy for arthritis. During the two year funding period, Dr. Wang and
colleagues brought together experts with considerable collective expertise in Tai Chi, exercise and OA. As
planned, they have developed a more detailed standard training Tai Chi protocol and validation. Patient focus
groups are being recruited and tested.
Dr. Wang’s research focuses on epidemiological and clinical studies of Complementary and Alternative
Medicine (CAM) and their interventions in chronic rheumatic conditions, especially osteoarthritis, rheumatoid
arthritis and fibromyalgia in older adults. During the current grant year, Dr. Wang attended the RCDC seminar
series and the Annual Pepper Center meeting. Dr. Wang received her first R01 this year and published the
results of one of her clinical trials in the New England Journal of Medicine. She has served as an ad hoc
member of the NIH Nursing Science: Adults and Older Adults Study Section and is an editorial board member
of the International Scholarly Research Network Rheumatology and Journal of Tang.
II.
Daniel K. White, PT, ScD, Research Assistant Professor (Physical Therapy), Boston University.
Dr. White is a physical therapist and Research Assistant Professor at the College of Health and Rehabilitation
Science: Sargent College at Boston University. His research interests are investigating the reasons for loss in
physical function and physical activity in older adults and people with knee osteoarthritis (OA). In addition to
doing research, Dr. White is pursuing a Masters in Science in Epidemiology at the School of Public Health at
Boston University. He is involved in teaching, particularly in research concepts at Sargent College, and is
working with Dr. Lisa Fredman to improve his scientific writing. Other mentors include Drs. Tuhina Neogi
(former RCDC trainee), David Felson, Alan Jette, and Rebecca A. Silliman. Dr. White is an active participant
in RCDC and Pepper Center seminars. He attended the Pepper Center Annual meeting for the first time this
year.
Dr. White’s primary research interest is in the disablement process of older adults with musculoskeletal
pathology. The focus of his research has been on risk factors of functional limitation and disability in older
adults with knee osteoarthritis. His clinical background in Physical Therapy along with formal training in
Rehabilitation Science and a post-doctoral fellowship in Rehabilitation Outcomes provide a strong foundation
for a career in clinical research. Dr. White has been working with mentor Dr. Lisa Fredman on “Positive affect
and habitual walking in older adults with knee OA: The MOST Study.” The specific aims have been finalized;
the introduction methods written; and preliminary analyses completed. Dr. White is investigating reasons why
the association of positive affect with habitual walking is null. Once this is clarified, a manuscript will be
completed and submitted for publication.
Dr. White’s RCDC aims to investigate the association of psychological factors with habitual walking in people
with knee OA. He is particularly interested in understanding the role positive affect or optimism has with how
much walking people with knee OA perform.
RCDC Trainee Graduates:
I.
Lisa Ceglia, MD, Assistant Professor of Medicine, Tufts University School of Medicine and Human
Nutrition Research Center on Aging at Tufts University.
Dr. Lisa Ceglia received her B.A. cum laude from Harvard University in 1993 and her M.D. from New York
University School of Medicine in 2001. She completed her Internal Medicine Residency at the New York
University Medical Center-Bellevue in New York, NY in 2004. She completed a 3-year, research track
Fellowship in Endocrinology at Tufts Medical Center, Boston, MA in June 2007.
Boston OAIC 2010 Annual Directory
As an RCDC trainee, Dr. Ceglia completed two Pilot studies: (a) A pilot study on the effect of vitamin D3
supplementation on skeletal muscle fiber size in older women and (b) A pilot study on the effects of potassium
bicarbonate and vitamin D insufficiency in skeletal muscle of aged rats.
Dr. Ceglia was appointed Scientist II at the Jean Mayer USDA Human Nutrition Research Center on Aging at
Tufts University in April 2010. She is in her second year of a KL2 Career Development Award within the Tufts
Clinical and Translational Science which began in July 2009. She will complete a Master’s in Clinical and
Translational Science at the Tufts Sackler School of Graduate Biomedical Sciences in May 2011. She will
submit a manuscript focused on her human pilot study by June 2011 and another based on her rat pilot study by
September 2011. An NIH grant application submission will follow in October 2011.
II.
Nancy Latham, PhD, PT, Research Assistant Professor at the Health and Disability Research Institute
at Boston University.
Dr. Nancy Latham, PhD, PT is a Research Assistant Professor at the Health and Disability Research Institute in
the Boston University School of Public Health. Her teaching, research and publications reflect her interest in
applying methods from the field of clinical epidemiology, such as observational cohort studies, randomized
clinical trials, systematic reviews and meta-analyses, to geriatric rehabilitation. In 2007 she was awarded a
Mary E. Switzer Distinguished Fellowship from the National Institute of Disability and Rehabilitation Research
which explored participation outcomes following rehabilitation.
As an RCDC trainee, Dr. Latham made progress on her goal of expanding her understanding of how tele-health
technology can be used to extend the benefits of rehabilitation after standard therapy ends. In her work on the
Pepper development project, Dr. Latham met with many members of the team from the MISU and received
training from them that has improved her understanding of the process of developing tele-health interventions.
Dr. Latham has also expanded her skills in setting up clinical research projects in older adults and designing
electronic data collection systems, as she is an investigator on a randomized controlled clinical trial of exercise
training in older people after hip fracture and on a longitudinal cohort study of older adults with mobility
disability.
As an RCDC trainee, Dr. Latham has focused on two projects. First, she completed the systematic review of
strength training to improve function in older adults. It was published in the Cochrane website in the fall of
2009. This work created a very large database of 121 trials which enrolled 6700 participants. A secondary
publication exploring the effects of strength training on older adults with osteoarthritis is in press; two
additional manuscripts are in preparation.
The second project is the development of an interactive voice recognition version (IVR) of a functional measure
for older adults, the Late Life Function and Disability Instrument Computer Adaptive Test (LLFDI-CAT). This
is a Pepper Center Developmental Project.
III.
Tuhina Neogi, MD, PhD, Associate Professor of Medicine (Rheumatology), Boston University School
of Medicine.
Dr. Neogi is a rheumatologist and conducts clinical epidemiologic research. Dr. Neogi’s research interests
include the epidemiology and management of osteoarthritis, the role of bone in the pathogenesis of
osteoarthritis, mechanisms of osteoarthritis-related pain, risk factors and management of gout, consequences of
gout and hyperuricemia, outcome measures in rheumatoid arthritis and vasculitis, and management of vasculitis.
Boston OAIC 2010 Annual Directory
In addition to research, Dr. Neogi is also involved in teaching, particularly of epidemiologic concepts through
evidence-based medicine journal clubs and development of new curricula. She also has a clinical practice
focused on vasculitis.
As an RCDC trainee, Dr. Neogi attended NIH Pain Symposia and had Dr. Lars Arendt-Nielsen as a visiting
professor to expand her knowledge regarding pain research. She created a new protocol for somatosensory pain
evaluations, which has now been administered to over 1000 participants of an ongoing cohort study. She is in
the midst of analyzing these data in preparation for abstract submissions to two international meetings.
RCDC Farm
The FARM program at the Boston OAIC identifies potential candidates for RCD trainee awards from diverse
disciplines of internal medicine early in their careers and nurture and guide them towards interdisciplinary
careers in aging research. These candidates are typically second or third year residents or first year subspecialty
fellows in Endocrinology and Geriatric Medicine. FARM candidates take part in Boston OAIC research
meetings and biannual retreats and conduct interdisciplinary research that is broadly related to the Boston OAIC
theme of functional limitations in older Americans and function promoting anabolic therapies.
We have identified several post-doctoral fellows who are likely to transition to faculty positions within the next
several years. These include Donato Rivas, PhD, supported by a Diversity Supplement, working with Dr.
Fielding; Dr. Jessica Eng, a first year Geriatric Medicine Fellow who has been granted funding by the John A.
Hartford Foundation to work with Dr. Silliman; Dr. Christine Liu, a third year Geriatric Medicine Fellow
working with Dr. Fielding who will be joining the faculty in the Department of Medicine, Section of Geriatrics
in July, and Dr. Devyani Misra, a third year Rheumatology Fellow (also trained in Geriatric Medicine) who is
working with Dr. Neogi, a former RCDC trainee. These trainees participate in our RCDC seminars, benefiting
both from learning substantive content and also learning grantsmanship skills. We anticipate that they will be
competitive candidates for RCDC funding in the future.
Resource Core I (RC1): Physical Function Assessment Core (FAC)
Core Leader: Roger Fielding, PhD
Phone: (617) 556-3016
Fax: (617) 556-3083
E-Mail: [email protected]
Core Leader: Alan Jette, PhD
Phone: (617) 638-1985
Fax: (617) 358-1355
E-Mail: [email protected]
Core Leader: Thomas Storer, PhD
Phone: (617) 414-2942
Fax: (617) 638-8217
E-Mail: [email protected]
The Physical Function Assessment Core (FAC) seeks to provide the necessary infrastructure to perform
standardized, valid and reliable measures physical impairments, function, and disability across the array of
clinical studies supported or associated with the Boston OAIC. In addition, this same core will provide support
for the assessment of physical impairments and function across an array of basic (animal model) studies
associated and supported by or affiliated with the Boston OAIC. The leadership of this core has collaborated
extensively over the past ten years, has extensive experience in the application of these measurements across a
Boston OAIC 2010 Annual Directory
wide range of cross-sectional and intervention studies in older adults, and is uniquely cross-trained in the
assessment of muscle impairments and functioning in animal models. This uniquely structured interdisciplinary
core will provide a forum for performing these validated standardized assessments and to further refine and
expand the availability of new techniques to assess physical functioning and functional capacity across a range
of species from rodents to humans.
The specific aims of the FAC are to:
1. Provide a focal point for interdisciplinary collaboration by Center investigators in the development,
evaluation, and application of new and existing tools and instruments to assess muscle impairments,
functional limitations, and disability in older adults and function promoting therapies.
2. Promote and foster the development and refinement of tools and instruments to assess muscle
performance and physical functioning in animal models of aging.
3. Standardize equipment and operating protocols for the assessment of muscle performance & functional
limitations in human and animal studies. Implement and maintain personnel training and certification for
the application of standardized muscle performance and functional limitations testing protocols.
Establish and maintain equipment calibration for use across all Center studies.
The FAC has been established and is being administered under the direction of the core leaders, Drs. Fielding,
Jette, and Storer. Components of the FAC are housed at both Boston University and Tufts University and the
FAC is truly an inter-institutional collaboration. The FAC leadership meets regularly to discuss core activities
and to review requests for utilization of FAC services. The FAC leadership has announced the services of this
core through several different mechanisms including the Boston OAIC website, announcements at OAIC
seminars and meetings, and interactions with professional colleagues at our respective institutions. Continued
outreach to OAIC-affiliated investigators and non-OAIC investigators will be made in year 4 by the FAC staff.
Core Utilization: Requests for the proposed utilization of FAC services are reviewed at regular meetings.
Access to FAC services are based on the following criteria: relevance to the theme and focus of the OAIC;
scientific merit; and availability of resources with the FAC. In addition, priority will be given to support of
junior investigators embarking on research that is directly relevant to the theme and focus of the OAIC.
The FAC is providing direct support to the pilot and developmental projects supported by the Boston OAIC and
to other independently funded studies that are scientifically relevant to the mission of the Center (see core
utilization table). Three mechanisms have been established to provide FAC support for studies. OAIC pilot
and developmental projects can utilize FAC staff to assist with and conduct proposed assessments for approved
protocols. In addition, OAIC-related studies at the respective participating institutions can utilize the services
of the FAC on a fee for service basis to perform the available measurements. Finally, direct consultative
services regarding the appropriate design and utilization of measures in future studies that are relevant to the
OAIC mission are also currently available.
For human studies, the FAC combines the resources of the Laboratory of Exercise Physiology and Physical
Performance (LEPPP) at Boston University School of Medicine (directed by Dr. Storer), and the Nutrition,
Exercise Physiology, and Sarcopenia Laboratory at Tufts University (directed by Dr. Fielding). These two
laboratories employ state of the art equipment and standardized, reliable and valid protocols for assessing
muscle performance and physical function in human studies. The laboratories are conveniently located with
respect to their parent institutions’ clinical research units. The laboratories are equipped with Keiser pneumatic
resistance machines that are integrated with a sophisticated electronics package with computer interface that
allow precise measurement and recording of muscle strength, power, fatigability, contraction velocity, and
other muscle performance characteristics. Both institutes also possess the ability to capture functional
Boston OAIC 2010 Annual Directory
(aerobic) capacity and other measures of cardiopulmonary fitness such as peak work rate, anaerobic threshold,
and work efficiency are measured with a metabolic measurement system with capabilities of measuring
metabolic rates from rest to maximal exercise. The systems are integrated with complete 12-lead EKG,
electrically braked cycle ergometers, and motor driven treadmills. In addition, the laboratory has been equipped
to measure physical function in tasks such as stair climbing, gait speed, load carries, lift and reach tasks,
and reaction/movement times. Both laboratories have established track records of successfully using these
resources in clinical trials of function promoting therapies. The necessity of having assessment facilities at both
institutions is that these services can be provided to projects being conducted at both institutions. Core usage is
nearly equally split between institutions. In addition, a major hurdle in conducting clinical trials in older adults
is getting these individuals to leave their homes and come to the medical center for evaluation. Our approach
will allow for a broader coverage of several geographic regions in the greater Boston area thus increasing our
outreach into communities of older adults for clinical studies. The expertise associated with the assessment of
self-reported disability and other self-report measures is located in Dr. Jette’s institute and these instruments can
be easily be managed and administered across both institutions
The FAC also provides self-report instruments to measure functional limitations and disability using
protocols developed and tested by Dr. Jette and colleagues in the BU Health & Disability Research Institute.
Quality Control. Obtaining reliable and valid muscle and functional data in all Center studies is critical to each
project’s ultimate success. All FAC labs have established standardized procedures for training and certification
of all staff involved in outcome measurement and maintains strict quality control procedures that are standard
across all OAIC labs. Quality control procedures include:
• Outcome Measurement Manuals for all muscle and function measurement protocols,
• Observation of data collection staff in the operation of each protocol at the end of training and as part of
the certification and re-certification procedures;
• Periodic calibration of instruments will assure accuracy and precision.
• Completion of staff field logs to record measurement issues as they arise and as a place to record
solutions to be implemented across all participating labs;
• FAC Certification: Clinical research coordinators can now undergo a training and certification program
for each of the physical performance assessments that are performed by the FAC. This training and
certification include interactive practice sessions and a formal skills evaluation for certification.
Regular FAC meetings are currently held with laboratory staff to discuss progress, problems encountered,
solutions reached and as an interdisciplinary forum to develop protocols to be included in new research
applications. Recent specific topics have been the review of the SPPB protocol, assessment of muscle strength
and power in older adults, and the proper measurement of gait speed.
Innovation. The FAC provides a comprehensive assessment of muscle performance and physical functioning
for both animal and human studies. It is also emerging as a critical interdisciplinary resource for collaboration
on the development of new research applications by Center investigators.
FAC Core Utilization: A total of 7 OAIC projects are utilizing the FAC. In addition, 19 external projects are
receiving services from the FAC.
Pepper Center studies supported by the OAIC
PI
Basaria, Shehzad
Ceglia, Lisa
Title
Physical function and cardiovascular risk factors
in elderly men taking opioid analgesics for
Chronic Non-Cancer Pain
A pilot study of the impact of vitamin D on
Institution
Funding Source
Boston
University
OAIC Pilot &
Exploratory Study
Tufts HNRCA
OAIC Pilot &
Boston OAIC 2010 Annual Directory
Jette, Alan
Montano, Monty
Rivas, Donato & Fielding,
Roger
Wagenaar, Robert
Wang, Chenchen
muscle performance in elderly women
Interactive voice recognition (IVR) administration
of LL-FDI CAT
Relationship between Immunosenescence and
Muscle Function in HIV+ Women
Mechanism of skeletal muscle anabolism in
response to progressive resistance exercise in
older men and women
Continuous monitoring of functional activities in
home and community based setting
Tai Chi and Knee Osteoarthritis
Boston
University
Boston
University
Tufts HNRCA
Boston
University
Tufts Medical
Center
Exploratory Study
OAIC Developmental
Project
BU CTSI/OAIC Pilot
OAIC Pilot &
Exploratory Study
OAIC Developmental
Project
NIH/NCCAM
External studies supported by the OAIC
PI
Araujo/McKinlay
Bhasin
Bhasin/Basaria
Title
The Boston Area Community Health/Bone Survey
Effects of testosterone replacement on muscle
performance and physical function in older men
(TOM)
Follow-up of participants in a randomized,
placebo-controlled testosterone trial of older men
with mobility limitation (TOM 2)
Testosterone Replacement and Atherosclerosis
Progression in Older Men with Low Testosterone
Levels(TEAAM)
Testosterone dose response in surgically
menopausal women (TDSM)
Optimal protein intake and anabolic response in
older Americans
The SARM Trial
Bhasin
The Testosterone Trials
BUMC
Bhasin
The role of 5 alpha reductase in mediating
testosterone actions
BUMC
Fielding
Lifestyle Interventions and Independence for
Elders (LIFE) Study
Tufts
HNRCA
NIH/NIA
Fielding
Lower Extremity Power and Function in the
Elderly (Study 1 Follow-Up)
Tufts
HNRCA
NIA
Fielding
Lower Extremity Power and Function in the
Elderly (Power Training Intervention - Study 2)
Tufts
HNRCA
NIA
Fielding
Whey Protein Supplementation and Resistance
Exercise Study
Effects of Potassium Bicarbonate Intake on
Skeletal Muscle Catabolism During Short Term
Energy
VIVE (Vitality, Independence, and Vigor in
Elders) Effects of an Exercise and Nutrition
Program on functionality in the elderly
Efficacy of Nutritional supplementation on
physical-activity mediated changes in physical
functioning in older adults at risk for mobility
Tufts
HNRCA
Tufts
HNRCA
Dairy Management
Inc
Unilever
Tufts
HNRCA
Nestec Inc
Tufts
HNRCA
Nestec Inc
Bhasin
Bhasin/Solvay
Pharmaceutical
Bhasin
Bhasin/Moore/Apovian
Fielding
Nelson
Fielding
Institution
NERI
BUMC
Funding Source
NIA
NIA
BUMC
NIH-NIA
BUMC
Solvay
Pharmaceutical
BUMC
NIH/NICHD
BUMC
NIH
BUMC
Ligand
Pharmaceuticals, Inc
University of
Pennsylvania
NIH
Boston OAIC 2010 Annual Directory
Roberts
Dawson-Hughes
Weiner, Daniel
disability (The VIVE 2 study)
Comprehensive Assessment of Long-Term Effects
of Reducing Intake of Energy (CALERIE)
Vitamin D and Muscle Strength
Effects of exercise training on cognition and
functional performance in CKD
Tufts
HNRCA
Tufts
HNRCA
NIA
Tufts
Medical
Center
NIH/NIDDK
USDA
A wide array of basic studies and clinical trials are presently benefitting from the collective resources of this
core. Increasingly, due to pressure from regulatory agencies and a defined need to assess more distal outcomes
in trials of function promoting therapies in older adults, treatments of muscle loss (sarcopenia) have been
directed to assess therapeutic efficacy by assessing subjective symptomatology (eg: fatigue, energy, difficulty in
activities of daily living) and objective measures of physical functioning (eg: gait velocity, chair stand capacity,
stair climbing performance). In addition, novel therapeutic interventions targeted at specific pathophysiological
changes and impairments in older individuals with functional limitations must continue to be examined. Finally
the emergence of the ability to genetically modify laboratory rodents has increased the need to adequately
assess the phenotype of these animals with respect to physical impairments such as voluntary muscle strength
and functional limitations such as gait, maize performance and balance. The key personnel affiliated with the
FAC are uniquely qualified to provide the necessary support and infrastructure for this core.
The major plans for Year 4 will be to continue to consolidate and standardize the assessment procedures at both
satellite locations (Tufts and BU) of the FAC. In addition, the FAC leadership will begin to meet with
investigators whose research may directly benefit from the resources available through the FAC. We plan on
continuing to expand the number of investigators that use these resources in Year 4.
Resource Core II (RC2): Biostatistical Design and Analysis Core (BDAC)
Core Leader: Thomas G. Travison, PhD
Phone: 617-414-2971
Fax: 617-638-8217
E-Mail: [email protected]
The Biostatistical Design and Analysis core (BDAC), implemented in January 2011, seeks to provide
collaborative support in the design, execution and analysis of clinical trials and epidemiology studies conducted
at the Boston OAIC. In addition the core seeks to foster internal and external collaborations in the epidemiology
of aging-related disability, and to provide mentoring and collaborative opportunities for students and junior
faculty in quantitative aspects of the study of physical function and impairments in aging. The core’s Specific
Aims are:
1. To provide methodologic and quantitative expertise in the planning and execution of Boston OAIC
projects.
2. To provide data analytic support for projects conducted in the Boston OAIC.
3. To promote the training and development of quantitative scientists with expertise in the design and
analysis of basic science studies, clinical trials and epidemiologic investigations in physical strength and
function in aging populations
.
A large number of basic studies and clinical trials will benefit from the existence of this new resource core. The
evolution of clinical trials and studies in complex syndromes of aging necessitates that quantitative scientists
Boston OAIC 2010 Annual Directory
have broad-based knowledge in statistical methods and familiarity with the specific challenges of studies in agerelated disease. Centralized expertise and support in the design and analysis of ongoing and future OAIC
projects will insure that they are properly powered and evaluated using valid and appropriate methodology. In
addition to the existence of the core will increase the rapidity with which findings can be disseminated within
the scientific community and to the public.
The BDAC provides direct support to pilot and developmental projects associated with the Boston OAIC and to
other independently funded studies that are scientifically relevant to the mission of the OAIC. These include:
design activities (e.g. simulation and power calculation, critical review of protocols and data collection
materials); activities in support of project execution midstream (e.g. enrollment assessment, interim analyses),
and activities supporting study completion (e.g. end-study data analyses, abstract and manuscript production).
Costs for services for non-OAIC affiliated projects are supported by a charge back scheme as well as direct
salary support (FTE) for core members.
Current utilization of core resources: The BDAC has quickly become an integral and important part of the
further development of research directed toward the OAIC goals. Projects currently supported (either in design
or analytic services) by core resources and/or staff include but are not limited to:
•
Inflammatory biomarkers, physical activity and the development and progression of frailty in older men
and women (PI: E Benjamin)
•
Association of female androgens and cardiometabolic illness (PIs: A Coviello, J Murabito)
•
GH/IGF-1 as mediators of anabolic action (PI: C. Serra)
•
Testosterone administration and iron metabolism (PI: E. Bachman)
•
Myostatin antagonism in healthy aging (Pi. W Guo)
•
Telerehabilitation following spinal cord injury (PI: A. Jette)
•
Multi-modaility interventions for complex illnesses in aging (PI: Bhasin)
•
Intensity and dispersion of physical activity in relation to OA (PI: White)
•
Nutritional/hormonal interventions for maintenance of physical function in aging men (PI: Bhasin)
•
Causal modeling of contributions of sex hormone-binding globulin to physical dysfunction and
prediabetic illness (PI: Travison)
Core members are also involved in local, national and international collaborations (externally supported) in the
areas of metabolism and aging.
Work supported by the core has been or will shortly be presented at national and international meetings such as
those of the Endocrine Society, American Heart Association, European Congress on Endocrinology, and others.
Resource Core III (RC3): Small Animal Resource Core (SARC)
Core Leader : Ravi Jasuja, PhD
Phone : 617-638-8299
Fax : 617-638-8217
E-Mail : [email protected]
An essential component of the preclinical proof-of-concept studies of function promoting therapies is the
assessment of their effects on body composition, muscle performance and physical function. Also, the ability to
genetically modify laboratory rodents has increased the need to reproducibly and quantifiably assess the
phenotype of these animals with respect to body composition and physical function. The Small Animal
Boston OAIC 2010 Annual Directory
Resource Core (SARC), implemented in January 2011, provides the necessary support and infrastructure for
these services by accomplishing the following specific aims:
1. Provide a focal point for interdisciplinary collaboration by Boston OAIC investigators in the application
of existing and new tools and instruments to assess muscle impairments, metabolic alterations and
quantification of physical function response to the function promoting therapies.
2. Provide standardized, state-of-the-art methods and instruments to assess body composition (lean body
mass, whole body and regional fat mass, skeletal muscle mass) in animal models of aging and in response to
function promoting therapies.
3. Provide standardized equipment and operating protocols for the assessment of muscle performance and
physical function in preclinical models of aging.
4. Provide enriched populations of muscle progenitor cells from animal models
5. Implement and maintain personnel training and certification for the application of standardized muscle
performance and physical function testing protocols, and maintain equipment calibration for use across all
projects.
Services available through the core:
1. Longitudinal Assessment of Body Composition by NMR and MicroCT Scanner. Body composition of
mice and rats will be determined by small animal NMR (EchoMRI 900; echoMRI, TX) and LaTheta™ CT
scanner calibrated and certified for non-invasive monitoring of small experimental animals.
Employing a high-performance X-ray generator, the CT scanner provides high resolution multi-images in a
short time. Quantitative data, such as fat weight, bone density, bone mineral content and morphological data
(including volume, area) is also provided, utilizing X-ray attenuation calculations related to specific tissue
structures. The CT scanner provides a scout image as a preliminary image, transverse images, and threedimensional images reproduced from scan data. The instrument possesses fast scanning capability (4.5 sec per
one slice image) at High resolution (60 μm Min.) with low radiation dose to animal.
2. Measures of Muscle Performance and Physical Function
a. Grip strength. Grip strength serves as a global measure of muscle strength, and will be assessed by a
computer-integrated grip meter (Columbus Instruments) using standardized laboratory protocols. Animals grasp
a bar linked to a computer-integrated force transducer with their front limbs and are then drawn away from the
bar. Peak force is recorded as the outcome measure.
b. Ex-vivo Muscle Mechanics. Muscle mechanics measurements are performed on an Intact Muscle Test
System (1205A 10N force, Aurora Scientific, Inc., Ontario, Canada)). The EDL and SOL muscles will be
dissected from hindlimbs while the animal are under a deep plane of anesthesia. Muscles will be immersed in a
vertical bath, circulated with 25°C oxygenated Ringer solution, buffered to pH 7.4. The distal tendon will be
tied to a nonmovable post and the proximal tendon attached to a servomotor. Muscle length will be adjusted to
the optimal length (Lo) at which maximal twitch force is reached. SOL and EDL maximal tetanic forces will be
determined using 80 HZ-1500 ms and 120 HZ-500 ms supramaximal electrical pulses, respectively following
the standardized protocols. The quantifiable outcomes will include contraction and half-relaxation times, forcevelocity relationships and the maximum velocity of unloaded shortening extrapolated from the force-velocity
curves
c. Aerobic capacity. The Oxymax System is linked to an enclosed treadmill for monitoring metabolic
performance under exercise. The laboratory also houses a multi-lane motorized treadmill (Columbus
Boston OAIC 2010 Annual Directory
Instruments) for determining exercise capacity (running speed, time, distance, work and power) and conducting
exercise training studies.
d. Physical Activity. The metabolic chambers are equipped with photocells that are aligned to the X-, Y- and
Z-axes to quantify habitual physical activity in the horizontal (ambulation) and vertical (rearing) planes.
3. Metabolic Outcomes Assessment
3a. Energy Expenditure and Basal Metabolic Rate. Energy expenditure and basal metabolic rate in mice and
rats will be determined using a computer-integrated Oxymax Open Circuit Calorimeter System (Columbus
Instruments) linked to collection chambers to quantify VO2, VCO2, respiratory exchange ratio, and basal
metabolic rate. The system is housed within our laboratory in a specially-designed temperature controlled room
with 12 hour light and dark cycles. To capture metabolic parameters under fed and fasted conditions, mice will
first be placed in individual collection chambers supplemented with food, bedding and water for 24 hrs. The
experimental chambers closely resemble standard housing conditions with the exception that room air is
monitored and delivered at a specified rate and then air is sampled and quantified from the cage at a specified
frequency and rate. At 24 hrs, food will be removed from the chambers and animals will be examined under
fasting conditions for an additional 24 hrs. This time course enables the measurement of experimental animals
during light and dark hours under both fed and fasted conditions.
The oxygen and carbon dioxide analyzers are calibrated prior to every experiment using a standardized
laboratory protocol. The system accommodates 8 mice or 4 rats per experiment.
3b. Core Body Temperature. Core body temperatures of mice and rats will be measured by using an infrared
high performance non-contact Raynger MX4 thermometer (Raytek Portable Products). In longitudinal
experiments, core body temperature can also be measured by using implantable microchips containing
temperature transponders (IPTT-100) and a hand-held reader (Bio-Medic Data Systems, Delaware).
3c. Energy Intake. The use of specialized feeding cages allows for the quantification of daily food intake over
several days. This is a key outcome measure and aids in the design of pair feeding experiments.
3d. Insulin Sensitivity and Glucose Tolerance. The SAPC laboratory has the ability to perform glucose
tolerance test, insulin tolerance test, and hyperinsulinemic clamp studies in mice.
Core Utilization. The SARC is providing direct support to the pilot and developmental projects supported by
the Boston OAIC and other independently funded studies that are scientifically relevant to the mission of the
Center. A list of projects that are utilizing the SARC is shown below:
PI
Title
Neil B Ruderman Sirt1 and endothelial function
Services Provided
Metabolic and physical function
Shalender Bhasin Mechanisms of Androgen Action
NMR imaging, Physical Function,
μCT scanning and exercise capacity
E. S. Bachman
Hepcidin and physical function
Carlo Serra
IGF signaling in Muscle
anabolism
NMR imaging, Metabolic assessments
and exercise capacity
NMR imaging, Physical Function,
μCT scanning and exercise capacity
Wen Guo
Mechanisms of myostatin action
Ken Walsh
AKT/mTOR in skeletal hypertropy Exercise capacity, NMR and Habitual
activity monitoring
David A Seldin
Molecular mechanisms of
Ameloidopathy
NMR imaging, Physical Function,
μCT scanning and exercise capacity
Neuromuscular coordination,
Spontaneous activity, NMR imaging
Boston OAIC 2010 Annual Directory
All projects that are utilizing SARC services received IACUC approval before they initiated the use of core
resources. Evidence of continuing IACUC review and approval is documented and the approved version of the
IACUC protocol is kept in the core office.
Animals are housed at AAALAC accredited facilities of BUMC. Routine veterinary care to animals is provided
daily by veterinary technicians under the direction of one of the attending veterinarians. Animal use is
additionally monitored by the Coordinator for Training and Compliance. The veterinary staff at each of the
participating institutions has substantial experience in maintaining older mice.
During the coming year, the Core will streamline its services, implement an electronic application process, and
add more advanced methods for the assessment of aerobic performance during exercise.
Developmental Projects:
Developmental Project I: Computer-Adapted Testing (CAT) instrument for the Late-Life Function and
Disability Instrument (LATE-LIFE FDI-CAT)
Project Investigators: Alan Jette, Ph.D., Nancy Latham, Ph.D., Health & Disability Research Institute,
BU School of Public Health; Robert Friedman, MD, Director, BUMC Medical Informatics Unit
Although an Institute of Medicine Expert Panel emphasized the pressing need for efficacy trials of Function
Promoting Therapies in patients with measurable functional limitations outcomes, the length and complexity of
the physical function measures has raised concerns over respondent burden, administration time, and data
collection costs. There exists an urgent need for the development and testing of innovative methodologies for
the measurement of physical function for future efficacy trials in humans.
Contemporary methods of item modeling and scaling coupled with new data collection models such as
computer adaptive testing (CAT) provide an innovative method for assessing patient-reported outcomes and
have the potential to simultaneously achieve measurement breadth, precision, and feasibility across the broad
range of functional abilities of older adults. CAT is a computer algorithm that matches items to respondents.
The CAT version of the Late-Life FDI achieves some efficiency in administering patient-reported outcome
instruments and represents an innovative approach to improving outcome assessment for use with older persons.
This proposal builds upon the advantages of a CAT instrument to develop more efficient and sensitive
functional outcome data collection that can be used in clinical research.
Development Project 1 will develop an Interactive Voice Response (IVR) system to administer the
Late-Life FDI CAT for assessment of self-reported physical function.
The principal aims of this project are to:
♦ Develop an IVR system to administer the Late-Life FDI;
♦ Pilot test IVR technology for administering the Late Life-FDI CAT by telephone by comparing it with
live telephone interviews of the same instrument in older adults.
♦ Compare the test retest reliability of IVR vs. interviewer administration of the Late-Life FDI CAT.
Our primary hypothesis is that IVR administration, in comparison to live administration of the LL-FDI CAT
instrument, will yield comparable scores and reliability at considerable time savings for researchers.
Developmental Project II: Continuous monitoring of functional activities in the home and community
based setting
Principal Investigators: Robert C. Wagenaar1 and Thomas D.C. Little2.
1
Department of Physical Therapy and Athletic Training, Sargent College of Health and Rehabilitation Sciences,
and
2
Department of Electrical and Computer Engineering, College of Engineering, Boston University.
Boston OAIC 2010 Annual Directory
Functional decline with aging increases the risk of disability, dependency, falls, and mortality; therefore, there
is growing interest in the development of function promoting anabolic therapies (FPTAs) for the treatment and
prevention of aging-associated functional limitations. In addition, very limited information is available on how
FPATs affect the levels of functional activities (e.g., walking, stair climbing, running, biking, etc.) in the home
and community based setting. It has been argued that functional activities in the home environment are an
excellent integrated measure of physical function. It is open to further investigation whether administration of
FPATs results in clinical benefits measurable at the level of functional activities. In other words, there is a
pertinent need for the development of reliable, valid and responsive measures for the assessment of (reduced)
level of activity in the evaluation of older individuals participating in clinical trials of FPATs. In general, a
thorough understanding of functional limitations in older Americans requires the continuous measurement of
functional activities as well as environmental constraints in the home and community based setting. To that end,
there is a growing need for the development and implementation of new and innovative functional activity
monitor (FAM) schemes, including algorithms derived from biomechanics/coordination dynamics and
sensoryspatial detection for functional activities in the home and community based setting, that will enhance our
ability to measure functional limitations that are responsive to FPAT administration.
Previous work by our research group has demonstrated that functional activities in the home and community
based setting lasting longer than 5 seconds can be accurately and reliably assessed with an Activity Monitor
(AM). The advantage of the AM compared to questionnaires is that it allows for continuous assessment of
functional activities, which will improve the responsiveness to treatment effects. However, its current design
has a number of limitations related to maximal hours of date recording, energy supply, the extraction of
recorded date, the size of the data-logger attached to the body, the algorithms used in data-reduction and the
assessment of environmental barriers. Results from current work done by our research team regarding a newly
developed small wireless functional activity monitor (FAM) showed no significant differences and a high
correlation coefficients between the Optotrak system (the golden standard in 3 dimensional motion detection
and analysis system) and the FAM that includes one gyroscope and accelerometer in evaluating the kinematics
of different postural strategies during lifting objects.
Based on this progress in the development of the present technology, the specific aim within this project is to
evaluate the test-retest reliability, validity and responsiveness of a small sized wireless functional activity
monitor that can continuously record functional activities in the home and community based setting of a
population with limited physical functional daily activities.
Developmental Project III: Application of a Systems Biology Platform to Identify Mode of Action of
Function Promoting Anabolic Therapies
Principal Investigator: James Collins, Ph.D.
Based on the recommendation of the External Advisory Board, the Systems Biology Core was converted into a
development project. In this project we plan to take a top-down approach, and develop and apply integrated
experimental-computational techniques to reverse engineer and analyze naturally occurring mammalian gene
regulatory networks involved in age-related functional limitations and in mediating the actions of function
promoting anabolic therapies. The specific aims of this unique developmental project are:
Specific Aim #1: To apply a systems biology technology platform which uses reverse-engineered gene
networks combined with expression profiles to identify the mode of action of testosterone
Specific Aim #2: To provide a systems biology technology platform which uses reverse-engineered gene
networks combined with expression profiles to identify key genetic mediators and mediating pathways that
mediate the effects of testosterone on the prostate and the skeletal muscle
Boston OAIC 2010 Annual Directory
Specific Aim #3: To provide a systems biology technology platform which uses expression profiles to identify
and reconstruct regulatory networks underlying aging processes
Studies and Results: Androgen supplementation to young and older men increases muscle mass and reduces
fat mass. Although these anabolic effects of androgen are well supported in-vitro and in-vivo, prostatic side
effects have limited enthusiasm about their clinical use for metabolic interventions. Mechanisms of androgen
action have been under intense investigation for the past several decades. Both industry and academia have been
developing novel structural testosterone analogs to identify Selective Androgen Receptor Modulators (SARMs)
which would retain promyogenic, anti-adipogenic effects of androgens while sparing prostatic growth.
Instead, we examined the androgen-regulated transcriptome, which are downstream of androgen receptor
activation in an effort to screen for proteins that may mediate androgen action on fat and muscle tissue. Prostate
tissues from the castrated animals either treated with testosterone or with follistatin were processed to isolate
mRNA. Transcription gene expression profiles are generated on the Affymetrix Mouse Geneome MG430 2.0
Arrays. Normalization was performed using the RMA method. [Irizarry, et al. 2003] The arrays were
background corrected, quantile normalized, then summarized using median polish. Simply plotting the
distribution of gene expression values can provide a general sense of array quality. Consistent with high quality
of processed data, the pattern includes a sharp peak at the lower expression values, typically around 4 to 5, then
a longer tail with an additional mode at around 9 to 10. It is assumed that a small portion of genes are expressed
at an appreciable measure, while the majority are lowly to not expressed and the two modes reflect this
assumption. Work on the Immgen project, where they have sampled 600 arrays, has shown that the bimodality
of the distribution is associated with higher quality input RNA.
Using the algorithm developed in our lab, Mode-of-Action by Network Inference (MNI), with our in-house
compiled mouse genome compendium, we have reverse-engineered the gene regulatory network for each of the
samples. The output of MNI provides us with a unique set of genes or a gene signature for each sample. The
genes identified or inferred by the MNI are genes that act as the key mediators of the sample’s unique gene
regulatory network. Thus, our MNI-inferred gene signatures are predicted to be mediators that are critical to the
underlying mechanism of testosterone or follistatin treatments. Based on these biological process analyses, we
have identified potential target genes of testosterone treatment in the prostate: Tram1(Src3), Nr4a2, Dvl1 and
Bmp6, and the potential target genes of follistatin treatment in the Levator Ani: Foxo1, Runx1, Pax9 and Prdm6
respectively. We are now working with our Endocrinologist collaborators to validation our MNI predicted state
mediator genes of their differential activation by testosterone and follistatin in mice. At the same time, we are
testing androgen signaling pathways in the prostate by silencing targeted androgen-dependent genes, and testing
the effect of testosterone on the resulting prostate cells. We are interrogating the same set of genes using
follistatin as a treatment, and compare the effect of follistatin vs. testosterone on the prostate cells. These
approaches allow us to validate our in silico predictions and identify the key pathways responsible for
follistatin’s anabolic effect on skeletal muscle. All the experimental validations are undergoing and a
manuscript based on the results are under preparation now.
At the same time we are also working with our Endocrinologist collaborators on the muscle dystrophic disease.
Given the emerging role of microRNAs in a variety of developmental processes, especially in patients with
muscular dystrophies, we determined whether the functional improvements observed with neonatal testosterone
administration in our SJL mice experiments were associated with alterations in the expression levels of the
microRNAs. Accordingly, we measured the expression of 72 microRNAs systematically. We find 28
microRNAs that are up-regulated in LGMD2B subjects were down-regulated by testosterone imprinting, while
35 microRNAs were unaffected by testosterone. To analyze the role of these dysregulated miRNAs playing in
the regulatory network, we performed pathway enrichment analysis. We found that the epigenetic intervention
by testosterone injection was associated with regulation of nine of the eleven pathways that are implicated in the
phenotypic manifestation of LGMD2B. Transcriptional regulation of representative genes in three pathways
(Wnt, TGF-beta and insulin signaling) predicted by the miRNA analysis was confirmed by qPCR based
Boston OAIC 2010 Annual Directory
profiling. These data indicate that testosterone imprinting induces specific alterations in the expression of
signaling pathways and microRNAs dysregulating in muscular dystrophies. Thus, an appropriately timed
testosterone pulse during early postnatal developmental window ameliorates disease phenotype and improves
physical function in adulthood in a mouse model of muscular dystrophy associated with dysferlin mutation. A
manuscript based on this study is under preparation now.
Developmental Project IV: Skeletal Muscle Precursors (SMPs)
Principal Investigator: Amy Wagers, Ph.D.
Upon the recommendation of the External Advisory Board and with the approval of the NIA staff, the Skeletal
Muscle Precursor Cell Core was converted into a developmental project. The objective of this developmental
project is to develop methods for reliable and consistent isolation of primary skeletal muscle progenitor cells
from the mice and humans to enable cutting-edge research related to muscle function and its deterioration
during aging. Muscle precursor cells are technically demanding to isolate and culture, and a high level of purity
and rigorous quality control is essential in generating reproducible data, particularly as the frequency and
function of these cells are known to fluctuate with age. Primary skeletal muscle cells are needed to study the
effects of host characteristics, including genetic abnormalities, disability, systemic treatments, age, and gender
on muscle differentiation and function.
Specific Aims:
1. To develop methods for the standardized isolation, expansion and culture of primary muscle cells
and muscle precursors from standard mouse strains
2. To develop and standardize methods for the differentiation of isolated muscle precursors by in vitro
culture
3. Standardize and validate methods for in vivo transplantation of muscle precursors and assessment of
engraftment function
4. To standardize methods for the optimal use of these cells in aging-related studies
STUDIES AND RESULTS: We have continued to update and innovate our methods to standardize the
procedures for isolation and enrichment of muscle precursor cells from mammalian skeletal muscle. We have
shown that Pax7 is a key regulator of skeletal muscle stem cells and is required along with Pax3 to generate
skeletal muscle precursors. We have identified a collection of genes induced by either Pax3 or Pax7 in C2C12
muscle cells. Two notable Pax3/7 targets are the inhibitory helix-loop-helix (HLH) proteins inhibitor of DNA
binding (Id) 2 and Id3, both of which are coordinately expressed with Pax7 in quiescent satellite cells and are
induced in quiescent C2C12 myogenic cells after ectopic expression of either Pax3 or Pax7. Ectopic Pax7
activates expression of a luciferase reporter driven by the Id3 promoter, and maximal induction of this reporter
requires a conserved Pax7 binding site located upstream of the Id3 gene. Chromatin immunoprecipitation
indicated that Pax7 is bound upstream of the Id3 promoter in quiescent satellite cells. In addition, short hairpin
RNA-mediated knockdown of Pax7 expression in cultured satellite cells coordinately decreased both Id2 and
Id3 expression. Together, these findings indicate that Id3 is a direct transcriptional target for Pax7 in quiescent
satellite cells, and they suggest that Pax7 acts to block premature differentiation of quiescent satellite cells by
inducing the expression of Id2 and Id3, which in turn may act to block either the precocious induction of
myogenic basic (b) HLH proteins, the activity of myogenic bHLH proteins, or both.
In the past year, we also have investigated the effects of various extracellular matrix (ECM) components on the
rate of proliferation and differentiation of muscle precursors and of new buffers for cell isolation on the
subsequent survival of isolated muscle precursor cells. These efforts have led to refined culture conditions that
more specifically address the experimental questions posed by individual users.
Boston OAIC 2010 Annual Directory
In addition, this year we began validation of methods for the in vivo transplantation of muscle precursors and
assessment of engraftment function that will provide additional important avenues for discovery for OAIC
investigators.
SIGNIFICANCE: Securing a reliable and consistent source of primary skeletal muscle progenitor cells and
their products is a major challenge in current studies to investigate the mechanisms of function promoting
therapies. The SMP developmental project provides standardized, validated cells for experimentation, and
reduces the per-experiment cost of cell purification by centralizing reagent and personnel costs. These efforts
significantly enhance the quality and reproducibility of the data generated in OAIC and related projects.
Pilot and Exploratory Studies Core (PESC)
Core Leader: Monty Montano, PhD
Telephone: (617) 414-4806
Fax: (617) 414-5280
E-Mail: [email protected]
Core Co-Leader: Shalender Bhasin, MD
Telephone: (617) 414-2950
Fax: (617) 638-8217
E-Mail: [email protected]
The overall goal of the Pilot and Exploratory Studies Core (PESC) is to support the expeditious translation of
early innovative research ideas ─ that have the potential for important discoveries but which carry a higher risk
premium than incremental science ─ into full-fledged projects by providing funding for:
1. Generation of early proof-of-concept preclinical efficacy data to determine the potential of novel targets
as function promoting anabolic therapies
2. Hypothesis-generating feasibility studies that are necessary for justifying greater investment in
definitive, larger studies
3. Exploratory mechanistic studies for target identification or for generation of specific hypotheses about
mechanisms by which function promoting anabolic therapies exert their effects on the skeletal muscle
4. Analysis of data acquired in ongoing or previous studies to explore hypotheses that may guide the
selection and design of future studies
5. Preliminary testing of interventions or research protocols in humans or animals for safety, feasibility, or
determination of optimal time course or dosage
As discussed below, even in its first six months since inception, each of the PESC projects has made substantive
progress towards achievement of its stated goals.
Currently funded Pilot/Exploratory Studies:
PESC Project I: Relationship between Muscle Function and Senescence Markers in HIV+ Older Women
Principal Investigator: Monty Montano, PhD
The goal of this pilot project is to determine the relationship between muscle size, muscle function and cellular
immune senescence (immunosenescence) in the context of HIV infection and treatment. To this end we are
recruiting two groups of HIV+ older women that differ in their history of nadir CD4 (less than 50 cells/mm3,
between 100-200 cells/mm3,), but currently share equivalent immune reconstitution (CD4 levels above 350
Boston OAIC 2010 Annual Directory
cells/mm3). In all subjects, virologic suppression will be an inclusion criteria. Our overall hypothesis is that
circulating markers for immune senescence will be associated with subclinical declines in muscle area and
physical function despite apparent CD4 T cell immune reconstitution. To date we have successfully mobilized
the laboratory of exercise physiology (a part of the Boston OAIC Pepper Center), and the Center for Infectious
Diseases to streamline enrollment and physical function testing.
The pilot project has enrolled about one third (20) of the subjects and interim analyses are in progress. The age
range is between 40-60 years and the nadir CD4 ranges are quite broad, with approximately half below 200
cells/ml and half above 200 cells/ml. All subjects have undergone a physical function assessment using the
SPPB and a loaded stair climb evaluation. Subjects are also assessed for psychosocial parameters designed to
evaluate stress in daily living. Various blood associated biomarkers are being measured and are likely to be
informative in association with physical function in this chronically burdened population.
We have also been conducting exploratory work based on existing specimens to identify markers for early
senescence in HIV infected subjects and have a manuscript in preparation, entitled “Premature expression of an
age-associated muscle senescence pathway in HIV infection.” This work was also accepted for presentation at
the Conference on Retroviruses and Opportunistic Infections (CROI), to be held in Boston in February, 2011.
Dr. Montano was also recently invited to give a seminar to describe some of this work on aging at a conference
in Philadelphia (Systems biology of Human Aging, Dec6-7, Drexel University).
PESC Pilot II: Mechanism-Based Drug Discovery: Anabolic Effects of a follistatin (BJS1), on Skeletal
Muscle Mass and Physical Function in Older Mice
Principal Investigator: Ravi Jasuja, PhD
Endogenous androgens (testosterone, T and dihydrotestosterone, DHT) play an important role in development
and maintenance of muscle and bone health in males. Unfortunately, DHT and T stimulate prostate (normal and
cancerous) tissue and therefore, androgen androgen supplementation in older adults is not widely prescribed.
Androgen deprived state results in severe loss in bone and muscle mass with a concomitant increase in fat mass.
In preliminary studies with young castrated mice, recombinant BJS1 (follistatin, Fst) treatment restores the
castration-induced loss of bone mineral density and skeletal muscle mass. Therefore, we proposed to examine if
these anabolic effects will restore the age associated loss in muscle mass in old mice without the stimulation of
prostate tissue. Consistent with the proposed hypothesis, we find that FST does not stimulate the benign (invivo and in-vitro) or prostate cancer cells. Our initial attempts with the infusion were partially successful due to
clogging of osmotic pumps and therefore preventing the effective protein delivery. As an alternative, we have
recently begun the experiments with twice daily injections subcutaneously to pursue the final set of proposed
experiments.
Background: Numerous studies have established that androgens given to adult men with acquired
hypogonadism reduce bone remodeling, increase trebecular bone density and increase lean muscle mass.
Similarly, chemically-induced hypogonadism (androgen deprivation therapy, ADT), for treating prostate cancer,
is also associated with loss of bone mass, muscle mass, fractures, and disability. Although these anabolic
manifestations of circulating androgens are well documented, concerns about prostatic side effects (benign and
cancerous) have limited the enthusiasm about their clinical use as an anabolic therapy. Therefore, there is an
enormous unmet need for function promoting anabolic therapies that improve bone and skeletal muscle mass
without the risk of promoting the prostate growth. Through microarray analysis of androgen-regulated genes,
we have identified a signaling molecule (BJS1 or follistatin) that is activated by testosterone and DHT. In
preliminary studies with young castrated mice, recombinant follistatin treatment restores the castration-induced
loss of bone mineral density and skeletal muscle mass. The overall goal of this pilot project is to conduct proofof-principle preclinical studies to establish that follistatin promotes bone anabolism without the stimulation of
normal prostate and prostatic tumors.
Boston OAIC 2010 Annual Directory
Accordingly, we tested the following two hypotheses in this project:
Hypothesis 1: Follistatin supplementation in old mice increases skeletal muscle mass and decreases fat mass
without inducing an increase in prostate mass over and above that expected from change in whole body mass.
Hypothesis 2: Follistatin exerts pro-myogenic and anti-adipogenic effects independent of androgen receptor
signaling.
Specific Aims:
Specific Aim 1: To determine the dose-dependent effects of follistatin on skeletal muscle and fat mass, muscle
strength, and physical function in intact old mice and assess whether the anabolic effects of follistatin
administration observed at two weeks are maintained during long term follistatin infusion for eight weeks.
Specific Aim 2: To determine whether the effects of follistatin supplementation on skeletal muscle mass and
strength are independent of androgen receptor signaling and are exerted without affecting the growth of prostate
gland
Experimental summary: In the past year, in order to examine the mechanisms underlying prostate specific
differential effects of folistatin, systems biology analysis was conducted on mRNA regulation in these tissues.
PESC Project III: The Role of Testosterone in the Regeneration of Young and Aged Skeletal Muscles and
the Synergy with the Notch and TGF-β Pathways.
Principal Investigator: Carlo Serra, PhD
The main goal of this project is to explore if testosterone treatment ameliorates the regeneration of both young
and aged skeletal muscles, and if the Notch and transforming growth factor-b (TGF-b) signaling modulate this
effect. The experiments will be conducted in vivo, on injured and uninjured skeletal muscles of mice of various
ages and in vitro, by using mouse muscle satellite cells and fibers. Mice will be treated with or without
testosterone, and its effects on muscle regeneration will be assessed by immunohistochemical means, gene
expression profiles and signaling analysis. The new information gathered from this project will provide critical
inputs to better define an androgen-based pharmacological strategy aimed to counteract the progressive skeletal
muscle atrophy associated with human aging.
During the last year we investigated the effect of testosterone on the skeletal muscle regeneration in old mice.
In vivo experiments: 24 month-old male mice were subdivided in three experimental groups; sham-operated
(Sham), castrated (Cast) and castrated supplemented with testosterone (Cast-T). We treated the mice according
with the proposed experimental plan. We noticed a high index of mortality after castration. Body weight was
significantly reduced in Cast mice compared to Sham, and testosterone supplementation rescued this value.
After 4 days from injury in the tibialis anterior muscle, Cast-T mice shown an increased number and size of
regenerating fibers, compared to Sham and Cast mice. Moreover, Cast-T mice showed increased number of
satellite cells in the uninjured tibialis anterior muscle after 3 weeks of testosterone treatment. As expected, the
androgen-dependent levator ani muscle was atrophied in Cast mice, and its mass ad satellite cell number was
totally rescued in Cast-T mice. Overall, these data indicate that testosterone sustains muscle regeneration in old
mice, as previously found in young mice, and confirm the potential use of testosterone supplementation to
enhance muscle regeneration in aged muscle.
We are performing the last assays to determine number and distribution of proliferating satellite cells after 2 and
3 days from muscle injury, and to evaluate testosterone’s effect on the Notch pathway using human primary
myoblasts in vitro. Once completed these experiments in the next few weeks, we will submit the paper.
PESC Project IV: Physical Function and Metabolic Parameters in Elderly Men Who Have OpioidInduced Hypogonadism
Boston OAIC 2010 Annual Directory
PI: Shehzad Basaria, MD
The treatment of pain has received increasing attention over the past decade. Many have labeled pain as the “5th
vital sign” and questioning about pain has become a common practice in medical clinics. Data suggest that the
prevalence of chronic non-cancer pain is common and affects up to 15-30% of the US population. A recent
survey showed that prescription of potent opioids have increased significantly with 5.9 million prescriptions
given to patients with chronic pain in 2000 compared to 1.3 million in 1980. Pharmacy claims data show that
older patients have more claims for opioid analgesics than younger subjects, suggesting that the consumption of
opioids have significantly increased in the elderly population.
Testosterone levels decline with natural aging. About 20-50% of men >60 years old have testosterone levels
that are lower than levels seen in young men. To make matters worse, hypogonadism is a known complication
of opioid use. Indeed, men on opioids have been shown to have very low testosterone levels, sometimes
reaching castrate levels. This suggests that older men on opioids are at risk of developing more profound
hypogonadism. The prevalence of hypogonadism in men on opioids is about 75%, with estimates suggesting
that approximately 5 million men in the US have opioid-induced hypogonadism. These men have higher
prevalence of sexual dysfunction, decreased quality of life (QOL) and osteoporosis. A recent study showed that
sexual function and QOL improves on testosterone therapy. However, no information exists on body
composition, physical function or cardiovascular (CV) risk factors in these men.
Recent data show that low testosterone in men is an independent risk factor for diabetes, metabolic syndrome
and cardiovascular mortality. These CV complications are seen even in men who have testosterone levels that
are slightly below the normal range. Since men on opioids have very low testosterone levels, this may
predispose them to even higher metabolic burden. To make matters worse, opioids themselves have been
associated with insulin resistance, diabetes and hyperlipidemia irrespective of testosterone levels. Indeed, a
recent large study showed that opiates are an independent risk factor for coronary artery disease and the amount
of opiate consumption is directly associated with the degree of coronary atherosclerosis. Hence, it is possible
that opiates increase a subject’s CV risk directly (due to their drug effect) and indirectly by inducing
hypogonadism.
The goal of this pilot study is to evaluate the prevalence of adverse body composition, physical function and
cardiovascular risk factors in men ≥60 years who are taking opioids for >6 months.
PESC Project V: Defective ankle joint performance and myostatin deficiency
Principal Investigator: Wen Guo, PhD
Background: Sarcopenia is a progressive age-related loss of skeletal muscle mass and strength. Myostatin, a
member of the TGF-beta family, has been identified as a powerful inhibitor of muscle growth. Absence or
blockade of myostatin induces massive skeletal muscle hypertrophy and reduces age-related sarcopenia.
Blocking myostatin in aged mice increases lipid oxidation and improved insulin sensitivity. All these make
myostatin inhibitors promising therapeutic tools for treatment of age-related muscle loss to improve the quality
of life of the elderly. Few investigations have reported side effects of myostatin deficiency, especially in aged
animals or humans. On the other hand, increasing evidence now shows that although skeletal muscle remains
the most prominent site of myostatin actions, other tissues including cardiac muscle, tendon, bone, joints, and
the brain, are also subjected to myostatin regulations. In particular, knockout of myostatin results in smaller and
stiffer tendons. As elderly people are one of the major targets for pharmacological myostatin interventions, it is
important to determine how this tendon effect, and other possible side effects, may adversely affect physical
performance in aged individuals.
We recently noticed a unique pattern of talocrural (ankle) joint locking in myostatin null mice that were middle
age (10 - 15 mo), with no gross abnormalities found in the age-matched wild-type or younger myostatin null
animals. The diseased ankles are also characterized by visually detectable swelling. This was a fortuitous
Boston OAIC 2010 Annual Directory
discovery made in animals that remained from other experiments. Much additional work is needed to determine
the nature of this finding and its physiological significance. We propose this pilot application in order to obtain
the seed money that will allow us to perform additional preliminary studies that are needed for NIH funded
mechanism investigations and clinical trials.
Specific aims:
Aim-1. To determine the kinetics of ankle locking with aging and effects of myostatin deficiency. In this
aim, we will generate a large cohort of animals and regularly monitor the time course when signs of restricted
motion in the hind ankle develop. Myostatin activity will be manipulated using the following strategies:
♦
♦
♦
constitutive gene deletion,
doxycycline-induced expression of mstn inhibitory propeptides in mice with transgenic expression of
tetracycline responsive propeptide mutant at young, middle, and late adult age,
adenovirus-associated virus mediated expression of mstn inhibitory propeptides in wild-type mice at
young, middle, and late adult age,
Beginning at 3 mo of age, we will monitor the range of motion manually on a weekly basis. Synovial
impingement, bone and soft tissue degeneration, tendon/ligament erosion, and joint capsule orientation and
thickness will be monitored by MRI at a monthly basis. For each tested group that displays ankle joint locking,
the effects of mstn on mechanical performance will be measured on isolated tendons, ligaments, and cartilages
of affected joints before and after the ankle flexibility is compromised.
Aim-2. To test the mechanism that causes ankle locking with age in mice with mstn deficiency. We
propose to investigate the following possibilities that myostatin inhibition may cause restriction of ankle
motions by:
♦
♦
♦
♦
specific defects in joint capsule integrations, such as mismatched muscle hypertrophy and limited size or
function of tendon, ligament, and cartilage.
accelerated immunosenescence that leads to early on-set of joint osteoarthritis and synovial inflammation,
altered plasma profile for growth factors and cytokines that accelerates aging-associated joint inflammation
muscle hypertrophy causes excessive hypoxia in the joint which induces ER stress and synoviolin
expression.
We will distinguish these pathways by histology and immunohistochemistry on different tissue components of
the joint capsule, and determine the different impacts caused by different protocols for mstn inhibition as
described in Aim-1. To assess the association with systemic inflammation status, immunocyte activities in
lymph nodes and spleen will also be determined by immunohistochemistry in correlation with plasma cytokine
profile. To determine whether mstn deficiency aggravates hypoxia in the joint, synovia tissue will be used to
analyze ER stress marker XBP-1 and synoviolin by Western analysis and real-time PCR. In addition, samples
will be collected from joints of other anatomic sites such as the knees and fingers of both front and hind legs to
determine whether mstn deficiency associated malfunction in aged animals occurs only at the hind ankle or can
be more widely spread throughout the body.
PESC Project VI: Dietary Protein and Functional Decline in the Framingham Offspring Study
Principal Investigator: Lynn Moore, Ph.D.
The proposed specific aims for this project were to complete the following analyses in the Framingham
Offspring Study: (1) to estimate the independent effects of the amount, type (various animal vs. plant sources),
and sources (e.g., dairy, red meat, soy) of dietary protein on the risk of functional decline in adults over the age
of 55 years; (2) to determine whether the above protein effects are independent of or modified by the type and
Boston OAIC 2010 Annual Directory
amount dietary fats consumed; (3) to determine whether the effects of dietary protein are modified by other risk
factors for functional decline (especially physical activity levels, BMI, smoking status, other dietary patterns);
and (4) to determine the extent to which the effects of these dietary protein exposures on the above outcomes
are mediated through intermediate health effects including such as diabetes or cardiovascular disease.
The first steps toward accomplishing the above objectives involve the creation of analysis data sets. The dietary
data that we are using in this study are from diet records that were collected during examination years 3 and 5.
These data were entered previously into the Nutrition Data System of the University of Minnesota for nutrient
analysis. Through that analysis, we are able to separate animal from vegetable proteins. We also have data on
the following individual amino acids: tryptophan, threonine, isoleucine, leucine, lysine, methionine, cystine,
phenylalanine, tyrosine, valine, arginine, histidine, alanine, aspartic acid, glutamic acid, glycine, proline, and
serine. The branched-chain amino acids (leucine, isoleucine and valine) are of particular interest to this topic.
It is possible that the food sources of protein and various amino acids may be more important predictors of
functionally-related outcomes than protein or individual amino acids themselves. Therefore, we have linked the
food ingredient data from the NDS output with codes from the USDA’s “MyPyramid Equivalents Database for
USDA Survey Food Codes, 1994-2002, Version 1”. Thus, our data set now includes important individual
protein food sources including dairy, red meats, poultry, fish, eggs, legumes, and nuts and seeds. Finally, due to
the close association between protein and dietary fats, we have included all dietary fats and fatty acids in our
data set.
We have parameterized the functional status variables of interest to this analysis and we are currently awaiting
receipt of some of these variables from the data management staff in Framingham. These variables relate to six
different functional status domains—basic ADLs, instrumental ADLs, mobility, endurance and strength.
PESC Project VII: Cognitive and Functional Correlates of Minimally-Invasive Coronary Artery Bypass
Graft (CABG) Surgery
Principal Investigator: Angela L. Jefferson, PhD
The study, which is in collaboration with Dr. Robert Poston, Chief of Cardiothoracic Surgery at Boston Medical
Center, compares cognitive and functional outcomes of patients undergoing minimally invasive versus
traditional open-heart CABG
Table 1. Neuropsychological Protocol & Change Results
procedures. Minimally
invasive CABG involves the
Open
Mini
Test
d
p
M±SD
M±SD
use of a robotic surgical
technique that is less invasive
-1.0±1.1 -1.3±1.9 0.2 0.70
Mini Mental State Exam
than traditional CABG and
0.5 0.36
California Verbal Learning Test-II Long Delay 2.4±1.9 1.5±1.7
may yield better post-operative Recall
cognitive and functional
-1.2±6.2 -1.1±4.9 -0.01 0.98
Animal Naming
†
results. The project is a unique
Trail Making Test, Part A
-8.7±12.4 6.5±11.9 -1.3 0.03*
opportunity to explore the
Trail Making Test, Part B†
-9.2±39.9 8.1±35.6 -0.5 0.40
potential cognitive and
4.0±3.8 -2.4±8.6 1.0 0.10
Digit Symbol Coding
functional benefits of a
2.4±19.3 -5.5±10.2 0.5 0.26
Color-Word Interference
cutting-edge surgical
-5.0±56.8 -30.0±31.2 0.55 0.50
SF-36-Physical Functioning
technique that may benefit
Note. Unadjusted values presented as M±SD where M=mean change in raw scores as
future older Americans
determined by raw score at time2 minus raw score at time1; Negative values=postundergoing cardiac surgery.
operative decline; †=timed tasks, so positive values reflect post-operative decline;
*=significant between-group difference; d=Cohen’s effect size
The specific aim of this pilot project is to test the hypothesis that minimally-invasive coronary artery bypass
surgery will be associated with lower rates of cognitive and functional decline than the standard coronary artery
bypass surgery.
Boston OAIC 2010 Annual Directory
All recruitment for the current pilot study has ended and data is currently being analyzed. Preliminary results
suggest differential short-term cognitive outcomes for patients undergoing traditional and robotic CABG. As
seen in the Table 1, participants who underwent the traditional (open) CABG procedure performed significantly
better on Trail Making Test, Part A than robotic (mini) CABG patients. In general, though not statistically
significant, raw data and effect size information suggest participants who underwent the robotic CABG
procedure had worse short-term (i.e., 12 week) neuropsychological outcomes as compared to participants who
underwent traditional CABG surgery. Post-hoc, a number of possible mediating factors for this outcome,
including ejection fraction, creatinine, and vascular risk factors, were taken into account but failed to provide an
explanation for the findings. In contrast, inclusion of changes in self-perceived health status (from the SF-36)
did attenuate the findings (p=0.12). That is, robotic CABG patients declined substantially in their postprocedure self-reported health status as compared to the traditional CABG patients. Unfortunately, the sample
size for this pilot project is very small and the departure of the cardiothoracic surgeon responsible for the
robotic procedure (i.e., Dr. Robert Poston) does not permit additional data collection to enhance the sample
sizes for each group. However, the preliminary results raise interesting questions regarding cognitive outcomes
for older adults following different types of bypass surgery.
PESC Project VIII: Role of skeletal muscle stem cells in age-related muscle dysfunction
Principal Investigator: Simone Hettmer, MD
Abstract: Skeletal muscle accounts for up to nearly 50% of human body mass and allows for locomotion by
transmitting the ontractile forces, which move our bodies. Lifelong maintenance of skeletal muscle function
relies critically on preserving the regenerative capacity of muscle fibers through a highly regulated process that
begins with activation of normally quiescent muscle satellite cells. Satellite cells are located beneath the basal
lamina of mature muscle fibers and contain a heterogeneous pool of myogenic precursor cells. In mice,
combinatorial analysis of multiple cell surface markers allows direct discrimination and isolation by
fluorescence-activated cell sorting (FACS) of a distinct population of highly regenerative muscle stem cells,
called skeletal muscle precursor cells (SMPs), from the satellite cell pool. However, such cell sorting strategies
to isolate analogous populations of human skeletal muscle stem cells have yet to be developed. The goal of this
proposed work is to establish robust methodologies for the prospective isolation and functional assessment of
human skeletal muscle precursor cells (hSMPs), and use these to test whether deficits in this population are
responsible for limiting muscle regenerative activity in aged individuals. Pharmacological reversal of deficient
hSMP function in aged muscle may, ultimately, lead to novel strategies to promote healthy muscle function into
old age.
Background and preliminary findings: This proposed work builds on the concept that human muscle function
is maintained by a normally quiescent subset of skeletal muscle stem cells, contained within the pool of muscle
satellite cells and marked by expression of the paired-box transcription factor PAX7. These muscle stem cells
respond to regenerative cues, such as exercise or injury, by proliferating to form myoblasts, which terminally
differentiate and fuse to generate multinucleated myotubes. Exhaustion of muscle satellite cells has been
implicated in the loss of muscle mass and function (sarcopenia) which typically occurs with increasing age and
is a major contributor to the development of frailty. Sarcopenia limits functional performance and, therefore,
independence in affected individuals. Our preliminary experiments in mice demonstrate that muscle stem cell
frequency and function decline with age, and that this decline contributes directly to impaired regenerative
capacity in aged muscle. Here, we hypothesize that dysfunction of the skeletal muscle precursor cell population
likewise contributes significantly to compromised homeostasis in the muscle of aged humans.
As a prerequisite to identifying and ultimately reversing the particular functional deficits that may be present
within the muscle precursor cell pool of aged humans, we have set out to define specific strategies to isolate this
population from human skeletal muscle. In our ongoing, preliminary experiments, we have adapted wellestablished protocols for the isolation of myofiber-associated (MFA) cells from mouse skeletal muscle to isolate
a similar subset of MFA cells from fresh, non-fixed human adult and fetal muscle. We also have established
Boston OAIC 2010 Annual Directory
conditions to induce in vitro formation of myosin heavy chain expressing, multinucleated myofibers from
isolated human MFA cells. Finally, we have identified several cell surface antigens, including CD45, MAC1,
Glycophorin, CD31, CD34, CD90, CD56 and Integrin alpha 7, that are expressed by human MFA cells and can
sub-divide the muscle precursor cell pool. Importantly, using both real-time PCR and immunocytochemical
staining, we have demonstrated that all Pax7-expressing cells in muscle are contained within the MAC1-CD45CD34- subset of human MFA cells, while MAC1-CD45-CD34+ cells are PAX7 negative. Because PAX7 is a
specific marker of muscle regenerative cells, enrichment of PAX7+ cells within the MAC1- CD45-CD34subset of human MFA cells suggests that this subset of cells contains the skeletal muscle stem cell population.
To validate the regenerative function of these cells, we recently established conditions to detect transplanted
human cells engrafted in mouse muscle by species-specific staining for the human nuclear antigen Lamin A/C
and the human membrane-associated antigen Spectrin.
Hypothesis and research plan: We propose here that the postnatal growth, repair and maintenance of human
skeletal muscle depends on a specialized subset of myofiber-associated muscle stem cells whose function is
impaired in aged muscle, and that reversal of this impairment will improve the regenerative capacity and
physical function of aging individuals. To test this hypothesis, we propose two specific aims:
Aim 1: Identify the unique combination of cell surface antigens that permits prospective isolation of human
skeletal muscle stem cells able to give rise to selectively myogenic colonies in vitro and to generate new
muscle fibers and additional skeletal muscle precursors in vivo.
Our preliminary experiments (obtained using fetal skeletal muscle provided by Advanced Bioscience Resources
Inc., Alameda, CA) indicate that MAC1-CD45-CD34- MFA cells are enriched for the human skeletal muscle
stem cells. However, this population is still contaminated by non-myogenic, PAX7 negative cells. To obtain a
pure population of human skeletal muscle stem cells, we will further sub-fractionate MFA cells from human
skeletal muscle, using additional candidate cell surface markers, by FACS sorting available through the Boston
Pepper Center Muscle Progenitor Cell Core. Using protocols established in our previous experiments, sorted
populations will be tested for (1) enrichment of PAX7, a canonical satellite cell marker, (2) myogenic colony
formation in culture, and (3) in vivo regenerative potential, assessed by the ability to form new muscle fibers
after injection into the gastrocnemius muscles of NOD/SCID Il2rg-/- (NOG) mice. NOG mice are severely
immunodeficient, which prevents immune rejection of implanted human cells. Human myogenic engraftment
will be evaluated by species specific staining of frozen sections for Lamin A/C and Spectrin in host muscle
harvested one month after injection. Costaining for muscle differentiation markers (MyoD, Myogenin, Desmin)
will test whether engrafted cells can differentiate appropriately in vivo, and PAX7 staining will assess the
engrafted cells’ ability to self-renew and repopulate the satellite cell pool. These experiments will establish
protocols to isolate bona fide human skeletal muscle stem cells (hSMPs) capable of differentiation and selfrenewal.
Aim 2: Identify novel targets for potential therapeutic intervention to reverse changes in the frequency and
function of skeletal muscle stem cells isolated from aged, healthy human donors compared to muscle stem
cells from young, healthy human donors.
hSMPs will be prospectively isolated from skeletal muscle of young (20 to 30 years old) and aged (65 to 80
years old), healthy individuals. Muscle specimens will be obtained in collaboration with Dr. Roger Fielding
under IRB-approved informed consent by needle biopsy of the vastus lateralis muscle, and hSMPs will be
isolated using methods established and validated in Aim 1 of this proposal. In initial experiments, we will
determine differences in the frequency of skeletal muscle stem cells, in their ability to initiate myogenesis in in
vitro clonal assays, and to engraft in vivo in the pre-injured extremity muscles of immunodeficient mice to
generate new muscle fibers and skeletal muscle precursors. Based on previous studies and on our preliminary
studies in young vs. aged mice, we expect that these experiments will confirm changes in human skeletal
muscle stem cell frequency and function with increasing age. We will then perform genome-scale expression
Boston OAIC 2010 Annual Directory
profiling to identify differentially expressed molecules in young vs. aged human muscle stem cells to identify
candidate pathways for therapeutic intervention. We will test candidate small molecule compounds, including
compounds implicated by our preliminary studies in mice as regulating mouse muscle stem cell function with
age, to test whether they have efficacy in enhancing human muscle stem cell function. These candidate
pathways include inhibitors of the NF-kB, TGF-beta, and TOR pathways and activators of the Notch and Wnt
signaling pathways. Taken together, these studies will reveal fundamental insights into the human muscle
regenerative process and how that process is altered with age, and we expect that findings from this work will
suggest novel targets for therapeutic intervention to slow or reverse age-associated muscle wasting and
functional decline.
Section III: Collaborative Grants Awarded to Boston OAIC Investigators
The past year has witnessed very substantial collaboration among Boston OAIC’s investigators in developing a
number of NIH grant applications.
•
Drs. Fielding and Jette received funding for the LIFE Trial, of which Tufts-NEMC/HNRCA is a part.
•
Drs. Bhasin, Storer, Fielding, Jette, and Kiel received funding for the T Trials, of which BU is a part.
•
Dr. Lisa Ceglia, an RCDC awardee, has recently received K12 grant funding. She is mentored jointly by
Drs. Fielding and Dawson-Hughes.
•
Dr. James Collins received a Howard Hughes Investigator award.
•
Drs. Bhasin, Ramachandran, and Murabito have received an RO1 grant from NIA to determine populationbased normative ranges for testosterone in men using the Framingham Heart Study samples.
•
Drs. Bhasin, Storer, Basaria, and Fielding are co-investigators on a recently funded NIA grant to investigate
the effects of testosterone on physical, sexual, cognitive function and vitality in older men (The T Trials).
•
Drs. Bhasin, Guo, and Jasuja have received an NIH RO1 grant to investigate the mechanisms of myostatin
action on mesenchymal stem cell differentiation.
•
Drs. Andre Araujo and John McKinlay received funding for the BACH-BONE Study; Drs. Bhasin and
Storer are co-investigators on this project, which will be a new user of the Function Assessment Core.
•
Drs. Wagenaar, Bhasin, Jette, and Felson submitted an S10 application for establishing a Laboratory for
Assessment of Gait Quality.
•
Drs. Bhasin, Storer, and Jette submitted a grant application to investigate the “Effects of vitamin D
Supplementation on Physical Function in Older Individuals with Mobility Limitation”.
•
Drs. Bhasin, Wagers, Jasuja, and Guo received funding for the competing continuation of their funded RO1
grant on “Mechanisms of Androgen Action.”
•
Drs. Jette, Wagenaar, Friedman, and Silliman submitted an application to establish a Royball Center at BU.
•
Dr. Fielding received funding for a grant entitled: “Efficacy of whey protein supplementation on resistance
exercise-induced changes in muscle strength, fat free mass, and function in mobility-limited older adults”
from the National Dairy Council.
•
Drs. Fielding and Dawson-Hughes submitted an R21 application to the NIA entitled: “Bicarbonate effects
on skeletal muscle in older post-menopausal women”.
•
Drs. Serra and Wagers submitted a grant to Smith Foundation to study mechanisms by which circulating
stem cells can hone into the skeletal muscle.
•
Drs. Bhasin, Apovian, Storer, Jette, and Moore received funding for their grant application titled
“Optimizing Protein Intake in Older Americans with Mobility Limitations” to investigate the optimal
protein requirements for anabolic balance in older Americans.
Boston OAIC 2010 Annual Directory
•
Drs. Bhasin, Basaria, Bachman, and Storer received a grant from Ligand Pharmaceuticals to conduct a pilot
study of the effects of a novel nonsteroidal SARM on muscle mass and strength in humans.
•
Drs Bhasin, Fielding, Jette, Storer, Serra, Latham, Montano, Jasuja, Bachman, Basaria and Travison have
collaborated to submit a program project (P01) grant application to NIA on “Translating Muscle Mass and
Strength gains into Functional Improvements.”
•
Dr. Jette received funding from NIH for his R24 application to establish the Boston Rehabilitation
Outcomes Center. Dr. Fielding is a collaborator on this grant.
•
Dr. Guo submitted an R21 grant application to NIA on Healthy aging and myostatin antagonists and
received a 5th percentile score.
•
Dr. Ceglia received a KL2 Research Career Development Award from Tufts University CTSI.
•
Dr. Friedman received an NCRR CTSA supplement for “Research Workforce Development: Informatics
Training for Social and Behavioral Scientists Engaged in Clinical and Translational Research.
•
Dr. Jefferson received funding from NIA for her grant titled “Ethnic Differences Among Research
Subjects in Willingness to Assent to Brain Donation.”
•
Dr. Jefferson received funding for the Boston University Alzheimer’s Disease Center PAIRS Program
from the Kenneth B. Schwartz Center.
•
Dr. Wagenaar received a grant titled Continuous Monitoring of Functional Activities and Movement
Disorders in Individuals with Parkinson’s Disease from the Coulter Translational Partners Program.
•
Dr. Wagenaar’s R01 grant application for Effects of Parkinson’s Disease on Perception, Cognition and
Gait was funded by NIH.
•
Dr. Wang received R01 funding from NIH for her grant application titled Tai Chi and Knee
Osteoarthritis.
•
Dr. White was awarded a Geriatric Research Grant from the Foundation for Physical Therapy of the
American Physical Therapy Association.
•
Dr. White received a Rheumatology Investigator Award from the Research and Education Foundation of
the American College of Rheumatology.
•
Dr. Rivas has submitted a grant based on preliminary data collected from this OAIC Diversity Supplement
Grant.
•
Dr. Devyani Misra received an Arthritis Foundation Clinical Research to Transition Award (CRTA) for her
application titled “Associated of Knee Osteoarthritis and Frailty.”
Section IV: Publications
Publications by Boston OAIC Investigators
1. Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd, Birnbaum NS, Burmester GR,
Bykerk VP, Cohen MD, Combe B, Costenbader KH, Dougados M, Emery P, Ferraccioli G, Hazes JM,
Hobbs K, Huizinga TW, Kavanaugh A, Kay J, Kvien TK, Laing T, Mease P, Ménard HA, Moreland LW,
Naden RL, Pincus T, Smolen JS, Stanislawska-Biernat E, Symmons D, Tak PP, Upchurch KS, Vencovsky
J, Wolfe F, Hawker G. 2010 rheumatoid arthritis classification criteria: an American College of
Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis. 2010
Sep;69(9):1580-8. PMCID: In Process.
2. Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd, Birnbaum NS, Burmester GR,
Bykerk VP, Cohen MD, Combe B, Costenbader KH, Dougados M, Emery P, Ferraccioli G, Hazes JM,
Hobbs K, Huizinga TW, Kavanaugh A, Kay J, Kvien TK, Laing T, Mease P, Ménard HA, Moreland LW,
Boston OAIC 2010 Annual Directory
Naden RL, Pincus T, Smolen JS, Stanislawska-Biernat E, Symmons D, Tak PP, Upchurch KS, Vencovský
J, Wolfe F, Hawker G. 2010 Rheumatoid arthritis classification criteria: an American College of
Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010
Sep;62(9):2569-81. PMCID: In Process.
3. Allison KR, Collins JJ. Bacteria as control engineers. Mol Cell. 2011 Jan 7;41(1):4-5. PMCID: In Process.
4. Araujo AB, Hall SA, Ganz P, Chiu GR, Rosen RC, Kupelian V, Travison TG, McKinlay JB. Does erectile
dysfunction contribute to cardiovascular disease risk prediction beyond the Framingham risk score? J Am
Coll Cardiol. 2010 Jan 26;55(4):350-6. PMCID: PMC2845313. PMCID: In Process.
5. Atz AM, Travison TG, Williams IA, Pearson GD, Laussen PC, Mahle WT, Cook AL, Kirsh JA, Sklansky
M, Khaikin S, Goldberg C, Frommelt M, Krawczeski C, Puchalski MD, Jacobs JP, Baffa JM, Rychik J,
Ohye RG; Pediatric Heart Network Investigators. Prenatal diagnosis and risk factors for preoperative death
in neonates with single right ventricle and systemic outflow obstruction: Screening data from the Pediatric
Heart Network Single Ventricle Reconstruction Trial. J Thorac Cardiovasc Surg. 2010 Jun 17. [Epub ahead
of print]. PMCID: In Process.
6. Bachman ES. A school-based intervention for diabetes risk reduction. N Engl J Med. 2010 Oct
28;363(18):1769; author reply 1770.
7. Bachman E, Feng R, Travison T, Li M, Olbina G, Ostland V, Ulloor J, Zhang A, Basaria S, Ganz T,
Westerman M, Bhasin S. Testosterone Suppresses Hepcidin in Men: A Potential Mechanism for
Testosterone-Induced Erythrocytosis. J Clin Endocrinol Metab. 2010 Oct;95(10):4743-7. Epub 2010 Jul 21.
PMCID: In Process.
8. Basaria S. Androgen abuse in athletes: detection and consequences. J Clin Endocrinol Metab. 2010
Apr;95(4):1533-43. Epub 2010 Feb 5. PMCID: In Process.
9. Basaria S, Coviello AD, Travison TG, Storer TW, Farwell WR, Jette AM, Eder R, Tennstedt S, Ulloor J,
Zhang A, Choong K, Lakshman KM, Mazer NA, Miciek R, Krasnoff J, Elmi A, Knapp PE, Brooks B,
Appleman E, Aggarwal S, Bhasin G, Hede-Brierley L, Bhatia A, Collins L, LeBrasseur N, Fiore LD,
Bhasin S. Adverse events associated with testosterone administration. N Engl J Med. 2010 Jul
8;363(2):109-22. Epub 2010 Jun 30. PMCID: In Process.
10. Berman AH, Farzanfar R, Kristiansson M, Carlbring P, Friedman RH. Design and Development of a
Telephone-Linked Care (TLC) System to Reduce Impulsivity among Violent Forensic Outpatients and
Probationers. J Med Syst. 2010 Aug 19. [Epub ahead of print]. PMCID: In Process.
11. Bhasin S. The brave new world of function-promoting anabolic therapies: testosterone and frailty. J Clin
Endocrinol Metab. 2010 Feb;95(2):509-11. PMCID: In Process.
12. Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, Montori VM; Task
Force, Endocrine Society. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine
Society clinical practice guideline. J Clin Endocrinol Metab. 2010 Jun;95(6):2536-59. PMCID: In Process.
13. Bhasin S, Matsumoto AM. Patient information page from The Hormone Foundation. Patient guide to
testosterone therapy in adult men with androgen deficiency syndromes. J Clin Endocrinol Metab. 2010
Jun;95(6):2p following 3085. PMCID: In Process.
14. Bird D, Oldenburg B, Cassimatis M, Russell A, Ash S, Courtney MD, Scuffham PA, Stewart I, Wootton R,
Friedman RH. Randomised controlled trial of an automated, interactive telephone intervention to improve
type 2 diabetes self-management (Telephone-Linked Care Diabetes Project): study protocol. BMC Public
Health. 2010 Oct 12;10:599. PMCID: PMC296462
15. Bixby SD, Hettmer S, Taylor GA, Voss SD. Synovial sarcoma in children: imaging features and common
benign mimics. AJR Am J Roentgenol. 2010 Oct;195(4):1026-32. PMCID: In Process.
16. Bosco JL, Silliman RA, Thwin SS, Geiger AM, Buist DS, Prout MN, Yood MU, Haque R, Wei F, Lash TL.
A most stubborn bias: no adjustment method fully resolves confounding by indication in observational
studies. J Clin Epidemiol. 2010 Jan;63(1):64-74. Epub 2009 May 19. PMCID: PMC2789188.
Boston OAIC 2010 Annual Directory
17. Bradlee ML, Singer MR, Qureshi MM, Moore LL. Food group intake and central obesity among children
and adolescents in the Third National Health and Nutrition Examination Survey (NHANES III). Public
Health Nutr. 2010 Jun;13(6):797-805. Epub 2009 Sep 22. PMCID: In Process.
18. Callura JM, Dwyer DJ, Isaacs FJ, Cantor CR, Collins JJ. Tracking, tuning, and terminating microbial
physiology using synthetic riboregulators. Proc Natl Acad Sci U S A. 2010 Sep 7;107(36):15898-903. Epub
2010 Aug 16. PMCID: PMC293662
19. Carabello RJ, Reid KF, Clark DJ, Phillips EM, Fielding RA. Lower extremity strength and power
asymmetry assessment in healthy and mobility-limited populations: reliability and association with physical
functioning. Aging Clin Exp Res. 2010 Aug;22(4):324-9. Epub 2009 Nov 25. PMCID: In Process.
20. Ceglia L, Abrams SA, Harris SS, Rasmussen HM, Dallal GE, Dawson-Hughes B. A simple single serum
method to measure fractional calcium absorption using dual stable isotopes. Exp Clin Endocrinol Diabetes.
2010 Oct;118(9):653-6. Epub 2009 Oct 23. PMCID: In Process.
21. Ceglia L, Abrams SA, Harris SS, Rasmussen HM, Dallal GE, Dawson-Hughes B. Evaluation of an
inexpensive calcium absorption index in healthy older men and women. Clin Endocrinol (Oxf). 2010
Jan;72(1):22-5. Epub 2009 Mar 6. PMCID: In Process.
22. Ceglia L, Chiu GR, Harris SS, Araujo AB. Serum 25-hydroxyvitamin D concentration and physical
function in adult men. Clin Endocrinol (Oxf). 2011 Mar;74(3):370-6. PMCID: In Process.
23. Ceglia L, da Silva Morais M, Park LK, Morris E, Harris SS, Bischoff-Ferrari HA, Fielding RA, DawsonHughes B. Multi-step immunofluorescent analysis of vitamin D receptor loci and myosin heavy chain
isoforms in human skeletal muscle. J Mol Histol. 2010 Apr;41(2-3):137-42. Epub 2010 Jun 13. PMCID:
PMC2958104
24. Chalé-Rush A, Guralnik JM, Walkup MP, Miller ME, Rejeski WJ, Katula JA, King AC, Glynn NW, Manini
TM, Blair SN, Fielding RA. Relationship Between Physical Functioning and Physical Activity in the
Lifestyle Interventions and Independence for Elders Pilot. J Am Geriatr Soc. 2010 Oct;58(10):1918-24.
Epub 2010 Aug 24. PMCID: PMC2952066
25. Choong K, Basaria S. Emerging cardiometabolic complications of androgen deprivation therapy. Aging
Male. 2010 Mar;13(1):1-9. PMCID: In Process.
26. Clark DJ, Patten C, Reid KF, Carabello RJ, Phillips EM, Fielding RA. Impaired voluntary neuromuscular
activation limits muscle power in mobility-limited older adults. J Gerontol A Biol Sci Med Sci. 2010
May;65(5):495-502. Epub 2010 Feb 15. PMCID: PMC2854883.
27. Clark DJ, Patten C, Reid KF, Carabello RJ, Phillips EM, Fielding RA. Muscle performance and physical
function are associated with voluntary rate of neuromuscular activation in older adults. J Gerontol A Biol
Sci Med Sci. 2011 Jan;66(1):115-21. Epub 2010 Sep 9. PMCID: PMC3011959
28. Clough-Gorr KM, Stuck AE, Thwin SS, Silliman RA. Older breast cancer survivors: geriatric assessment
domains are associated with poor tolerance of treatment adverse effects and predict mortality over 7 years of
follow-up. J Clin Oncol. 2010 Jan 20;28(3):380-6. Epub 2009 Dec 14. PMCID: PMC2815700.
29. Collins JJ, Endy D, Hutchison CA 3rd, Roberts RJ. Editorial-synthetic biology. Nucleic Acids Res. 2010
May;38(8):2513. PMCID: PMC2860136.
30. Cohen SE, Lewis CA, Mooney RA, Kohanski MA, Collins JJ, Landick R, Walker GC. Roles for the
transcription elongation factor NusA in both DNA repair and damage tolerance pathways in Escherichia
coli. Proc Natl Acad Sci U S A. 2010 Aug 31;107(35):15517-22. Epub 2010 Aug 9. PMCID: PMC2932615
31. Conboy MJ, Cerletti M, Wagers AJ, Conboy IM. Immuno-analysis and FACS sorting of adult muscle
fiber-associated stem/precursor cells. Methods Mol Biol. 2010;621:165-73. PMCID: In Process.
32. Dawson-Hughes B, Castaneda-Sceppa C, Harris SS, Palermo NJ, Cloutier G, Ceglia L, Dallal GE. Impact
of supplementation with bicarbonate on lower-extremity muscle performance in older men and women.
Osteoporos Int. 2010 Jul;21(7):1171-9. Epub 2009 Sep 1. PMCID: PMC2888724
Boston OAIC 2010 Annual Directory
33. Edelstein D, Basaria S. Testosterone undecanoate in the treatment of male hypogonadism. Expert Opin
Pharmacother. 2010 Aug;11(12):2095-106. PMCID: In Process.
34. Eggermont LH, Gavett BE, Volkers KM, Blankevoort CG, Scherder EJ, Jefferson AL, Steinberg E, Nair A,
Green RC, Stern RA. Lower-extremity function in cognitively healthy aging, mild cognitive impairment,
and Alzheimer’s disease. Arch Phys Med Rehabil. 2010 Apr;91(4):584-8. PMCID: PMC2864645.
35. Farzanfar R, Locke SE, Heeren TC, Stevens A, Vachon L, Thi Nguyen MK, Friedman RH. Workplace
telecommunications technology to identify mental health disorders and facilitate self-help or professional
referrals. Am J Health Promot. 2011 Jan-Feb;25(3):207-16. PMCID: In Process.
36. Fernández-Balsells MM, Murad MH, Lane M, Lampropulos JF, Albuquerque F, Mullan RJ, Agrwal N,
Elamin MB, Gallegos-Orozco JF, Wang AT, Erwin PJ, Bhasin S, Montori VM. Clinical review 1: Adverse
effects of testosterone therapy in adult men: a systematic review and meta-analysis. J Clin Endocrinol
Metab. 2010 Jun;95(6):2560-75. PMCID: In Process.
37. Forsberg EC, Passegué E, Prohaska SS, Wagers AJ, Koeva M, Stuart JM, Weissman IL. Molecular
signatures of quiescent, mobilized and leukemia-initiating hematopoietic stem cells. PLoS One. 2010 Jan
20;5(1):e8785. PMCID: PMC2808351.
38. Gavett BE, Ozonoff A, Doktor V, Palmisano J, Nair AK, Green RC, Jefferson AL, Stern RA. Predicting
cognitive decline and conversion to Alzheimer’s disease in older adults using the NAB List Learning test. J
Int Neuropsychol Soc. 2010 Jul;16(4):651-60. Epub 2010 Apr 7. PMCID: PMC2922010.
39. Hall SA, Araujo AB, Kupelian V, Maserejian NN, Travison TG. Testosterone and breast cancer. J Sex
Med. 2010 Feb;7(2 Pt 2):1035-6; author reply 1036-7. Epub 2009 Oct 29. PMCID: In Process.
40. Hanchate AD, Clough-Gorr KM, Ash AS, Thwin SS, Silliman RA. Longitudinal Patterns in Survival,
Comorbidity, Healthcare Utilization and Quality of Care among Older Women Following Breast Cancer
Diagnosis. J Gen Intern Med. 2010 Oct;25(10):1045-50. Epub 2010 Jun 8. PMCID: PMCID: PMC2955471
41. Hawker G, Silman A, Aletaha D, Neogi T. 2010 RA Classification Criteria: An Indian (Asian) Perspective.
Arthritis Rheum. 2010 Nov 30. [Epub ahead of print]. PMCID: In Process.
42. Hettmer S, Wagers AJ. Muscling in: Uncovering the origins of rhabdomyosarcoma. Nat Med. 2010
Feb;16(2):171-3. PMCID: In Process.
43. Holt KG, Wagenaar RO, Saltzman E. A Dynamic Systems: constraints approach to rehabilitation. Rev
Bras Fisioter. 2010 Dec;14(6):446-63. PMCID: In Process.
44. Hsu FC, Rejeski WJ, Ip EH, Katula JA, Fielding R, Jette AM, Studenski SA, Blair SN, Miller ME.
Evaluation of the late life disability instrument in the Lifestyle Interventions and Independence for Elders
Pilot (LIFE-P) study. Health Qual Life Outcomes. 2010 Oct 6;8:115. PMCID: PMC2984553
45. Hunter DJ, Neogi T, Hochberg MC. Quality of osteoarthritis management and the need for reform in the
US. Arthritis Care Res (Hoboken). 2011 Jan;63(1):31-8. Epub 2010 Jun 25. PMCID: In Process.
46. Jefferson AL. Cardiac output as a potential risk factor for abnormal brain aging. J Alzheimers Dis.
2010;20(3):813-21. PMCID: PMC3041147.
47. Jefferson AL, Himali JJ, Beiser AS, Au R, Massaro JM, Seshadri S, Gona P, Salton CJ, Decarli C,
O’Donnell CJ, Benjamin EJ, Wolf PA, Manning WJ. Cardiac index is associated with brain aging: the
Framingham heart study. Circulation. 2010 Aug 17;122(7):690-7. Epub 2010 Aug 2. PMCID:
PMC2929763.
48. Jefferson AL, Lambe S, Chaisson C, Palmisano J, Horvath KJ, Karlawish J. Clinical Research Participation
among Aging Adults Enrolled in an Alzheimer's Disease Center Research Registry. J Alzheimers Dis. 2011
Jan 1;23(3):443-52. PMCID: In Process.
49. Jefferson AL, Lambe S, Cook E, Pimontel M, Palmisano J, Chaisson C. Factors associated with african
american and white elders' participation in a brain donation program. Alzheimer Dis Assoc Disord. 2011
Jan-Mar;25(1):11-6. PMCID: PMC3010335.
Boston OAIC 2010 Annual Directory
50. Jette AM. Invited commentary on the ICF and physical therapist practice. Phys Ther. 2010 Jul;90(7):10645; author reply 1066-7.
51. Jette AM, Latham N. Improving the evidence base for physical therapy disability interventions. Phys Ther.
2010 Mar;90(3):324-5.
52. Kapoor A, Labonte AJ, Winter MR, Segal JB, Silliman RA, Katz JN, Losina E, Berlowitz D. Risk of
venous thromboembolism after total hip and knee replacement in older adults with comorbidity and cooccurring comorbidities in the Nationwide Inpatient Sample (2003-2006). BMC Geriatr. 2010 Sep 17;10:63.
PMCID: PMC2949673
53. Keysor JJ, Jette AM, LaValley MP, Lewis CE, Torner JC, Nevitt MC, Felson DT; Multicenter
Osteoarthritis (MOST) group. Community environmental factors are associated with disability in older
adults with functional limitations: the MOST study. J Gerontol A Biol Sci Med Sci. 2010 Apr;65(4):393-9.
Epub 2009 Dec 8. PMCID: PMC2905834.
54. Khalil AS, Collins JJ. Synthetic biology: applications come of age. Nat Rev Genet. 2010 May;11(5):36779. PMCID: PMC2896386.
55. Kharlip J, Teytelboym O, Kleinberg L, Purtell M, Basaria S. Successful radiation therapy for cerebral
metastatic lesions from a pheochromocytoma. Endocr Pract. 2010 Mar-Apr;16(2):334-6. PMCID: In
Process.
56. Kohanski MA, DePristo MA, Collins JJ. Sublethal antibiotic treatment leads to multidrug resistance via
radical-induced mutagenesis. Mol Cell. 2010 Feb 12;37(3):311-20. PMCID: PMC2840266.
57. Kohanski MA, Dwyer DJ, Collins JJ. How antibiotics kill bacteria: from targets to networks. Nat Rev
Microbiol. 2010 Jun;8(6):423-35. Epub 2010 May 4. PMCID: PMC2896384.
58. Krasnoff JB, Basaria S, Pencina MJ, Jasuja GK, Vasan RS, Ulloor J, Zhang A, Coviello A, Kelly-Hayes M,
D’Agostino RB, Wolf PA, Bhasin S, Murabito JM. Free testosterone levels are associated with mobility
limitation and physical performance in community-dwelling men: the Framingham Offspring Study. J Clin
Endocrinol Metab. 2010 Jun;95(6):2790-9. Epub 2010 Apr 9. PMCID: PMC2902069
59. Kumar R, Atamna H, Zakharov MN, Bhasin S, Khan SH, Jasuja R. Role of the androgen receptor CAG
repeat polymorphism in prostate cancer, and spinal and bulbar muscular atrophy. Life Sci. 2011 Jan 31.
[Epub ahead of print]. PMCID: In Process.
60. Lambe S, Cantwell N, Islam F, Horvath K, Jefferson AL. Perceptions, Knowledge, Incentives, and Barriers
of Brain Donation Among African American Elders Enrolled in an Alzheimer’s Research Program.
Gerontologist. 2011 Feb;51(1):28-38. Epub 2010 Aug 2. PMCID: In Process.
61. Lakshman KM, Bhasin S, Araujo AB. Sex hormone-binding globulin as an independent predictor of
incident type 2 diabetes mellitus in men. J Gerontol A Biol Sci Med Sci. 2010 May;65(5):503-9. Epub 2010
Jan 27. PMCID: PMC2854882.
62. Lakshman KM, Kaplan B, Travison TG, Basaria S, Knapp PE, Singh AB, Lavalley MP, Mazer NA,
Bhasin S. The Effects of Injected Testosterone Dose and Age on the Conversion of Testosterone to
Estradiol and Dihydrotestosterone in Young and Older Men. J Clin Endocrinol Metab. 2010
Aug;95(8):3955-64. Epub 2010 Jun 9. PMCID: PMC2913038.
63. Lash TL, Cronin-Fenton D, Ahern TP, Rosenberg CL, Lunetta KL, Silliman RA, Garne JP, Sørensen HT,
Hellberg Y, Christensen M, Pedersen L, Hamilton-Dutoit S. CYP2D6 Inhibition and Breast Cancer
Recurrence in a Population-Based Study in Denmark. J Natl Cancer Inst. 2011 Feb 15. [Epub ahead of
print]. PMCID: In Process.
64. Lash TL, Cronin-Fenton D, Ahern TP, Rosenberg CL, Lunetta KL, Silliman RA, Hamilton-Dutoit S, Garne
JP, Ewertz M, Sørensen HT, Pedersen L. Breast cancer recurrence risk related to concurrent use of SSRI
antidepressants and tamoxifen. Acta Oncol. 2010 Apr;49(3):305-12. PMCID: PMC2892037.
65. Latham N, Liu CJ. Strength training in older adults: the benefits for osteoarthritis. Clin Geriatr Med. 2010
Aug;26(3):445-59. PMCID: In Process.
Boston OAIC 2010 Annual Directory
66. Lee HH, Molla MN, Cantor CR, Collins JJ. Bacterial charity work leads to population-wide resistance.
Nature. 2010 Sep 2;467(7311):82-5. PMCID: In Process.
67. Lessard SJ, Rivas DA, Stephenson EJ, Yaspelkis BB 3rd, Koch LG, Britton SL, Hawley JA. Exercise
training reverses impaired skeletal muscle metabolism induced by artificial selection for low aerobic
capacity. Am J Physiol Regul Integr Comp Physiol. 2011 Jan;300(1):R175-82. Epub 2010 Nov 3. PMCID:
PMC3023282.
68. Liu CK, Fielding RA. Exercise as an intervention for frailty. Clin Geriatr Med. 2011 Feb;27(1):101-10.
PMCID: PMC3005303
69. Liu CJ, Latham N. Adverse events reported in progressive resistance strength training trials in older adults:
2 sides of a coin. Arch Phys Med Rehabil. 2010 Sep;91(9):1471-3. PMCID: In Process.
70. Liu CJ, Latham N. Can progressive resistance strength training reduce physical disability in older adults? A
meta-analysis study. Disabil Rehabil. 2011;33(2):87-97. Epub 2010 May 17. PMCID: In Process.
71. Liu CJ, LaValley M, Latham NK. Do unblinded assessors bias muscle strength outcomes in randomized
controlled trials of progressive resistance strength training in older adults? Am J Phys Med Rehabil. 2011
Mar;90(3):190-6. PMCID: In Process.
72. Liu J, Sato C, Cerletti M, Wagers A. Notch signaling in the regulation of stem cell self-renewal and
differentiation. Curr Top Dev Biol. 2010;92:367-409. PMCID: In Process.
73. Loh YH, Hartung O, Li H, Guo C, Sahalie JM, Manos PD, Urbach A, Heffner GC, Grskovic M, Vigneault
F, Lensch MW, Park IH, Agarwal S, Church GM, Collins JJ, Irion S, Daley GQ. Reprogramming of T cells
from human peripheral blood. Cell Stem Cell. 2010 Jul 2;7(1):15-9. PMCID: PMC2913590.
74. Long KK, Montano M, Pavlath GK. Sca-1 is negatively regulated by TGF-β1 in myogenic cells. FASEB J.
2010 Dec 14. [Epub ahead of print]. PMCID: In Process.
75. Long KK, Pavlath GK, Montano M. Sca-1 influences the innate immune response during skeletal muscle
regeneration. Am J Physiol Cell Physiol. 2011 Feb;300(2):C287-94. Epub 2010 Dec 1. PMCID:
PMC3043632.
76. Luo Z, Zang M, Guo W. AMPK as a metabolic tumor suppressor: control of metabolism and cell growth.
Future Oncol. 2010 Mar;6(3):457-70. PMCID: PMC2854547.
77. Maggio M, Ceda GP, Lauretani F, Bandinelli S, Corsi AM, Giallauria F, Guralnik JM, Zuliani G, Cattabiani
C, Parrino S, Ablondi F, Dall'aglio E, Ceresini G, Basaria S, Ferrucci L. SHBG, Sex Hormones, and
Inflammatory Markers in Older Women. J Clin Endocrinol Metab. 2011 Jan 14. [Epub ahead of print].
PMCID: In Process.
78. Maggio M, Ceda GP, Lauretani F, Bandinelli S, Metter EJ, Guralnik JM, Basaria S, Cattabiani C, Luci M,
Dall'Aglio E, Vignali A, Volpi R, Valenti G, Ferrucci L. Gonadal status and physical performance in older
men. Aging Male. 2011 Mar;14(1):42-7. Epub 2010 Oct 12. PMCID: In Process.
79. Markovitz GH, Colthurst J, Storer TW, Cooper CB. Effective inspired oxygen concentration measured via
transtracheal and oral gas analysis. Respir Care. 2010 Apr;55(4):453-9. PMCID: In Process.
80. Mayack SR, Shadrach JL, Kim FS, Wagers AJ. Systemic signals regulate ageing and rejuvenation of blood
stem cell niches. Nature. 2010 Jan 28;463(7280):495-500. PMCID: In Process.
81. McDonough CM, Jette AM. The contribution of osteoarthritis to functional limitations and disability. Clin
Geriatr Med. 2010 Aug;26(3):387-99. PMCID: In Process.
82. McDonough CM, Tosteson TD, Tosteson AN, Jette AM, Grove MR, Weinstein JN. A Longitudinal
Comparison of 5 Preference-Weighted Health State Classification Systems in Persons with Intervertebral
Disk Herniation. Med Decis Making. 2010 Nov 22. [Epub ahead of print]. PMCID: In Process.
83. Meltzer M, Long K, Nie Y, Gupta M, Yang J, Montano M. The RNA editor gene ADAR1 is induced in
myoblasts by inflammatory ligands and buffers stress response. Clin Transl Sci. 2010 Jun;3(3):73-80.
PMCID: PMC2897727
Boston OAIC 2010 Annual Directory
84. Montano M, Long K. RNA surveillance-An emerging role for RNA regulatory networks in aging. Ageing
Res Rev. 2010 Feb 17. [Epub ahead of print]. PMCID: PMC2894286.
85. Morie M, Reid KF, Miciek R, Lajevardi N, Choong K, Krasnoff JB, Storer TW, Fielding RA, Bhasin S,
Lebrasseur NK. Habitual Physical Activity Levels Are Associated with Performance in Measures of
Physical Function and Mobility in Older Men. J Am Geriatr Soc. J Am Geriatr Soc. 2010 Sep;58(9):172733. PMCID: PMC2945416
86. Morley JE, Argiles JM, Evans WJ, Bhasin S, Cella D, Deutz NE, Doehner W, Fearon KC, Ferrucci L,
Hellerstein MK, Kalantar-Zadeh K, Lochs H, MacDonald N, Mulligan K, Muscaritoli M, Ponikowski P,
Posthauer ME, Rossi Fanelli F, Schambelan M, Schols AM, Schuster MW, Anker SD; Society for
Sarcopenia, Cachexia, and Wasting Disease. Nutritional recommendations for the management of
sarcopenia. J Am Med Dir Assoc. 2010 Jul;11(6):391-6. PMCID: In Process.
87. Murphy KF, Adams RM, Wang X, Balázsi G, Collins JJ. Tuning and controlling gene expression noise in
synthetic gene networks. Nucleic Acids Res. 2010 May;38(8):2712-26. Epub 2010 Mar 8. PMCID:
PMC2860118.
88. Napora JK, Short RG, Muller DC, Carlson OD, Odetunde JO, Xu X, Carducci M, Travison TG, Maggio M,
Egan JM, Basaria S. High-dose isoflavones do not improve metabolic and inflammatory parameters in
androgen-deprived men with prostate cancer. J Androl. 2011 Jan-Feb;32(1):40-8. Epub 2010 Aug 26.
PMCID: PMC3005077.
89. Neogi T. Clinical practice. Gout. N Engl J Med. 2011 Feb 3;364(5):443-52. PMCID: In Process.
90. Neogi T. IL-1 antagonism in acute gout: Is targeting a single cytokine the answer? Arthritis Rheum. 2010
Oct;62(10):2845-9. PMCID: PMC2952045.
91. Neogi T, Aletaha D, Silman AJ, Naden RL, Felson DT, Aggarwal R, Bingham CO 3rd, Birnbaum NS,
Burmester GR, Bykerk VP, Cohen MD, Combe B, Costenbader KH, Dougados M, Emery P, Ferraccioli G,
Hazes JM, Hobbs K, Huizinga TW, Kavanaugh A, Kay J, Khanna D, Kvien TK, Laing T, Liao K, Mease P,
Ménard HA, Moreland LW, Nair R, Pincus T, Ringold S, Smolen JS, Stanislawska-Biernat E, Symmons D,
Tak PP, Upchurch KS, Vencovský J, Wolfe F, Hawker G; American College of Rheumatology; European
League Against Rheumatism. The 2010 American College of Rheumatology/European League Against
Rheumatism classification criteria for rheumatoid arthritis: Phase 2 methodological report. Arthritis Rheum.
2010 Sep;62(9):2582-91. PMCID: In Process.
92. Neogi T, Nevitt M, Niu J, Sharma L, Roemer F, Guermazi A, Lewis CE, Torner J, Javaid K, Felson D.
Subchondral bone attrition may be a reflection of compartment-specific mechanical load: the MOST Study.
Ann Rheum Dis. 2010 May;69(5):841-4. Epub 2009 Sep 17. PMCID: PMC2891513.
93. Neogi T, Nevitt MC, Yang M, Curtis JR, Torner J, Felson DT. Consistency of Knee Pain: Correlates and
Association with Function. Osteoarthritis Cartilage. 2010 Oct;18(10):1250-5. Epub 2010 Aug 10. PMCID:
PMC2943545.
94. Neogi T, Terkeltaub R, Ellison RC, Hunt S, Zhang Y. Serum Urate Is Not Associated with Coronary Artery
Calcification: The NHLBI Family Heart Study. J Rheumatol. 2011 Jan;38(1):111-7. Epub 2010 Oct 1.
PMCID: In Process.
95 Neogi T, Zhang Y. Osteoarthritis prevention. Curr Opin Rheumatol. 2011 Mar;23(2):185-91. PMCID: In
Process.
96. Nevitt MC, Zhang Y, Javaid MK, Neogi T, Curtis JR, Niu J, McCulloch CE, Segal NA, Felson DT. High
systemic bone mineral density increases the risk of incident knee OA and joint space narrowing, but not
radiographic progression of existing knee OA: the MOST study. Ann Rheum Dis. 2010 Jan;69(1):163-8.
PMCID: PMC2935624.
97. Norweg A, Jette AM, Houlihan B, Ni P, Boninger ML. Patterns, predictors, and associated benefits of
driving a modified vehicle after spinal cord injury: findings from the national spinal cord injury model
systems. Arch Phys Med Rehabil. 2011 Mar;92(3):477-83. PMCID: In Process.
Boston OAIC 2010 Annual Directory
98. Norweg A, Jette AM, Ni P, Whiteson J, Kim M. Outcome measurement for COPD: reliability and validity
of the Dyspnea Management Questionnaire. Respir Med. 2011 Mar;105(3):442-53. Epub 2010 Sep 29.
PMCID: In Process.
99. O'Shaughnessy EC, Palani S, Collins JJ, Sarkar CA. Tunable signal processing in synthetic MAP kinase
cascades. Cell. 2011 Jan 7;144(1):119-31. PMCID: PMC3035479.
100. Pasiakos SM, McClung HL, McClung JP, Urso ML, Pikosky MA, Cloutier GJ, Fielding RA, Young AJ.
Molecular responses to moderate endurance exercise in skeletal muscle. Int J Sport Nutr Exerc Metab. 2010
Aug;20(4):282-90. PMCID: In Process.
101. Phillips EM, Katula J, Miller ME, Walkup MP, Brach JS, King AC, Rejeski WJ, Church T, Fielding RA.
Interruption of physical activity because of illness in the Lifestyle Interventions and Independence for
Elders Pilot trial. J Aging Phys Act. 2010 Jan;18(1):61-74. PMCID: In Process.
102. Polo JM, Liu S, Figueroa ME, Kulalert W, Eminli S, Tan KY, Apostolou E, Stadtfeld M, Li Y, Shioda T,
Natesan S, Wagers AJ, Melnick A, Evans T, Hochedlinger K. Cell type of origin influences the molecular
and functional properties of mouse induced pluripotent stem cells. Nat Biotechnol. 2010 Aug;28(8):848-55.
Epub 2010 Jul 19. PMCID: In Process.
103. Prakash A, Travison TG, Fogel MA, Hurwitz LM, Powell AJ, Printz BF, Puchalski MD, Shirali GS, Yoo
SJ, Geva T; Pediatric Heart Network Investigators. Relation of size of secondary ventricles to exercise
performance in children after fontan operation. Am J Cardiol. 2010 Dec 1;106(11):1652-6. PMCID: In
Process.
104. Rariy CM, Ratcliffe SJ, Weinstein R, Bhasin S, Blackman MR, Cauley JA, Robbins J, Zmuda JM, Harris
TB, Cappola AR. Higher Serum Free Testosterone Concentration in Older Women Is Associated with
Greater Bone Mineral Density, Lean Body Mass, and Total Fat Mass: the Cardiovascular Health Study. J
Clin Endocrinol Metab. 2011 Feb 2. [Epub ahead of print]. PMCID: In Process.
105. Rask-Madsen C, Li Q, Freund B, Feather D, Abramov R, Wu IH, Chen K, Yamamoto-Hiraoka J,
Goldenbogen J, Sotiropoulos KB, Clermont A, Geraldes P, Dall’Osso C, Wagers AJ, Huang PL, Rekhter
M, Scalia R, Kahn CR, King GL. Loss of insulin signaling in vascular endothelial cells accelerates
atherosclerosis in apolipoprotein E null mice. Cell Metab. 2010 May 5;11(5):379-89. PMCID:
PMC3020149.
106. Ringold S, Bittner R, Neogi T, Wallace CA, Singer NG. Performance of rheumatoid arthritis disease
activity measures and juvenile arthritis disease activity scores in polyarticular-course juvenile idiopathic
arthritis: Analysis of their ability to classify the American College of Rheumatology pediatric measures of
response and the preliminary criteria for flare and inactive disease. Arthritis Care Res (Hoboken). 2010
Aug;62(8):1095-102. PMCID: In Process.
107. Rivas DA, Fielding RA. Exercise as a countermeasure for sarcopenia. In: Sarcopenia – Age-Related
Muscle Wasting and Weakness: Mechanisms and Treatments. (ed., G.S. Lynch). Springer Dordrecht
Heidelberg; London, UK; New York, NY. ISBN 978-90-481-9712-5. Dec 2010.
108. Rivas DA, Fielding RA. Skeletal Muscle. In: Encyclopedia of Human Nutrition, 3rd edition. (eds. L.
Allen, A. Prentice). Elsevier, Oxford, UK. To be published 2012.
109. Rivas DA, Lessard SJ, Saito M, Friedhuber AM, Koch LG, Britton SL, Yaspelkis BB 3rd, Hawley JA.
Low intrinsic running capacity is associated with reduced skeletal muscle substrate oxidation and lower
mitochondrial content in white skeletal muscle. Am J Physiol Regul Integr Comp Physiol. 2011 Jan 26.
[Epub ahead of print]. PMCID: In Process.
110. Rivas DA., Morris EP, Fielding RA. Lipogenic regulators are elevated with age and chronic overload in
rat skeletal muscle. Acta Physiol. Accepted-In Press.
111. Roemer FW, Neogi T, Nevitt MC, Felson DT, Zhu Y, Zhang Y, Lynch JA, Javaid MK, Crema MD,
Torner J, Lewis CE, Guermazi A. Subchondral bone marrow lesions are highly associated with, and predict
subchondral bone attrition longitudinally: the MOST study. Osteoarthritis Cartilage. 2010 Jan;18(1):47-53.
Epub 2009 Sep 10. PMCID: PMC2818146.
Boston OAIC 2010 Annual Directory
112. Sattler F, Bhasin S, He J, Chou CP, Castaneda-Sceppa C, Yarasheski K, Binder E, Schroeder ET,
Kawakubo M, Zhang A, Roubenoff R, Azen S. Testosterone threshold levels and lean tissue mass targets
needed to enhance skeletal muscle strength and function: the HORMA trial. J Gerontol A Biol Sci Med Sci.
2011 Jan;66(1):122-9. Epub 2010 Nov 8. PMCID: PMC3032430
113. Schonberg MA, Marcantonio ER, Li D, Silliman RA, Ngo L, McCarthy EP. Breast cancer among the
oldest old: tumor characteristics, treatment choices, and survival. J Clin Oncol. 2010 Apr 20;28(12):203845. Epub 2010 Mar 22. PMCID: PMC2860406.
114. Schulz TJ, Huang TL, Tran TT, Zhang H, Townsend KL, Shadrach JL, Cerletti M, McDougall LE,
Giorgadze N, Tchkonia T, Schrier D, Falb D, Kirkland JL, Wagers AJ, Tseng YH. Identification of
inducible brown adipocyte progenitors residing in skeletal muscle and white fat. Proc Natl Acad Sci U S A.
2011 Jan 4;108(1):143-8. Epub 2010 Dec 20. PMCID: PMC3017184.
115. Sebastiani P, Solovieff N, Puca A, Hartley SW, Melista E, Andersen S, Dworkis DA, Wilk JB, Myers RH,
Steinberg MH, Montano M, Baldwin CT, Perls TT. Genetic Signatures of Exceptional Longevity in
Humans. Science. 2010 Jul 21. [Epub ahead of print]. PMCID: In Process.
116. Serra C, Bhasin S, Tangherlini F, Barton ER, Ganno M, Zhang A, Shansky J, Vandenburgh HH,
Travison TG, Jasuja R, Morris C. The role of GH and IGF-I in mediating anabolic effects of testosterone
on androgen-responsive muscle. Endocrinology. 2011 Jan;152(1):193-206. Epub 2010 Nov 17. PMCID:
PMC3033058.
117. Slavin MD, Kisala PA, Jette AM, Tulsky DS. Developing a contemporary functional outcome measure for
spinal cord injury research. Spinal Cord. 2010 Mar;48(3):262-7. Epub 2009 Oct 20. PMCID: In Process.
118. Song G, Nguyen DT, Pietramaggiori G, Scherer S, Chen B, Zhan Q, Ogawa R, Yannas IV, Wagers AJ,
Orgill DP, Murphy GF. Use of the parabiotic model in studies of cutaneous wound healing to define the
participation of circulating cells. Wound Repair Regen. 2010 Jul-Aug;18(4):426-32. Epub 2010 Jun 8.
PMCID: PMC2935287.
119. Smith K, Weissberg E, Travison TG. Alternative Methods of Refraction: A Comparison of Three
Techniques. Optom Vis Sci. 2010 Jan 14. [Epub ahead of print]. PMCID: In Process.
120. Takahashi K, Tickle-Degnen L, Coster WJ, Latham NK. Expressive behavior in Parkinson’s disease as a
function of interview context. Am J Occup Ther. 2010 May-Jun;64(3):484-95. PMCID: PMC2922955.
121. Tao R, Gong J, Luo X, Zang M, Guo W, Wen R, Luo Z. AMPK exerts dual regulatory effects on the PI3K
pathway. J Mol Signal. 2010 Feb 18;5(1):1. PMCID: PMC2848036.
122. Taylor PL, Barker RA, Blume KG, Cattaneo E, Colman A, Deng H, Edgar H, Fox IJ, Gerstle C, Goldstein
LS, High KA, Lyall A, Parkman R, Pitossi FJ, Prentice ED, Rooke HM, Sipp DA, Srivastava A, Stayn S,
Steinberg GK, Wagers AJ, Weissman IL. Patients beware: commercialized stem cell treatments on the web.
Cell Stem Cell. 2010 Jul 2;7(1):43-9. Epub 2010 Jun 17. PMCID: In Process.
123. Tickle-Degnen L, Ellis T, Saint-Hilaire MH, Thomas CA, Wagenaar RC. Self-management rehabilitation
and health-related quality of life in Parkinson’s disease: a randomized controlled trial. Mov Disord. 2010
Jan 30;25(2):194-204. PMCID: PMC2831132.
124. Travison TG, Chiu GR, McKinlay JB, Araujo AB. Accounting for racial/ethnic variation in bone mineral
content and density: the competing influences of socioeconomic factors, body composition, health and
lifestyle, and circulating androgens and estrogens. Osteoporos Int. 2011 Jan 6. [Epub ahead of print].
PMCID: In Process.
125. Travison TG, Shackelton R, Araujo AB, Morley JE, Williams RE, Clark RV, McKinlay JB. Frailty,
serum androgens, and the CAG repeat polymorphism: results from the Massachusetts Male Aging Study. J
Clin Endocrinol Metab. 2010 Jun;95(6):2746-54. Epub 2010 Apr 21.PMCID: PMC2902073.
126. Trudeau K, Molina AJ, Guo W, Roy S. High Glucose Disrupts Mitochondrial Morphology in Retinal
Endothelial Cells. Implications for Diabetic Retinopathy. Am J Pathol. 2010 Jul;177(1):447-55. Epub 2010
Jun 3. PMCID: PMC2893686.
127. Wagenaar RC. Invited commentary. Phys Ther. 2010 Jul;90(7):997-9; author reply 999-1000.
Boston OAIC 2010 Annual Directory
128. Wagers A. Delivering on a promise. Interviewed by Kristie Nybo. Biotechniques. 2010 Aug;49(2):545.
129. Wang C. Tai chi and rheumatic diseases. Rheum Dis Clin North Am. 2011 Feb;37(1):19-32. Epub 2010
Dec 4. PMCID: In Process.
130. Wang C, Bannuru R, Ramel J, Kupelnick B, Scott T, Schmid CH. Tai Chi on psychological well-being:
systematic review and meta-analysis. BMC Complement Altern Med. 2010 May 21;10:23. PMCID:
PMC2893078.
131. Wang C, Schmid CH, Rones R, Kalish R, Yinh J, Goldenberg DL, Lee Y, McAlindon T. A randomized
trial of tai chi for fibromyalgia. N Engl J Med 2010 Aug 19;363(8):743-54. PMCID: PMC3023168.
132. Warren L, Manos PD, Ahfeldt T, Loh YH, Li H, Lau F, Ebina W, Mandal PK, Smith ZD, Meissner A,
Daley GQ, Brack AS, Collins JJ, Cowan C, Schlaeger TM, Rossi DJ. Highly efficient reprogramming to
pluripotency and directed differentiation of human cells with synthetic modified mRNA. Cell Stem Cell.
2010 Nov 5;7(5):618-30. Epub 2010 Sep 30. PMCID: In Process.
133. White DK, Jette AM, Felson DT, Lavalley MP, Lewis CE, Torner JC, Nevitt MC, Keysor JJ. Are features
of the neighborhood environment associated with disability in older adults? Disabil Rehabil.
2010;32(8):639-45. PMCID: PMC2908013.
134. White DK, Keysor JJ, Lavalley MP, Lewis CE, Torner JC, Nevitt MC, Felson DT. Clinically important
improvement in function is common in people with or at high risk of knee OA: the MOST study. J
Rheumatol. 2010 Jun;37(6):1244-51. Epub 2010 Apr 15. PMCID: PMC2913686.
135. White DK, Zhang Y, Felson DT, Niu J, Keysor JJ, Nevitt MC, Lewis CE, Torner JC, Neogi T. The
independent effect of pain in one versus two knees on the presence of low physical function in a multicenter
knee osteoarthritis study. Arthritis Care Res (Hoboken). 2010 Jul;62(7):938-43. PMCID: PMC2902715.
136. White DK, Zhang Y, Niu J, Keysor JJ, Nevitt MC, Lewis CE, Torner JC, Neogi T. Do worsening knee
radiographs mean greater chance of severe functional limitation? The multicenter osteoarthritis study.
Arthritis Care Res (Hoboken). 2010 Oct;62(10):1433-9. PMCID: PMC2939286.
137. Woo M, Isganaitis E, Cerletti M, Fitzpatrick C, Wagers A, Jimenez-Chillaron J, Patti ME. Early Life
Nutrition Modulates Muscle Stem Cell Number: Implications for Muscle Mass and Repair. Stem Cells Dev.
2011 Jan 19. [Epub ahead of print]. PMCID: In Process.
138. Yaspelkis III BB, Kvasha IA, Lessard SJ, Rivas DA, Hawley JA. Aerobic training reverses high-fat dietinduced pro-inflammatory signalling in rat skeletal muscle. Eur J Appl Physiol. 2010 Nov;110(4):779-88.
Epub 2010 Jul 2. PMCID: In Process.
139. Young DE, Wagenaar RC, Lin CC, Chou YH, Davidsdottir S, Saltzman E, Cronin-Golomb A.
Visuospatial perception and navigation in Parkinson's disease. Vision Res. 2010 Nov 23;50(23):2495-504.
Epub 2010 Sep 15. PMCID: PMC3008343.
140. Young AP, Wagers AJ. Pax3 induces differentiation of juvenile skeletal muscle stem cells without
transcriptional upregulation of canonical myogenic regulatory factors. J Cell Sci. 2010 Aug 1;123(Pt
15):2632-9. Epub 2010 Jul 6. PMCID: PMC2908050.
141. Zhang Y, Niu J, Felson DT, Choi HK, Nevitt M, Neogi T. Methodological challenges in studying risk
factors for progression of knee osteoarthritis. Arthritis Care Res (Hoboken). 2010 Nov;62(11):1527-32.
Epub 2010 Jul 8. PMCID: PMC2959151.
High impact publications in high impact journals
• Basaria S, Coviello AD, Travison TG, Storer TW, Farwell WR, Jette AM, Eder R, Tennstedt S,
Ulloor J, Zhang A, Choong K, Lakshman KM, Mazer NA, Miciek R, Krasnoff J, Elmi A, Knapp PE,
Brooks B, Appleman E, Aggarwal S, Bhasin G, Hede-Brierley L, Bhatia A, Collins L, LeBrasseur N,
Fiore LD, Bhasin S. N Engl J Med. 2010 Jul 8;363(2):109-22.
• Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, Montori VM; Task
Force, Endocrine Society. Testosterone therapy in men with androgen deficiency syndromes: an
Boston OAIC 2010 Annual Directory
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Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010 Jun;95(6):2536-59.
PMCID: In Process.
Cohen SE, Lewis CA, Mooney RA, Kohanski MA, Collins JJ, Landick R, Walker GC. Proc Natl Acad
Sci U S A 2010 Aug 9. [Epub ahead of print]
Hettmer S, Wagers AJ. Nat Med 2010;16:171-3.
Khalil AS, Collins JJ. Nat Rev Genet 2010;11:367-79.
Kohanski MA, DePristo MA, Collins JJ. Mol Cell 2010;37:311-20.
Lee HH, Molla MN, Cantor CR, Collins JJ. Nature 2010;467:82-5.
Mayack SR, Shadrach JL, Kim FS, Wagers AJ. Nature 2010;463:495-500.
Schulz TJ, Huang TL, Tran TT, Zhang H, Townsend KL, Shadrach JL, Cerletti M, McDougall LE,
Giorgadze N, Tchkonia T, Schrier D, Falb D, Kirkland JL, Wagers AJ, Tseng YH. Proc Natl Acad Sci
U S A. 2011;108:143-8.
Sebastiani P, Solovieff N, Puca A, Hartley SW, Melista E, Andersen S, Dworkis DA, Wilk JB, Myers
RH, Steinberg MH, Montano M, Baldwin CT, Perls TT. Science 2010 Jul 21
Wang C, Schmid CH, Rones R, Kalish R, Yinh J, Goldenberg DL, Lee Y, McAlindon T. N Engl J Med
2010;363:743-54.
Neogi T, Aletaha D, Silman AJ, Naden RL, Felson DT, Aggarwal R, Bingham CO 3rd, Birnbaum NS,
Burmester GR, Bykerk VP, Cohen MD, Combe B, Costenbader KH, Dougados M, Emery P, Ferraccioli
G, Hazes JM, Hobbs K, Huizinga TW, Kavanaugh A, Kay J, Khanna D, Kvien TK, Laing T, Liao K,
Mease P, Ménard HA, Moreland LW, Nair R, Pincus T, Ringold S, Smolen JS, Stanislawska-Biernat E,
Symmons D, Tak PP, Upchurch KS, Vencovský J, Wolfe F, Hawker G; American College of
Rheumatology; European League Against Rheumatism. The 2010 American College of
Rheumatology/European League Against Rheumatism classification criteria for rheumatoid arthritis:
Phase 2 methodological report. Arthritis Rheum. 2010 Sep;62(9):2582-91.
BOSTON CLAUDE D. PEPPER OLDER AMERICANS INDEPENDENCE CENTER
FOR FUNCTION PROMOTING ANABOLIC THERAPIES
BOSTON MEDICAL CENTER • BOSTON UNIVERSITY • TUFTS UNIVERSITY • JOSLIN DIABETES CENTER
The Boston Claude D. Pepper Older Americans Independence Center
for Function Promoting Anabolic Therapies
2010 OAIC Annual Directory
Recognition and Awards
Shalender Bhasin, MD was appointed Chair of American Board of Internal Medicine, Endocrinology and
Metabolism subspecialty board. Dr. Bhasin was also appointed to Council of the Endocrine Society.
Camellia Banerjee and Monty Montano, PhD received first place at the Boston University 2010 Evans Day
for their poster on “Biomarkers for aging and anabolic response.”
James Collins, PhD was named a Howard Hughes Medical Institute Investigator. Additionally, Dr. Collins
received Boston University’s DISTINGUISHED PROFESSOR Award.
Alan M. Jette, PhD was awarded the 2010 Distinguished Public Service Award from the American Academy
of Physical Medicine and Rehabilitation (AAPM&R)
Christine Liu, MD, a third year Geriatric Medicine fellow, successfully defended her thesis entitled: “The
impact of sarcopenia on the response to a physical activity intervention in older adults” on Friday May 20,
2011 in partial fulfillment of requirements for her Master's degree in Epidemiology.
Tuhina Neogi, MD, Ph.D. was named Co-Director of Evidence Based Medicine and Critical Thinking as part
of the Internal Medicine Residency Training Program at the Boston University School of Medicine. Dr. Neogi
also became an elected member of the Delta Omega Honor Society for her academic record.
Kieran Reid, MS, MPH received the 2011 NOMA Award for Excellence in Multicultural Aging from the
American Society on Aging (ASA) for The Fit-4-Life Program.
Rebecca A. Silliman, MD, Ph.D. received the Department of Medicine Mentoring Award in recognition of her
excellence in research mentoring from Boston University School of Medicine.
Thomas W. Storer, PhD was the keynote speaker at Harvard Medical School’s 24th Annual International
Conference on Practical Approaches to the Treatment of Obesity. “Prevention vs. Rehab in Cardiovascular
Exercise”
Thomas Travison, PhD was named an International Visiting Research Fellow at the University of Sydney’s
ANZAC Institute.
Boston OAIC 2010 Annual Directory
Amy Wagers, PhD, received the Early Career Award from Howard Hughes Medical Institute.
Daniel K. White received a ‘Rheumatology Investigator Award’ from the Research and Education Foundation
of the American College of Rheumatology.
BOSTON CLAUDE D. PEPPER OLDER AMERICANS INDEPENDENCE CENTER
FOR FUNCTION PROMOTING ANABOLIC THERAPIES
BOSTON MEDICAL CENTER • BOSTON UNIVERSITY • TUFTS UNIVERSITY • JOSLIN DIABETES CENTER
The Boston Claude D. Pepper Older Americans Independence Center
for Function Promoting Anabolic Therapies
2010 OAIC Annual Directory
Minority Research
Donato Rivas, Ph.D has participated in research and career development activities associated with the Boston
OAIC under the mentorship of Dr. Roger Fielding. His research activities include conducting mentored research
in the anabolic pathways that mediate the effects of exercise training on the skeletal muscle in the laboratory of
Dr. Roger Fielding (Boston OAIC Associate Director). He has and will continue to take selected courses on
topics related to aging and geriatrics, and molecular genetics, and participate in the career development
opportunities available to trainees through the Boston OAIC.
Dr. Rivas was awarded supplemental funds for two years through the Boston OAIC under the Research
Supplements to Promote Diversity in Health-Related Research Program in September 2009. To date, Dr. Rivas
has taken part in the NIA Grants Technical Assistance Workshop where he took part in discussions and lectures
on how best to write and review grants during two days of intensive training. Additionally, he has taken on a
leadership role as a representative of the Biological Section of the Emerging Scholar and Professional
Organization of the Gerontological Society of America. In this role he has been tasked with organizing the
Biological Section’s ESPO seminar during GSA’s Annual Meeting. Dr. Rivas attended the ISOTOPE
TRACERS IN METABOLIC RESEARCH course in Little Rock, AR on April 12-16, 2010 where he learned
how to use isotope tracers for use in human and animal studies. He has also taken on the lead role for a human
study and has been able to interact with older human subjects resulting in developing his ability to make
assessments on people in this age category.
Mara Banks, MD, PhD is a student at Boston University who is working under the mentorship of Dr. Michael
Holick to determine the relationship of vitamin D and physical function in older individuals with diabetes
mellitus. She is supported jointly by the T32 training grant and the Boston OAIC.
Angela Chale-Rush, PhD, RD is a Human Nutrition and Metabolism Fellow in the Nutrition, Exercise
Physiology and Sarcopenia Laboratory at the Jean Mayer USDA Human Nutrition Research Center on Aging at
Tufts University. She is involved in studies investigating the effect of protein supplementation and resistance
training on skeletal muscle parameters, physical function, glucose metabolism and vascular dynamics in
mobility limited older adults as well as molecular mechanisms of skeletal muscle anabolism. The recipient of a
Ross Aging Initiative grant, Dr. Chale-Rush is also examining the interrelationship between chemosensitivity
and physical activity in older adults.
Duke University Medical Center
Claude D. Pepper Older Americans Independence Center
Harvey J. Cohen, M.D.
Principal Investigator
Miriam C. Morey, Ph.D.
Co-Director
Phone
919-660-7500
Fax
919-684-8569
Electronic Mail
[email protected]
919-286-0411 x6776
919-286-6823
[email protected]
Mailing Address: Box 3003, D.U.M.C., Durham, North Carolina 27710
SECTION I.
DESCRIPTION OF CENTER
The overall theme of our center is “to understand and modify multiple pathways of functional
decline.” The Duke Claude D. Pepper Older Americans Independence Center (Pepper Center) is
based in the Duke Center for the Study of Aging and Human Development, an all-university
program with strong multidisciplinary affiliated programs such as the Durham VA GRECC, the
RAND/Hartford Interdisciplinary Geriatric Research Center, the Duke Institute for Genomic
Sciences and Policy, the Duke Clinical Research Institute, the Duke Center for Living,
Trajectories of Aging and Care Center, and the Stedman Nutrition and Metabolism Center. This
rich milieu includes 126 faculty as Senior Fellows of the Aging Center and over 21 million
dollars of research germane to our center goals.
Over the past seventeen years, the Duke Pepper Center has been at the forefront of geriatric
research and training focused on the development of interventions to improve the functional
status of older adults and the support of research that identifies risk factors predictive of
functional decline. The Duke Pepper Center originally began its funding as a Geriatric Research
and Training Center (GRTC) in 1991. The GRTC was originally funded with three research
cores and support for junior faculty and pilot projects, which reflects the organization of the
current OAIC structure. One year later, Duke was awarded a Pepper Center and, at the direction
of the National Institute on Aging, the two programs were combined into one. Initial Pepper
Center support focused on the development of promising interventions to promote the
independence of older Americans and faculty development. Since then, the Duke OAIC has
produced an impressive portfolio of relevant research and innovations in faculty development.
The specific goals of the Duke Pepper Center are:
1) Support and enhance research related to our Center theme of exploring modifiable pathways
to functional decline;
2) Train investigators in the methodologies needed for competence in mechanistic, translational,
and outcomes research aimed at exploring modifiable pathways to functional decline;
3) Identify and nurture promising new and transitioning investigators who have an interest in
research aimed at modifying functional decline in later life.
SECTION II.
RESEARCH, RESOURCES, AND ACTIVITIES
The Duke Pepper Center supports two research cores which have evolved from prior support:
(1) an Analysis Core and (2) a Biological Studies Core. Six externally funded NIH/VA grants,
with study aims and study populations that integrate into our thematic focus, receives support
from these cores; with new specific research aims relevant to our Center. The Research Career
Development Core and the Pilot/Exploratory Studies Core facilitates career development with
established post-doctoral Research and Geriatric Training Programs. During the first year, three
pilot projects, two development projects from each research core, and three junior faculty were
supported. Subsequent support for career development and pilot projects are selected on a
competitive basis using criteria clearly defined in the Pepper Center guidelines. The Leadership/
Administrative Core direct and coordinates activities to ensure continued integration of center
activities.
PUBLIC IMPACT: The public impact will be a significant advancement in the basic
understanding of the multiple factors that contribute to functional decline, and the enhancement
of interventions directed at improving the overall quality of life of older adults.
A. CORES
1. RESEARCH CORE 1: ANALYSIS CORE
Carl F. Pieper, D.P.H., Core Leader
Tel: (919) 660-7525 FAX: (919) 684-8569 E-mail: [email protected]
The Analysis Core provides analytic and technical support to the funded grants, pilots, projects
and junior faculty in the Pepper. The Core provides mentoring, consultation and advice to
approved projects and people and pursue two general goals: to collaborate with the projects and
researchers of the Pepper Center with appropriate and innovative analytic and data management
technologies, and to advance statistical science in the study of function and functional decline.
The Analysis Core work closely with the Biological Studies Core (RC2) to direct and perform
the requisite analyses from the data derived from that Core. Members of this core sit on the
Internal Operating Committee and are involved in selecting and assisting in the design of future
projects, pilots, and junior faculty. To accomplish these goals, the Analysis Core has four
specific aims:
1) Provide R01s, pilot projects, and junior faculty investigators with analytic and technical
support by which to conduct research and to address hypotheses related to functional decline and
the aging process;
2) Provides a panel of experts for consultation in measurement, functional assessment, and
analysis to the Duke Pepper Center researchers;
3) Further analytic science in the study of function.
4) Build a “Data base of Databases” resource available for secondary analyses to both Pepper
researchers within Duke, and other Pepper Centers;
2. RESEARCH CORE 2: BIOLOGICAL STUDIES CORE
Virginia B. Kraus, M.D., Ph.D., Core Leader
Tel: (919) 681-6652 FAX: (919) 684-8907 E-mail: [email protected]
The Biological Studies Core provides a comprehensive biomarkers phenotyping technology to
characterize the biochemical, metabolic and genetic bases for the functional decline associated
with aging and degenerative processes associated with aging. It also provides a central resource
for biomarkers and a means of testing common hypotheses across the various projects related to
aging and functional decline. The overall approach is one of a 'Collaboratory' in which multiple
excellent clinical research studies contribute subsets of samples for biochemical, metabolic and
genetic biomarker analyses. This “Collaboratory” approach is designed to bring us closer to a
molecular understanding of aging and functional decline. This aids in the early identification of
risk profiles and the development of targeted interventions to forestall and/or reverse detrimental
trends in function. Collaborating studies contributing samples for analysis includes 5 NIH
funded RO1s, a VA Rehabilitation Research and Development Merit Review Award and 3
Junior Faculty projects (8 of 9 of these studies are conducted in humans). The technology made
available through the Biological Studies Core provides the ability to answer questions that were
previously unavailable to each of the major projects supported. The first phase of research
relates to discovery of biomarkers indicative of age and function. The latter phase of the grant
will be devoted to biomarker validation using samples from an alternative subset of individuals
from subsequent phases of the collaborating studies and new collaborating studies to be
identified. In addition, this Core undertakes two Developmental Projects relating to development
and assessment of potential new biomarkers of biological aging, namely quantification of
racemized and isomerized aspartate, and profiling of sphingolipid by mass spectrometry. This
Core serves as a resource for the training of investigators on principles and methods of
biomarker analyses. To accomplish these goals the Biological Studies Core has six specific
aims:
1) Perform metabolic and biochemical profiling on individuals of varying ages, with a variety of
morbidities and of varying functional status;
2) Utilize biochemical markers associated with functional status, joint tissue metabolism, and
inflammation, as quantitative traits in Amish families (External Project 1) and a large extended
family (Pilot Project 2);
3) Evaluate candidate genes associated with aging and functional decline;
4) Evaluate use of the combination of metabolic, biochemical and genetic markers and traditional
risk factors to predict functional decline with aging;
5) Develop the capacity to measure new age-related markers;
6) Serve as a resource for research-oriented training of health professionals on principles and
methods of metabolic, biochemical and genetic marker analyses.
3. RESEARCH CAREER DEVELOPMENT CORE
Kenneth W. Lyles, M.D., Core Leader
Tel: (919) 660-7520 FAX: (919) 684-8569
E-mail: [email protected]
The goal of the Research Career Development Core (RCD Core) is to recruit, train, mentor, and
develop future research leaders with skills in translational research and clinical investigation
directed at exploring approaches to understand and modify multiple pathways of functional
decline. Promising scientists are recruited to develop and/or expand their investigative skills
with an emphasis on translating basic research findings into clinical studies or, taking clinical
research findings and posing new basic research questions. RCD Core awardees take courses
tailored to their specific career needs, receive mentoring from senior faculty members, and
receive leadership training to prepare them for key positions in geriatrics and gerontology. Our
mentoring plan is designed to motivate clinical investigators to explore basic research principles
and basic scientists to interface with clinical researchers. The RCD Core ensures its awardees to
take advantage of other Pepper Center research cores and other experienced investigators at
Duke University Medical Center. RCD Core awardees participate in seminars and conferences
where interdisciplinary investigators discuss their work. In these settings, ideas for translational
collaborations are raised and discussed, resulting in new projects and studies. Close
collaborative links with other programs and centers at Duke University is available to RCD Core
awardees, e.g., Duke Clinical Research Institute; Health Services Research Program, VAMC;
Established Population for Epidemiologic Studies of the Elderly; RAND/Hartford
Interdisciplinary Geriatric Health Care Center; the Institute for Genome Sciences and Policy, and
the Duke University Medical Center Mentored Clinical Research Scholar Program (MSRSP).
The RCD Core helps awardees develop interdisciplinary projects and use these programs, Center
and Institutes to foster translational research studies. A listing of past and current awardees is
listed in section III.
4. PILOT/ EXPLORATORY STUDIES CORE
Kenneth E. Schmader, M.D., Core Leader
Tel: (919) 286-6932 FAX: (919)286-6823 E-mail: [email protected]
The overall objective of the Pilot/Exploratory Studies Core (P/E Studies Core) is to conduct pilot
studies to acquire information needed to select or design future crucial studies in the Duke
Pepper’s area of research focus. The P/E Studies Core orchestrates several key activities to
generate productive pilot studies. These activities include formal methods to solicit and select
pilot studies via the Duke Pepper Pilot Grants Program and Pilot Studies Workshop Series and a
multifaceted plan for monitoring study progress and larger proposal development. There are six
specific aims associated with this core:
1) Generate ideas and enhance the intellectual environment for the development of
pilot/exploratory studies of approaches to understand and modify multiple pathways of
functional decline;
2) Solicit, select and provide research funding for the highest quality pilot studies and
investigators;
3) Facilitate successful completion of the pilot studies and their development into externally
funded, larger grants;
4) Attract, support, and further develop promising junior investigators to aging research in
coordination with activities of the Research Career Development Core;
5) Grow areas of research foci for future Duke Pepper OIAC applications;
6) Educate developing investigators about the logistics and science of pilot studies via pilot
studies workshops.
5. LEADERSHIP/ ADMINISTRATIVE CORE
Harvey J. Cohen, M.D., Core Leader
and Principle Investigator
Tel: (919) 660-7500
FAX: (919) 684-8569 E-mail: [email protected]
Miriam C. Morey, Ph.D., Co-Core Leader and Co-Center Director
Tel: (919) 286-0411-1-6776 FAX: (919) 286-6823 E-mail: [email protected]
Jamazina Smith, Staff Assistant
Tel: (919) 660-7502
FAX: (919) 684-8569
E-mail: [email protected]
The Leadership/Administrative Core (L/AC) has responsibility for the overall direction and
operation of the Duke Pepper Center. The L/AC will provide the leadership necessary to harness
and direct the creative energy of this complex research activity. The Core will have input from,
and interaction with, key members of other units of the Medical Center, the University, and the
Durham VA and relies on two panels, Independent Review Panel and External Advisory
Committee for expertise and direction in selection of future projects, pilots and junior faculty
awardees. The Pepper Center Operating Committee is the primary mechanism for problem
solving and planning. Monthly meetings composed of core leaders, key program advisors and
administrative staff which are Co-chaired by Drs. Cohen and Morey to review the status of all
center related activities and strategies to move forward with the proposed work. The specific
goals of the L/AC are:
(1) Assure overall coordination, integration, and administration of the Duke Pepper Center;
(2) Assure integration with other affiliated programs;
(3) Assure efficient and appropriate use of core facilities by investigators and programs;
(4) Plan and develop funding strategies for cores and support of projects related to cores;
(5) Plan and coordinate future core activities and integrate Pepper Center activities with new
programs established at Duke Medical Center.
THE PEPPER CENTER SCHOLARS
Since its inception, the Duke Pepper Center has produced an impressive portfolio of relevant
research and innovations in faculty development. One of its many accomplishments is support
and mentoring of numerous promising investigators whose careers focus on relevant aging
related research at Duke. In 2009 in recognition of the contributions of these young
investigators, the Duke Pepper Center established a Duke Pepper Scholars Program.
2009 Pepper Scholars:
James T. Cavanaugh PT, Ph.D., Assistant Research Professor
Medicine – Division of Geriatrics, DUMC
Kim Huffman, M.D., Medical Instructor,
Department of Rheumatology and Immunology, DUMC
Deborah M. Muoio, Ph.D., Assistant Professor
Medicine – Endocrinology & Metabolomics, DUMC
Jama L. Purser, PT, Ph.D., Assistant Research Professor
Medicine – Division of Geriatrics, DUMC
Svati H. Shah, M.D., M.H.S. Assistant Professor
Medicine, (Epidemiology) M.H.S. (Medical Genomics), DUMC
Heather E. Whitson, M.D. – Assistant Professor
Medicine - Division of Geriatrics, DUMC
Beverly Brummett, M.D. – Associate Professor
Medicine – Medical Psychology
2010 Pepper Center Scholars:
Jennifer Dungan, RN, PhD - Research Associate
School of Nursing
Timothy Koves, PhD - Assistant Professor
Medicine – Geriatrics
Thomas Povsic, MD – Assistant Professor
Medicine - Cardiology
Amy Pastva, PhD – Assistant Research Professor
Department of Community and Family Medicine
William Michael Foster, PhD - Research Professor
Medicine - Pulmonary and Critical Care Medicine
Matthew Peterson, PhD – Assistant Professor
Medicine - Geriatrics
Lee Jones, PhD – Associate Professor
Radiation Oncology
Kelli Allen, PhD – Associate Professor
General Internal Medicine
Jessica Chia, MD – Medical Instructor
Medicine – Pulmonary, Allergy and Critical Care Medicine
Jason Allen, PhD – Assistant Professor
Medicine - Cardiology
Gregory Sempowski, PhD – Associate Professor
Medicine – Duke Human Vaccine Institute
David Madden, PhD – Professor
Medicine – Psychiatry and Behaviorial Sciences
Beverly Brummett, M.D. – Associate Professor
Medicine – Medical Psychology
Helen Lum, MD – Medical Instructor/Duke Post Doctoral Training Program
Medicine - Geriatrics
B. CENTER RESEARCH PROJECTS
1. ANALYSIS CORE DEVELOPMENT PROJECT 1
ADVANCING ANALYTIC METHODS IN THE STUDY OF FUNCTION
Carl F. Pieper, D.P.H.- Project Leader
Tel: (919) 660-7525 FAX: (919) 684-8569 E-mail: [email protected]
Funding Years: July 01, 2007 – June 30, 2009
The overall aims of this development project are to advance the analytic and statistical science of
change and typologies of function and to apply these methods to the data sets and analytic issues
in the Duke Pepper Center. The results of this project are intended to have utility in (1) analysis
of aims of the parent grant, and (2) advancement of statistical/ methodogical science. In the first
year, we have developed methodological techniques which can simultaneously analyze multiple
trajectories. In year two, in addition to developing models for the analysis of multiple
trajectories, we proposed to assess if the data collected in the Pepper Center projects were
amenable to Latent Trait/Latent Class Analysis. We will employ these methods to the metabolite
data to assess if classes of subjects can be discerned. Typically, outcomes are analyzed
‘univariately’ (one outcome at a time). Analyzing data multivariately has several advantages –
(1) power is increased, (2) the correlation between predictors of trajectories is easily assessed,
and (3) temporal ordering can be established between changes. To accomplish this, we have
utilized and extended Structural Equation Models (SEM) to incorporate multiple outcomes and
to develop a factor structure on the trajectories. While complicated and computer intensive, this
analytic structure has been shown to be useful in achieving the goals of the project.
2. ANALYSIS CORE DEVELOPMENT PROJECT 2
DATABASE OF GERIATRIC DATABASES
Ricardo Pietrobon, M.D., Ph.D. - Project Leader
Tel: (919) 668-2054 FAX: (919) 681-8886 E-mail: [email protected]
Funding Years: July 01, 2006 – June 30, 2009
This developmental project is aimed at modifying existing software application for the purposes
of creating a Database of Geriatric Databases. The end product will allow geriatric researchers
to search efficiently, in a single Web-based repository, for information on a large number of
geriatric databases of thematic relevance.
During the first year of funding relevant geriatric databases were reviewed, ranked and
categorized for use in this study. We then developed web-based software that could house the
databases and provide a search mechanism. The application has functionality for uploading new
databases, as well as modifying content for any of the other databases, which are deployed in a
wiki environment
(see User Homepage and database information on the website):
http://200.195.165.4/wikimedic/devel/web/WebDatabaseHTML.php?service=detail&id=6
Upon locating the database, the researcher will find the contact information of the researcher
who posted the database along with information about the database itself and edit functions. All
databases have details regarding total number of observations, age group, data collection
methods, database type, geographical area, interventions, longitudinal variables, pathogenesis,
body system, time period, sampling, requirements for data use, and variable
highlights/uniqueness in relation to other data sets. Register on this page for a username and
password to view the site.
During the development phase, many informal website usability tests were conducted among
researchers. The usability issues that were found in the initial prototype of the software were then
resolved and further tests are currently being conducted. We will continue to improve the site as
it matures over time and will conduct the formal tests during the year to come.
At the end of the development phase, the Database of Geriatric Databases will be initially
released within the Duke Pepper Center for internal testing and evaluation. After initial testing
and modification, the Database of Geriatric Databases will be released to the other participating
Pepper Centers. After one year, a Web survey will be conducted across all centers. Support
from the Pepper Center Coordinating Center at Wake Forest, headed by Dr. Kritschevski has
been ensured for this project.
There has been ongoing testing and further development of the Database of Geriatric Databases.
The database now opens to users without the need of a password. Currently 103 databases are
available on the repository. An online tutorial video was created to demonstrate how to use the
database. We are broadening the scope of the database to include databases outside of
Geriatrics with future plans to expand the number of databases included in the Web-based
repository. We continue to make necessary upgrades to the repository based on user feedback.
We continue to give presentations on how to use the Web-tool.
3. BIOLOGICAL STUDIES CORE DEVELOPMENT PROJECT 1
PROTEIN RACEMIZATION AS A BIOMARKER FOR BIOLOGICAL AGE
Virginia B. Kraus, M.D., Ph.D. - Project Leader
Tel: (919) 681-6652 FAX: (919) 684-8907 E-mail: [email protected]
Funding Years: July 01, 2006 – June 30, 2009
The purpose of this development project is to characterize and validate novel biomarkers of
biological age that are based on protein racemization and isomerization. We hypothesized that
racemization and isomerization of select proteins will be a predictive measure of functional
status and morbidity with an emphasis on osteoarthritis (OA). To test these hypotheses there are
three specific aims:
1) Characterize levels of racemized and isomerized aspartate (Asp) residues in OA patient body
fluids and tissue samples for correlation with chronological age, OA severity, and functional
status by WOMAC index.
2) Identify protein residue "hot spots" susceptible to Asp racemization and isomerization during
aging within cartilage macromolecules, collagen II and aggrecan.
3) Assess the utility of specific protein epitopes containing racemized/isomerized Asp as
biomarkers predictive of functional decline through evaluation of the POP cohort samples at
baseline and correlation with functional status at baseline and three years (radiographic severity
of knee osteoarthritis and WOMAC index at baseline and three years; with grip strength, and
'EPESE' functional battery at three years).
4. BIOLOGICAL STUDIES CORE DEVELOPMENT PROJECT 2
TARGETED METABOLOMICS FOR SPHINGOLIPIDS AND OTHER LIPID-DERIVED
SPECIES
James R. Bain, Ph.D. - Project Leader
Tel: (919) 479-2320 FAX: (919) 477-0632 E-mail: [email protected]
Funding Years: July 01, 2006 – June 30, 2008
Comprehensive metabolomic profiling has the potential to provide novel insights into the
processes of functional decline and degeneration associated with aging. There is growing
evidence that aging and functional decline might involve alterations in lipid metabolism, but
details of these changes remain to be established. The overarching purpose of this development
project is to enhance our capabilities for analysis of lipid metabolism in bodily fluids and tissue
samples from animal models and human subjects. Our three aims are directed at developing
quantitative, high-throughput assays of several key classes of lipids that have heretofore been
difficult and cumbersome to measure:
(1) Develop an assay of fatty acyl coenzyme As of different chain length and degree of
saturation.
(2) Develop assays of ceramides and related sphingolipids.
(3) Apply these assays to tissues sampled by intra- and extramural Pepper investigators.
C. PILOT PROJECTS – YEAR 1 (1992) TO PRESENT (2010)
Double-Blind, Randomized Pilot Study Evaluating the Effect of D-Amphetamine on Motor
Recovery in Patients with Ischemic Stroke
Larry Goldstein, M.D., Assistant Professor
(Funded 1992-93)
Lumbosacral Osteoarthritis in the Elderly: Examining Pain as a Mediator of Progression
from Pathology to Disability
Debra Weiner, M.D., Assistant Professor of Medicine
(Funded 1992-93)
Patient Preferences for Treatment and Outcomes of Rheumatoid Arthritis
Douglas McCrory, M.D., Associate Professor
(Funded 1992-93)
The Personal Functional Goals Interview Protocol: A Refinement and Validation Study
Julie Chandler, Ph.D., P.T., Research Development Core Awardee
(Funded 1993-94)
Development of a New Clinical Scale for Parkinson’s Disease
Toni Cutson, M.D., Assistant Professor
(Funded 1993-94)
Relationship between Body Mass Index and Functional Status
Tony Galanos, M.D., Assistant Professor
(Funded 1993-94)
Increased Resistance to Artificially Induced Carious Lesions in Root Surfaces
Lynn Hobin, D.M.D., Geriatric Dental Fellow
(Funded 1993-94)
A Randomized Controlled Trial of Pulmonary Rehabilitation
Mark Stanton, M.D., Assistant Professor
(Funded 1993-94)
Community Based African/Aerobic Exercise Intervention to Improve Cardiovascular
Fitness, Exercise Adherence, and Psychological Well-being, and Reduce Blood Pressure
and Weight in Older, African-Americans
Maya McNeilly, Ph.D., Assistant Research Professor
(Funded 1993-94)
Evaluation of Pain Behavior Detection by Long Term Care Facility Nursing Personnel
Amrit Singh, M.D., Geriatric Fellow
(Funded 1994-95)
Apolipoprotein E. Allele Frequency in Patients with Cognitive Deficits
Following Cardiopulmonary Bypass
Barbara Tardiff, M.D., Fellow, Cardiac Anesthesia
(Funded 1994-95)
Weight Change in Alzheimer’s Disease: An Analysis of Morbidity, Mortality
and Associated Factors
Heidi White, M.D., Associate Professor
(Funded 1994-95)
The Genetic Aspects of Osteoporosis in Elderly African-Americans and Caucasians
Michael Econs, M.D., Assistant Professor of Medicine
(Funded 1994-95)
A Comparison of the Effects of Fitness and Acute Exercise on the Sleep of Older Women
Miriam C. Morey, M.A., Associate in Research
(Funded 1991-92)
Interference with the Role of Sphingomyelinase in Cell Senescence: An Anti-Aging
Strategy
Miriam Smyth, M.D., Assistant Research Professor
(Funded 1994-96)
A Pilot Study for a Clinical Trial to Evaluate the Effects of Paroxetine on Transient
Myocardial Ischemia and Cardiac Events in Older Patients with Coronary Disease
Accompanied by Depression
Wei Jiang, M.D., Research Associate
(Funded 1994-95)
Genetic Studies of Familial Forms of Osteoarthritis
Virginia B. Kraus, M.D., Assistant Professor
(Funded 1994-95)
Getting Meaningful Informed Consent for Research in the Elderly:
Literature Review of Empirical Research
Jeremy Sugarman, M.D., M.P.H., M.A., Assistant Professor
(Funded 1995-96)
A Structured
Genetic Studies in Paget’s Disease of Bone
Michael J. Econs, M.D., Assistant Professor
(Funded 1995-96)
The Relationship of Age with Indicators of Oxidative Status: A Potential Opportunity for
Studying Aging Process and Life-Style Factors Which Affect It
Connie Bales, Ph.D., Associate Research Professor
(Funded 1995-96)
The Effects of Long Term Psychologic Intervention on Functional Status of Patients with
Heart Failure
Martin Sullivan, M.D., Associate Professor
(Funded 1995-96)
Effect of Aging on Acute Myocardial B-Adrenergic Receptor Desensitization During
Cardiopulmonary Bypass
Debra A. Schwinn, M.D., Associate Professor
(Funded 1995-96)
Screening Elderly Primary Care Patients for Diabetes
David Edelman, M.D., Associate Professor
(Funded 1999-00)
Cellular Aging and Extra Cellular Antioxidants
Rodney J. Folz, M.D., Ph.D., Assistant Research Professor
(Funded 1999-00)
Genetics of Successful Aging in the Midwestern Amish
William Scott, Ph.D., Assistant Research Professor
(Funded 1999-00)
Effectiveness of PspA Pneumococcal Vaccines in Aged Mice
Gregory Taylor, Ph.D., Assistant Research Professor
(Funded 2000-01)
Age-Related Macular Degeneration
Silke A. Schmidt, Ph.D., Research Scientist
(Funded 2000-01)
Survey of Providers on Cancer Screening in the Elderly
Mitchell Heflin, M.D., Assistant Professor
(Funded 2000-01)
Aging and Immune Response to Surgical Stress and Sepsis
Sandhya A. Lagoo-Deenadayalan, M.D., Research Fellow
(Funded 2000-01)
Developing Expression Proteomics Assays to Study Aging
Dhaval Kumar Patel, M.D., Associate Professor
(Funded 2000-01)
The Role of Age on Mechanical Stress Induced Changes in Matrix Turnover
in Articular Cartilage
Beverly Fermor, Ph.D., Research Associate
(Funded 2001-02)
Web-Based Patient Recruiting for Clinical Trials
David F. Lobach, M.D., Ph.D., M.S., Chief, Divisions of Clinical Informatics
(Funded 2001-02)
Genetic Ascertainment of Large African/Native American Family for Osteoarthritis &
Cardiovascular Disease
Cathleen Colon-Emeric, M.D., Assistant Professor
(Funded 2000-01)
Roles of Age on Mechanical Stress
Virginia Kraus, M.D., Associate Professor
(Funded 2001-02)
Gene Expression Profiling of Murine Models of Atherosclerosis
David Seo, M.D., Research Fellow
(Funded 2002-03)
Depression and Outcomes in Patients with End-Stage Renal Disease on Hemodialysis
Susan Hedayati, M.D., Research Fellow
(Funded 2002-03)
Outcome Analysis of Cervical Spondylotic Myelopathy
Dennis Turner, M.D., Professor, Departments of Surgery and Neurobiology
(Funded 2002-03)
Use of Classification Trees in the Diagnosis of Mild Cognitive Impairment and Dementia
Maragatha Kuchibhatla, Ph.D., Geriatrics
(Funded 2002-03)
Hospital-Acquired Infections in the Elderly
Keith S. Kaye, M.D., MPH, Assistant Professor, Infectious Diseases, Department of Medicine
(Funded 2003-04)
Cultural Differences in End-of-Life Care: The African-American Experience
Kimberly Johnson, M.D., Associate
(Funded 2004-05)
Executive Function and Ambulatory Activity in Older Adults
James T. Cavenaugh, PT, Ph.D., Assistant Research Professor
(Funded 2006-07 and 2007-08)
Lipid Induced Mitochondrial Dysfunction and Age-Related Insulin Resistance
Deborah Muoio, Ph.D., Assistant Professor
(Funded 2006-07 and 2007-08)
Gene-Environment Interactions in Aging, Functional Decline and Disease
Svati H. Shah, M.D., M.H.S. Assistant Professor, Department of Medicine, (Epidemiology)
M.H.S. (Medical Genomics)
(Funded 2006-07 and 2007-08)
Strength and Gait Training for Older Adults with Knee Osteoarthritis and Varus
Malalignment
Kelli Dominick Allen, B.S., M.S., Ph.D., Associate Research Professor Division of General
Internal Medicine
(Funded 2008-10)
Positive Emotion and Functioning in Older Adults
Beverly H. Brummett, B.S., M.A., Ph.D., Associate Research Professor, Department of
Psychiatry
(Funded 2008-10)
Genetic Factors and Differential Response of the Elderly to Ozone: Effects on Lung
Function, and Epithelial Integrity
William M. Foster, B.A., M.S., Ph.D., Professor, Department of Medicine
(Funded 2008-10)
Aerobic Exercising Training and Attenuation of the Susceptibility of Older Adults to
Endotoxin-Induced Lung Injury (Small Exploratory Study)
Amy Pastva, PT Ph.D., Medical Instructor, Department of Physical Therapy
(Funded 2009-10)
Aging, Inflammatory Markers and Obesity (Small Exploratory Study)
Tim Koves, Ph.D., Assistant Research Professor, Department of Medicine, Geriatrics Division
(Funded 2009-10)
The Role of Oxidative Stress in Metabolism and Physical Performance
(Small Exploratory Study)
Helen Lum, Fellow, Department of Medicine, Geriatrics Division.
(Funded 2009-10)
Characterizing Age-related Post Translational Protein Modifications by Mass
Spectroscopy (Administrative Supplement)
Virginia Kraus, MD, PhD, Professor of Medicine, Division of Rheumatology & Immunology
(Funded 2009-2010)
Identifying Epigenetic Targets of Aging and Atherosclerosis (Administrative Supplement)
Elizabeth Hauser, PhD, Center for Medicine Genetics, Department of Medicine
Funded (2009-2010)
Elevated Plasma Nitrite via Dietary Nitrate Supplementation and Its Effects On Vascular
Endothelial Function and Physical Function in the Elderly, (Small Exploratory Study)
Jason Allen, PhD, Assistant Professor, Department of Medicine
(Funded 2009-2010)
Effect of Aerobic Training on Cardiopulmonary Function and Quality of Life in
Postsurgical Lung Cancer Patients, (Small Exploratory Study)
Lee Jones, PhD., Associate Professor, Duke Comprehensive Cancer Center
(Funded 2009-2010)
Role of Aging and Endoplasmic Reticulum Stress in the Pathogenesis of Pulmonary
Fibrosis, (Small Exploratory Study) Jessica Chia, MD., Department of Medicine
(Funded 2009-2010)
Neuronal Dysregulation and Disintegration in Function in Frail Older Adults, (Small
Exploratory Study) David Madden, PhD, Professor, Department of Psychiatry and Behavioral
Sciences
(Funded 2009-2010)
Impact of Zoledronic Acid on Immune Function in Aged and Young Mice, (Small
Exploratory Study) Greg Sempowski, PhD., Associate Professor, Department of Medicine
(Funded 2009-2010)
The Relationship of Gait to Age, Muscle Strength and Endurance in a Mouse Model with
Partially Blunted of Fatty Acid Oxidation, (Small Exploratory Study) Tim Koves, Ph.D.,
Assistant Research Professor, Department of Medicine, Geriatrics Division
(Funded 2009-10)
D. COMPLETED INTERVENTION /INTERVENTION DEVELOPMENT STUDIES
Disability and Osteoporosis in Life-Care Community Women (IS)
Deborah Gold, Ph.D., Project Leader
Funding Years 1992-1999
Aerobic vs. Axial/Aerobic Exercise: Improvement in Function (IS)
Miriam C. Morey, Ph.D., Project Leader
Funding Years 1992-1999
Exercise, Axial Mobility and Function in Chronically Institutionalized Long-Term
Care Patients (IDS)
Gary Kochersberger, M.D., Project Leader
Funding Years 1992-1999
Eleanor McConnell, Ph.D., R.N., Co-Project Leader
Funding Years 1992-1996
Axial Mobility Exercises for Parkinson’s Patients (IDS)
Margaret Schenkman, Ph.D., Project Leader
Funding Years 1992-1999
Hip Bone Density in Elderly African American Women (Supplemental Project)
Arline Bohannon, M.D., Project Leader
Funding Years 1994-1996
Phoning For Function: Promoting Health After Cancer
Wendy-Demark-Wahnnefried, Ph.D., Project Leader
Funding Years 1999 - 2004
Taste and Smell Enhancement in Older Cancer Patients
Susan Schiffman, Ph.D., Project Leader
Funding Years 1999 – 2004
Finding the Right Wheels: Improving Wheelchair Provision
Helen Hoenig, M.D., Project Leader
Funding Years 1999 - 2004
Quantitative Serum Traits in the Genetics of Osteoarthritis
Virginia Kraus, M.D., Ph.D., Project Leader
Funding Years 1999 - 2004
SECTION III. CAREER DEVELOPMENT SUBSEQUENT TO PEPPER CENTER
FUNDING: YEAR 2003 TO PRESENT
Kenneth E. Schmader, M.D., Associate Professor of Medicine
Duke University Medical Center VA Medical Center,
Durham, NC
Grants Awarded:
National Institute on Aging Academic Award
2 Industry Sponsored Studies
K-24 (Funded September 1, 2001 – May 31, 2008)
Delanie W. Kitzman, M.D., Assistant Professor of Medicine
Bowman Gray School of Medicine, Wake Forest University
Grants Awarded:
NIH R01 – Effect of Exercise Training on Diastolic Dysfunction, PI
Supplement to R01
Hypergen: Genetics of Left Ventricular Hypertrophy PI, Bowman Gray School of Medicine
Field Site
William M. McDonald, M.D., Assistant Professor of Psychiatry
Emory University
Grants Awarded:
Parasuicide in Nursing Home Residents (National Suicide Foundation) PI
Pallidotomy and Parkinson Disease (NIH) - CoI
Alzheimer's Registry (NIH) CoI
Douglas C. McCrory, M.D., M.H.Sc, Associate Professor of Medicine
Duke University Medical Center & VA Medical Center,
Durham, NC
Grants Awarded:
Development of Clinical Practice Guidelines: Headaches (AHCPR)
Julie M. Chandler, Ph.D., PT
Senior Epidemiologist Merck Research Laboratories
Debra K. Weiner, M.D., Assistant Professor of Medicine
University of Pittsburgh Medical Center
Pittsburgh, PA
Grant Awarded:
NIA Academic Award
Arline D. Bohannon, M.D., Division of General Internal Medicine,
Virginia Commonwealth University Medical Center, Richmond, VA
Associate Director of Research, Geriatric Research, Education and Clinical Center, Department of
Veterans Affairs Medical Center, Durham, NC
Grants Awarded:
Minority Supplement Duke Univ. Pepper OAIC (PI)
NIEHS Environmental Toxicology Fellowship
Helen M. Hoenig, M.D., Associate Professor of Medicine
VA Medical Center and Duke University Medical Center,
Durham, NC
Grants Awarded:
VA Merit Grant (PI)
HSR&D Rapid Development Project Grant (Co PI)
Beeson Award 1997-2000
Larry B. Goldstein, M.D., Professor of Medicine (Neurology)
Duke University Medical Center
Durham, NC
Grants Awarded:
Duke University Small Grant (PI)
3 Industry Sponsored Studies
Stroke PORT AHCRP
Clinical Practice Guidelines from Chronic Pain: Headaches
AHCPR
Maya McNeilly, Ph.D.
Private Practice, Durham, NC
Grant Awarded:
Opioid Compromise in Hypertension: Modulating Factors (NIH) PI
Effects of Stress on Sodium Excretion, Blood Pressure In Older African Americans CoPI
Michael J. Econs, M.D.
Indiana University Medical Center
Grant Award:
FIRST Award NIH
Miriam J. Smyth, PhD
University of Maryland
Grant Awarded:
Duke University Medical Center Small Research Grant
Research Grant Institutional Grant Award to Duke University from American Cancer Society
Wei Jiang, M.D., Research Associate in Medicine
Duke University Medical Center
Durham, NC
Grant Awarded:
SAD Heart Study (Peizer Pharmaceutical) CoPI
Virginia B. Kraus, M.D., Ph.D., Associate Professor of Medicine;
Assistant Professor , Pathology; and Assistant Professor, Surgery
Duke University Medical Center
Durham, NC
Grants Awarded:
Arthritis Investigator Award (PI) - Arthritis Foundation
Early Career Development Award (PI American Federation for Aging Research Grant (PI)
RO1
Barbara E. Tardiff, M.D., M.S., Assistant Consulting Professor of Anesthesiology
Duke University Medical Center
Durham, NC
Grant Awarded:
A Randomized Trial of SPM 633 to Prevent Renal Impairment in CABG Patients (Schwartz
Pharmaceuticals)
Dose Ranging Study of hBNP After CABG Surgery (SCIOS) PI
Effect of Integrin on Platelet Aggregation ( ) Site PI
William E. Kraus, M.D., Associate Professor of Medicine & Cell Biology
Duke University Medical Center
Durham, NC
Grants Awarded:
Molecular Events Promoting Phenotypic Transformation of Skeletal Muscle During Exercise
Training (PI)
American Heart Association (PI)
Molecular Signaling in Muscular Adaptation to Exercise NIAMS (PI)
SCOR In Heart Failure NHLBI (CoPI)
Regulation of Skeletal Muscle Development and Differentiation In Vitro by Mechanical and
Chemical Factors NASA (PI)
Jeremy Sugarman, M.D., Professor of Medicine,
Johns Hopkins
Grants Awarded:
SPORE in Breast Cancer, NCI (CoPI)
Ethical Aspects of Umbilical Cord Banking NHLBI (CoPI)
James A. Tulsky, M.D., Associate Professor of Medicine
Duke University Medical Center & VA Medical Center,
Durham, NC
Grants Awarded:
SOROS Faculty Scholar (PI)
AHRP-Andrus Foundation (PI)
Greenwald Foundation(PI)
Open Society Institute (CoPI)
David Edelman, M.D., Assistant Professor, General Internal Medicine
Duke University Medical Center
Durham, NC
Grants Awarded:
VA Health Services Research Career Award
AHRQ Award
HSRA Training Grant
2 Industry Grants
VA HSRD Grant: “Screening Elderly Primary Care Patients for Diabetes”
Rodney Folz, M.D., Ph.D., Associate Professor, Medicine; and Asst. Research Professor,
Cell Biology,
Duke University Medical Center,
Durham, NC
Grant Awarded:
1 NIH RO1 grant
William Scott, Ph.D., Associate Research Professor
Medicine—Medical Genetics
Duke University Medical Center
Durham, NC
Grant Awarded:
1- NIH – RO1 Grant: Genetics of Successful Aging in Midwestern Amish
Hilary Grocott, M.D., Assistant Professor, Anesthesiology-Cardiac Division,
Duke University Medical Center
Durham, NC
Grants Awarded:
New Investigator Award, Foundation for Anesthesia Education Research/ American Geriatrics
Society 2001-2003; Co-Investigator,
Biosite Diagnostics Inc., 1999-2001
Cathleen S. Colon Emeric, M.D., Assistant Professor, Medicine,
Duke University Medical Center
Durham, NC
Grant Awarded:
Brookdale Fellowship 2001-2003
“Osteoarthritis & Cardiovascular Disease”
Mitchell T. Heflin, M.D., Assistant Professor, Medicine,
Duke University Medical Center
Durham, NC
Grants Awarded:
Pfizer/AGS Health Services Research Fellowship
Geriatric Career Development Award
Beverly Fermor, Ph.D., Assistant Research Professor
Surgery – Orthopaedic Surgery
Duke University Medical Center
Durham, NC
Grants Awarded:
1 NIH R01,
1 Industry Grant
1 NIH R03
Sandhya A. Lagoo-Deenadayalan, M.D., Ph.D., Assistant Professor
Surgery – General
Duke University Medical Center
Durham, NC
Grants Awarded:
1 AGS Jahnigen Award
1 NIH K08 Submitted
1 NIH R21 Submitted
Aging and Immune Response to Surgical Stress and Sepsis
David F. Lobach, M.D., Ph.D., Associate Professor
Community & Family Medicine – Informatics
Clinical Associate, Division of Endocrine & Metabolic Medicine
Duke University Medical Center
Durham, NC
Grants Awarded:
1 Industry Grant
1 NIH R01 Submitted
1 HSRA Grant Submitted
Gregory A. Taylor, Ph.D., Assistant Research Professor
Medicine – Geriatrics
Duke University Medical Center
Durham, NC
Grants Awarded:
1 NIH R01 Grant
1 VA Merit Review
“Effectiveness of PspA Pneumococcal Vaccines In Aging Mice”
Silke A. Schmidt, Ph.D., Assistant Science Research Professor,
Medicine – Genetics Division,
Duke University Medical Center
Durham, NC
Grants Awarded:
1 NIH / NEI Grant
“Genetic and Epidemiologic Risk Factors in Age-Related Macular Degeneration”
Virginia B. Kraus, M.D., Ph.D., Associate Professor of Medicine;
Assistant Professor , Pathology; and Assistant Professor, Surgery
Duke University Medical Center
Durham, NC
Grants Awarded:
Josiah Charles Trent Memorial Foundation Grant
Mary Biddle Duke Grant
1 NIH R01 Grant
1 NIH R01
Pilot Study: “Genetic Ascertainment of a Large African-American / Native American Family for
Osteoarthritis and Cardiovascular Disease”
David M. Seo, M.D., Assistant Professor, Medicine-Cardiology
Duke University Medical Center
Durham, NC
Grant Awarded:
1 NIH R01 Grant submitted, review pending NIH K12 funding
James T. Cavanaugh PT, Ph.D., Assistant Research Professor,
Medicine – Geriatrics Division
Duke University Medical Center
Durham, NC
Grant Awarded:
VA Associate Investigator Award
“Rehabilitation Research and Development Service”
NIA – R21
“Walking Activity and the Burden of Multiple Morbidities
Duke Community and Family Medicine Small Grant
“Physical Activity and Recovery Postpartum”
Kim Huffman, M.D., Medical Instructor,
Department of Rheumatology and Immunology
Duke University Medical Center
Durham, NC
K-23
American College of Rheumatology – Research Education Foundation /Association
of Subspecialty Professors Junior Career Development Award in Geriatrics Medicine
part of the T. Franklin Williams Scholars Program
Keith Kaye, M.D., Associate Professor – Medicine, Infectious Disease
Duke University Medical Center
Durham, NC
Grant Awarded:
1-NIA K23
“Hospital Acquired Infections in the Elderly”
Jama L. Purser, PT, Ph.D., Assistant Research Professor
Medicine – Geriatrics Division
Duke University Medical Center
Durham, NC
Grant Awarded:
(Funded May, 2006- April, 2011)
K01 Mentored Research Scientists Career Development Award
NICHHD “Candidate Genes and Longitudinal Disability Phenotypes”
Deborah M. Muoio, Ph.D., Assistant Professor
Medicine – Endocrinology & Metabolomics
Duke University Medical Center
Durham, NC
Grant Awarded:
K-01
(Funded July 2004 – June, 2008)
Heather E. Whitson, M.D. – Assistant Professor, Division of Geriatrics
Duke University Medical Center
Durham, NC
Grant Awards:
Paul B. Beeson Career Development Award (Funded September, 2008 – June, 2013)
Matthew Peterson, Ph.D.- Assistant Professor, Division of Geriatrics
Duke University Medical Center
Durham, NC
Grant Awards:
VA Career Development Award (Funded May, 2008 – July, 2010)
Thomas Povsic , MD, Assistant Professor
Medicine – Cardiology
Duke University Medical Center
Durham, NC
Grant Awards:
Merck-Society of Geriatric Cardiology Research Award
MEDUSA- Medtronic-Duke Strategic Alliance Research Award
Duke Clinical Research Institute Research Award
SECTION IV.
DUKE PEPPER CENTER PUBLICATIONS - 1991-2010
JOURNAL ARTICLES, BOOKS, AND BOOK CHAPTERS
PUBLISHED
1991
Blumenthal, J. A., Emery, C. F., Madden, D. J., Schniebolk, S., Riddle, M. W., Cobb, F. R.,
Higginbotham, M. B., & Coleman, R. E. (1991). Effects of exercise training on bone density in
older men and women. Journal of the American Geriatrics Society, 39, 1065-1070.
Kitzman, D., Sheikh, K., Beere, P., Philips, J., & Higginbotham, M. (1991). Age-Related
Alterations of Doppler Left Ventricular Filling Indexes in Normal Subjects are Independent of
Left Ventricular Mass, Heart Rate, Contractility and Loading Conditions. J Am Coll Cardiol,
18(5), 1243-1250.
Krucoff, M. W., Higginbotham, M. B., Van Trigt, P., Sawchak, S. T., Jones, R. H., Wall, T. C.,
Phillips, H. R., Stack, R. S., & Reeves, J. G. (1991). From HIRMIT to the Cape May Lighthouse.
Revascularization Reconsidered in Very High Risk Patients at the Duke Heart Center. N.C. Med
J, 52(12).
Weiner, D. K., & Allen, N. B. (1991). Large Vessel Vasculitis of the Central Nervous System in
Systemic Lupus Erythematosus: Report and Review of the Literature. J Rheumatol, 18, 748-751.
1992
Anderson, N. B., McNeilly, M., & Myers, H. (1992). Toward Understanding Race Differences in
Reactivity: A Proposed Contextual Model. In R. Turner, A. Sherwood, & K. C. Light (Eds.),
Individual Differences in Cardiovascular Responses to Stress (pp. 12-140): Plenum.
Blazer, D. G. (1992). Geriatric Psychiatry in the United States: The Clinical Investigation,
Diagnosis and Treatment of Late Life Depression as an Example. Psychiatria Hungarica, 7(6),
605-613.
Blazer, D. G., Hughes, D., & George, L. (1992). Age and Impaired Subjective Support:
Predictors of Depressive Symptoms at One-Year Follow-up. J Nerv Ment Dis, 180(3), 172-178.
Duncan, P., Studenski, S., Prescott, B., & Chandler, J. (1992). Assessment of Falls in the Elderly.
Physical Therapy Practice, 1(1), 69-76.
Econs, M. J., Barker, D. F., Speer, M. C., Pericak-Vance, M. A., Fain, P. R., & Drezner, M. K.
(1992). Multilocus Mapping of the X-linked Hypophosphatemic Rickets Gene. J Clin
Endocrinol Metab, 75, 201-206.
Hanlon, J. T., Schmader, K. E., Samsa, G. P., Weinberger, M., Uttech, K., Cohen, H. J., &
Feussner, J. R. (1992). A Method of Assessing Drug Therapy Appropriateness. J Clin
Endocrinol, 45, 1045-1053.
Koenig, H. G., Cohen, H. J., & Blazer, D. G. (1992). Religious Coping and Depression Among
Elderly Hospitalized Medically Ill Men. Am J Psychiatry, 149, 1693-1700.
Koenig, H. G., Cohen, H. J., Blazer, D. G., Meador, K. G., & Westlund, R. (1992). A Brief
Depression Scale for Use in the Medically Ill. Int J Psychiatry Med, 22, 183-195.
Manos, P. A., & Schenkman, M. (1992). Rehabilitation Management of a Geriatric Individual
with Neurologic and Pulmonary Dysfunction: A Case Analysis. Top Geriatric Rehabilitation,
7(4), 36-54.
Morey, M., DiPasquale, R., Crowley, G., & Sullivan, R. (1992). The Gerofit Workout: An
Exercise Manual for Older Adults. Durham, NC: GRECC, Durham VA Medical Center.
Roses, A. D., Pericak-Vance, M. A., Alberts, M. J., Saunders, A. M., Taylor, H., Gilbert, J.,
Schwartzbach, C., Peacock, M., Fink, J., Bhasin, R., & Goldgaber, D. (1992). Locus
heterogeneity of Alzheimer's disease. Proceedings of the Foundation IPSEN pour la Recherche
Therapeutique of France: Heterogeneity of Alzheimer's Disease, 101-117.
Schaie, K. W., Blazer, D., & House, J. S. (1992). Aging, Health Behaviors, and Health
Outcomes: Lawrence Erlbaum Associates, Inc.
Schenkman, M. (1992). Physical Therapy Intervention for the Ambulatory Patient. In C.
Turnbell (Ed.), Physical Therapy Management in Parkinson's Disease . New York: Churchill
Livingstone.
Schmader, K. E., Rahija, R., Porter, K. R., Daley, G., & Hamilton, J. D. (1992). Aging and
Reactivation of Murine Cytomegalovirus. J Infect Dis, 166, 1403-1407.
St. George-Hyslop, P., Haines, J., Rogeav, E., Mortilla, M., Vaula, G., Pericak-Vance, M. A.,
Foncin, J. F., Montesi, M., Bruni, A., Sorbi, S., Rainero, I., Pinessi, L., Pollen, D., Polinsky, R.,
Nee, L., Kennedy, J., Macciardi, F., Rogaeva, E., Liang, Y., Alexandrova, N., Lukiw, W.,
Schlumpf, K., Tanzi, R., Tsuda, T., Farrer, L., Cantu, J. M., Duara, R., Amaducci, L., Bergamini,
L., Gusella, J., Roses, A. D., & Crapper McLachlan, D. (1992). Genetic Evidence for a Novel
Familial Alzheimer's Disease Locus on Chromosome 14. Nature Genetics, 2, 330-334.
Suarez, E. C., & Williams, R. B. (1992). Chapter 10: Interactive Models of Reactivity: The
Relationship Between Hostility and Potentially Pathogenic Physiological Responses to Social
Stressors. In N. Schneiderman, P. McCabe, & A. Baum (Eds.), Stress and Disease Processes .
Hillsdale, NJ: Lawrence Erlbaum Associates.
Tweed, D., Blazer, D., & Ciarlo, J. (1992). Psychiatric Epidemiology in Elderly Populations. In
R. B. Wallace & R. F. Woolson (Eds.), The Epidemiologic Study of the Elderly . New York:
Oxford University Press.
Weiner, D. K., Duncan, P. W., Chandler, J., & Studenski, S. A. (1992). Functional Reach: A
Marker of Physical Frailty. J Am Geriatr Soc, 40, 203-207.
Williams, R. B., Barefoot, J. C., Califf, R. M., Haney, T. L., Saunders, W. B., Pryor, D. B.,
Hlatky, M. A., Siegler, I. C., & Mark, D. B. (1992). Prognostic Importance of Social and
Economic Resources Among Medically Treated Patients With Angiographically Documented
Coronary Artery Disease. JAMA, 267, 520-524.
1993
Anderson, N. B. (1993). Reactivity Research on Sociodemographic Groups: Its Value to
Psychophysiology and Health Psychology. Health Psychol, 12, 3-5.
Anderson, N. B., McNeilly, M., & Myers, H. (1993). A Biopsychosocial Model of Race
Differences in Vascular Reactivity. In J. Blascovich & E. S. Katkin (Eds.), Cardiovascular
Reactivity to Psychological Stress and Disease (pp. 83-108): American Psychological
Association.
Anderson, N. B., & McNeilly, M. (1993). Autonomic Reactivity and Hypertension in Blacks:
Toward a Contextual Model. In J. S. Fray & J. Douglas (Eds.), The Pathophysiology of
Hypertension in Blacks (pp. 107-139): Oxford University Press.
Barefoot, J. C., Lipkus, I. M., Feaganes, J., Williams, R. B., & Siegler, I. C. (1993). Emotionality
in Adolescence Predicts Substance Use at Mid-Life. Ann Behav Med, 15, 50.
Blazer, D. B. (1993). Neurotic Disorders: Epidemiology. In J. R. M. Copeland, M. T. AbouSaleh, & D. G. Blazer (Eds.), The Psychiatry of Old Age . London: John Wiley & Sons Ltd.
Blazer, D. G. (1993). Depression in Late Life. St. Louis: CV Mosby.
Chandler, J., Laub, K., Keysor, J., MacAller, H., & Schenkman, M. (1993). Axial Mobility
Exercise Program: A Home Exercise Program to Improve Functional Ability. Durham, NC:
Duke University Claude D. Pepper Older Americans Independence Center.
Corder, E. H., Saunders, A. M., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Small, G.
W., Roses, A. D., Haines, J. L., & Pericak-Vance, M. A. (1993). Gene dose of apolipoprotein E
type 4 allele and the risk of Alzheimer's disease in late onset families. Science, 261, 921-923.
Duke University Center for the Study of Aging and Human Development. (1993, ). Pepper
Center News: The Center Report, 12, 5.
Duncan, P. W., Shumway-Cook, A., Tinetti, M. E., Whipple, R. H., Wolf, S., & Woollacott, M.
(1993). Is There One Simple Measure for Balance. PT Journal, 1(1), 74-80.
Durel, L. A., Kus, L. A., Anderson, N. B., McNeilly, M., Llabre, M. M., Spitzer, S., Saab, P. G.,
Efland, J., Williams, R., & Schneiderman, N. (1993). Patterns and Stability of Cardiovascular
Responses to Variations of the Cold Pressor Test. Psychophysiology, 30, 39-46.
Econs, M., Fain, P., Norman, M., Speer, M., Pericak-Vance, M., Becker, P., Barker, D., Taylor,
A., & Drezner, M. (1993). Flanking markers define the x-linked hypophosphatemic rickets gene
locus. Journal of Bone and Mineral Research, 8, 1149-1152.
Edinger JD, Morey MC, Sullivan RJ, Higginbotham MB, Marsh GR, Dailey DS, & McCall WV
(1993). Aerobic Fitness, Acute Exercise and Sleep in Older Men. Sleep, 16(4), 351-359.
Galanos, A. N., Cohen, H. J., & Jackson, T. W. (1993). Medical Education in Geriatrics: The
Lasting Impact of the Aging Game. Educational Gerontology, 19, 675-682.
Gold, D., Stegmaier, K., Bales, C., Lyles, K., Westlund, R., & Harper, K. (1993). Psychosocial
Functioning and Osteoporosis in Late Life: Results of a Multidisciplinary Intervention. J
Women's Health, 2, 149-155.
Haines, J. L., St. George-Hyslop, P. H., Rimmler, J. B., Yamaoka, L., Kazantsev, A., Tanzai, R.
E., Gusella, J. F., Roses, A. D., & Pericak-Vance, M. A. (1993). Inheritance of Multiple Loci in
Familial Alzheimer Disease. In B. Corain, K. Iqbal, M. Nicolini, B. Winblad, H. Wisniewski, &
P. Zatta (Eds.), Alzheimer's Disease: Advances in Clinical and Basic Research (pp. 221-226).
Chichester, U.K.: John Wiley & Sons.
Hogue, C., Cullinan, S., & McConnell, E. (1993). Exercise Interventions for the Chronically Ill:
Review and Prospects. (eds.), Key Aspects of Caring for the Chronically Ill Hospital and Home.
New York, NY: Springer Publishing Co.
Kitzman, D. W., Higginbotham, M. B., & Sullivan, M. J. (1993). Aging and the Cardiovascular
Response to Exercise. Cardiology in the Elderly, 543-550.
Lyles, K., Gold, D., Shipp, K., & Pieper, C. (1993). Impairments in Patients with Vertebral
Compression Fractures. In C. Christiansen & B. Riis (Eds.), Fourth Annual International
Symposium on Osteoporosis . Riverton NJ: Cahners Publishing Company.
Lyles, K. W., Gold, D. T., Shipp, K. M., Pieper, C. F., Martinez, S., & Mulhausen, P. L. (1993).
Osteoporotic Vertebral Compression Fractures: Their Association with Impaired Functional
Status. American Journal of Medicine, 94(6), 595-601.
Saunders, A. M., Schmader, K. E., Breitner, J., Benson, M. D., Brown, W. T., Goldfarb, L.,
Goldgabar, D., Manwaring, M. G., Szymanski, M. H., McCowan, N., Dole, K. C., Schmechel, D.
E., Strittmatter, W. J., Pericak-Vance, M. A., & Roses, A. D. (1993). Apolipoprotein E4 Allele
Distributions in Late-onset Alzheimer Disease and in Other Amyloid-forming Diseases. Lancet,
342, 710-713.
Saunders, A. M., Strittmatter, W. J., Schmechel, D., St. George-Hyslop, P. H., Pericak-Vance,
M. A., Joo, S. H., Rosi, B. L., Gusella, J. F., Crapper-MacLachlan, D. R., Growden, J., Alberts,
M. J., Hulette, C., Crain, B., Goldbager, D., & Roses, A. D. (1993). Association of
Apolipoprotein E Allele 4 with Late-onset Familial and Sporadic Alzheimer's Disease.
Neurology, 43, 1467-1472.
Schenkman, M. (1993). Part 1: To Unlock the Logic of Evaluation. Making Decisions. PT
Magazine, 57-60.
Schenkman, M. (1993). Part 2: To Put Logic Into Action. Making Decisions. PT Magazine, 6163.
Strittmatter, W. J., Saunders, A. M., Schmechel, D., Pericak-Vance, M., Enghild, J., Salvesen, G.
S., & Roses, A. D. (1993). Apolipoprotein E: High Avidity Binding to b-Amyloid and Increased
Frequency of Type 4 Allele in Late-onset Familial Alzheimer's Disease. Proc Natl Acad Sci, 90,
1977-1981.
Suarez, E. C., Harlan, E., Peoples, M. C., & Williams, R. B. (1993). Cardiovascular and
Emotional Responses in Women: The Role of Hostility and Harassment. Health Psychol, 12(6),
459-468.
Weiner, D. K., Bongiorni, D. R., Studenski, S. A., Duncan, P. W., & Kochersberger, G. G.
(1993). Does Functional Reach Improve with Rehabilitation. Arch Phys Med Rehabil, 74, 796800.
Weiner, D. K., Long, R., Hughes, M. A., Chandler, J., & Studenski, S. (1993). When Older
Adults Face the Chair Rise Challenge. J Am Geriatr Soc, 41, 6-10.
Williams, R. B. (1993). Psychosocial Factors and Prognosis in Established Coronary Artery
Disease. J Am Med Assoc, 270(15), 1860-1861.
Williams, R. B., Barefoot, J. C., Blumenthal, J. A., Helms, M. J., Pieper, C. F., Siegler, I. C.,
Stallone, L., & Suarez, E. C. (1993). Psychosocial Correlates of Job Strain in a Sample of
Working Women. Ann Behav Med, 15, 72.
Zonderman, A. B., Siegler, I. C., Barefoot, J. C., Williams, R. B., & Costa, P. T. (1993). Age and
Gender Differences in the Content Scales of the Minnesota Multiphasic Personality Inventory.
Experi Aging Res, 19, 241-257.
1994
Barefoot, J. C., Patterson, J. C., Haney, T. L., Cayton, T. G., Hickman, J. R., Jr., & Williams, R.
B. (1994). Hostility in Asymptomatic Men with Angiographically Confirmed Coronary Artery
Disease. American Journal of Cardiology, 74, 439-442.
Bearon, L., Crowley, G., Chandler, J., Robbins, M., & Studenski, S. (1994). Personal Functional
Goals: A New Approach to Assessing Patient-relevant Outcomes. The Gerontologist, 34, 239240.
Beckham, J. C., Barefoot, J. C., Haney, T. L., Williams, R. B., & Mark, D. B. (1994). Pain
Coping Strategies in Patients Referred for Evaluation of Angina Pectoris. Journal of
Cardiopulmonary Rehabilitation, 14, 1-8.
Bohannon, A. D., & Lyles, K. W. (1994). Drug Induced Bone Disease in the Elderly. Clinics of
Geriatric Medicine, 10(4), 611-623.
Cohen, H. (1994). Biology of aging as related to cancer. Cancer, Supplement 74(7), 2092-2100.
Corder, E. H., Saunders, A. M., Risch, N. J., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C.,
Rimmler, J. B., Locke, P. A., Conneally, P. M., Schmader, K. E., Small, G. W., Roses, A. D.,
Haines, J. L., & Pericak-Vance, M. (1994). Apolipoprotein E type 2 allele decreases the risk on
late onset Alzheimer disease. Nature Genetics, 7, 180-184.
Cutson, T. M. (1994). Assessment of Motor Planning Deficits. Top Geriatric Rehab, 10(2), 5269.
Duncan, P. W., & Studenski, S. (1994). Balance and Gait Measures. Ann Rev of Gerontol
Geriatr, 14, 76-92.
Galanos, A., Pieper, C., Cornoni-Huntley, J., Fillenbaum, G., & Bales, C. (1994). Nutrition and
Function: The Relationship of Body Mass Index to the Daily Activities of Community Dwelling
Elderly. J Am Geriatr Soc, 42, 368-373.
Galanos, A., Strauss, R., & Pieper, C. (1994). Sociodemographic Correlates of Health Beliefs
Among Black and White Community Dwelling Elderly. The International Journal of Aging and
Human Development, 38(4), 277-288.
Galanos, A. N., Fillenbaum, G. G., Cohen, H. J., & Burchett, B. M. (1994). The Comprehensive
Assessment of Community Dwelling Elderly: Why Functional Status is Not Enough. Aging:
Clinical and Experimental Research, 6, 343-352.
Galanos, A. N., Pieper, C. F., Cornoni-Huntley, J. C., Bales, C. W., & Fillenbaum, G. G. (1994).
Nutrition and Function: Is There a Relationship Between Body Mass Index and Functional
Capabilities of Community Dwelling Elderly? Journal of the American Geriatrics Society, 42,
368-373.
Gautier, M., & Cohen, H. J. (1994). Multiple Myeloma in the Elderly. J Am Geriatr Soc, 42,
653-664.
George, L. K. (1994). Multidimensional Assessment Instruments: Present Status and Future
Prospects. Annual Review of Gerontology and Geriatrics, 14, 353-375.
Gold, D. T. (1994). Chronic Musculoskeletal Pain: Older Women and Their Coping Strategies.
In K. A. Roberto (Ed.), Older Women With Chronic Pain (pp. 43-58). New York: The Haworth
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Gold, D. T. (1994). Chronic Musculoskeletal Pain: Older Women and Their Coping Strategies.
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process and outcomes in stroke rehabilitation. Medical Care 40:1036-1047.
Hoenig H, Pieper C, Zolkewitz M, Schenkman M, Branch L (2002) Wheelchair users are not
necessarily wheelchair bound. Journal of the American Geriatrics Society 50:645-654.
Ingram S, Seo P, Martell R, Clipp E, Doyle M, Montana G, Cohen H (2002) Comprehensive
assessment of the elderly cancer patient: the feasibility of self-report methodology. Journal of
Clinical Oncology 20:770-775.
Kraus V, Huebner J, Fink C, King J, Brown S, TP V, Guilak F (2002) Urea as a passive transport
marker for arthritis biomarker studies. Arthritis & Rheumatology 46:420-427.
Kuchibhatla M, Fillenbaum G. (2002) Assessing risk factors for mortality in elderly Whites and
African American: implications of alternative analyses. The Gerontologist. 42(6):826-834.
Li Y, Scott W, Hedges D, Zhang F, Gaskell P, Nance M, Watts R, Hubble J, Koller W, Pahwa R,
Stern M, Hiner B, Jankovic J, Allen F, Goetz C, Mastaglia F, Stajich J, Gibson R, Middleton L,
Saunders A, Scott B, Small G, Nicodemus K, Reed A, Schmechel D, Welsh-Bohmer K,
Conneally P, Roses A, Gilbert J, Vance J, Haines J, Pericak-Vance M (2002) Age-at-onset in two
common neurodegenerative diseases is genetically controlled. American Journal of Human
Genetics 70:985-993.
Lyles K, Colon-Emeric C (2002) Can we identify women at high risk for osteoporotic fractures.
Journal of the American Geriatrics Society 50:1161-1162.
Lyles K (2002) Oncogenic Osteomalacia. In: JP Bilizekin LR, GA Rosen (ed) Principles on
Bone Biology. Academic Press, San Diego, CA.
Meyers A, Anderson J, Miller D, Shipp K, Hoenig H (2002) Barriers, facilitators, and access for
wheelchair users: substantive and methodologic lessons from a pilot study of environmental
effects. Social Science and Medicine 55:1435-1446.
Morey M, Pieper C, Crowley G, Sullivan R, Puglisi C (2002) Exercise adherence and ten year
mortality in chronically ill older adults. Journal of the American Geriatrics Society 50:19291933.
Pan D, Zhe X, Jakkaraju S, Taylor G, Schuger S (2002) P311 induces a TGF-ß-independent,
nonfibrogenic myofibroblast phenotype. Journal of Clinical Investigation 110:1349-1358.
Reker D, Duncan P, Horner R, Hoenig H, Samsa G, Hamilton B, Dudley T (2002) Post-acute
stroke guideline compliance leads to greater patient satisfaction. Archives of Physical Medicine
and Rehabilitation 83:750-756.
Reker D, Rosen A, Hoenig H, Laughlin A, Anderson L, Berlowitz D, Marshall C, Rittman R
(2002) The hazards of stroke case selection using administrative data. Medical Care 40:96-104.
Schmidt S, Klaver C, Saunders A, Postel E, De La Paz M, Agarwal A, Small K, Udar N, Ong J,
Chalukya M, Nesburn A, Kenny C, Domurath R, Hogan M, Mah T, Conley Y, Ferrell R, Weeks
D, de Jong P, van Duijn C, Haines J, Perocak-Vance M, Gorin M (2002) A pooled case-control
study of the apolipoprotein E (APOE) gene in age-related maculopathy. Opthalmic Genetics
23:209-233.
Van Staa T, Selby P, Leufkens H, Lyles K, Pieper C, Sprafka J, Cooper C (2002) Incidence and
natural history of Paget's disease of bone. Journal of Bone and Mineral Research 17:465-471.
Vilim V, Olejarova M, Machasek S, Gatterova J, Kraus V, Pavelka K (2002) Serum levels of
cartilage oligomeric matrix protein (COMP) correlate with radiographic progression of knee
osteoarthritis. Osteoarthritis and Cartilage 10:707-713.
Wilson C, Cohen H, Fillenbaum G, Pieper C (2002) Cytokines and cognition: the case for a head
to toe inflammatory paradigm. Journal of the American Geriatrics Society 50:2041-2056.
2003
Cohen H, Harris T, Pieper C (2003) Coagulation and inflammatory pathway activation in the
development of frailty and mortality. American Journal of Medicine 21:180-187.
Colón-Emeric C, Biggs D, Schenck A, Lyles K (2003) Risk factors for hip fractures in skilled
nursing facilities: Who should be treated? Osteoporosis International 14:484-489.
Colon-Emeric C, Datta S, Matchar D (2003) An economic analysis of external hip protector use
in ambulatory nursing home residents. Age and Aging 32:47-52.
Demark-Wahnfried W, Morey M, Clipp E, Pieper C, Snyder D, Sloane R, Cohen H (2003)
Leading the way in exercise and diet (Project LEAD): Intervention to improve function among
older breast and cancer survivors. Journal of Controlled Clinical Trials 24:206-223.
Demark-Wahnefried W and Rock CL. Nutrition-related issues for the breast cancer survivor.
Seminars in Oncology 30: 789-98, 2003.
Garman K, Pieper C, Seo P, Cohen H (2003) Function in elderly cancer survivors depends on
comorbidities. Journal of Gerontology: Medical Science 58:1119-1124.
Gold D (2003) Osteoporosis and quality of life: Psychosocial outcomes and interventions for
individual patients. Clinics in Geriatric Medicine 19:271-280.
Hoenig H, Landerman L, Shipp K, George L (2003) Activity restriction among wheelchair users.
Journal of the American Geriatrics Society 51:1244-1251.
Hoenig H, Taylor D, Sloan F (2003) Does assistive technology substitute for personal assistance
among the disabled elderly? American Journal of Public Health 93:330-337.
Jordan J, Luta G, Stabler T, Renner J, Dragomir A, Vilim V, Hochberg M, Helmick C, Kraus V.
(2003) Ethnic and gender differences in serum cartilage oligomeric matrix protein protein: the
Johnston County Osteoarthritis Project. Arthritis & Rheumatism 48:675-681.
Kingsmore S, Patel D (2003) Multiplexed protein profiling on antibody-based microarrays by
rolling circle amplification. Current Opinion in Biotechnology 14:74-81.
Kraus VB, Stabler T, Le ET, Saltarelli M, Allen NB (2003) Urinary type II collagen neoepitope
as an outcome measure for relapsing polychondritis. Arthritis & Rheumatism. 48:2942-2948.
Morey M, Dubbert P, Doyle M, MacAller H, Crowley G, Kuchibhatla M, Schenkman M, Horner
R (2003) From supervised to unsupervised exercise: factors associated with exercise adherence.
Journal of Aging and Physical Activity 11:351-368.
Morey M, Zhu C (2003) Improved fitness narrows the symptom-reporting gap between older
men and women. Journal of Women's Health and Gender-Based Medicine 12:381-390.
Morey MC, Sullivan J, Robert J. (2003) Medical assessment for health advocacy and practical
strategies for exercise initiation. American Journal of Preventive Medicine 25:204-208.
Peterson M, Pieper C, Morey M (2003) Accuracy of VO2max prediction equations in older
adults. Medicine and Science in Sports and Exercise 35:145-149.
Purser J, Pieper C, Poole C, Morey M (2003) Trajectories of leg strength and gait speed among
sedentary older adults: longitudinal pattern of dose response. Journal of Gerontology: Medical
Science 58A:1125-1134.
Schmidt S, Postel E, Agarwal A, Allen I, Jr., Walters S, De La Paz M, Scott W, Haines J,
Pericak Vance M, Gilbert J (2003) Detailed analysis of allelic variation in the ABCA4 gene in
age-related maculopathy. Investigative Opthalmology and Visual Sciences 44:2868-2875.
Scott W, Hauser E, Schmechel D, Welsh-Bohmer K, Small G, Roses A, Saunders A, Gilbert J,
Vance J, Haines J, Pericak-Vance M (2003) Ordered-subsets linkage analysis detects novel
Alzheimer disease Loci on chromosomes 2q34 and 15q22. American Journal of Human Genetics
73:1041-1051.
Sutton LM, Demark-Wahnefried W, Clipp EC (2003) Management of terminal cancer in elderly
patients. Lancet Oncology. 4:149-157.
Vilim V, Vobsrka Z, Vytasek R, Senolt L, Tchetverikov I, Kraus V, Pavelka K (2003)
Monoclonal antibodies to human cartilage oligomeric matrix protein (COMP): epitope mapping
and characterization of sandwich ELISA. Clinica Chimica Acta 328:59-69.
Wilson C, Cohen H, Pieper C (2003) Cross-linked fibrin degradation products (d-dimer), plasma
cytokines, and cognitive decline in community-dwelling elderly persons. Journal of the
American Geriatrics Society 51:1119-1124.
2004
Demark-Wahnefried W. (2004) Diet and the Prostate Cancer Survivor. Family Urology 9(3): 4.
Demark-Wahnefried W, Clipp EC, Morey M, Pieper C, Sloane R, Snyder DC, Cohen HJ.
Physical Function among Elders with Breast or Prostate Cancer: Associations with Diet and
Exercise. International Journal of Behavior in Nutrition and Physical Activity 1:16, 2004
(www.ijbnpa.org/content/1/1/16).
Garman KS, McConnell ES, and Cohen HJ (2004). Inpatient Care for Elderly Cancer
Patients: The Role for Geriatric Evaluation and Management Units in Fulfilling Goals for Care.
Critical Reviews in Oncology Hematology 51(3):241-247.
Gold, D.T., Shipp, K.M., Pieper, C.F., Purser, J.L., Duncan, P.W., Martinez, S., & Lyles, K.W.
(2004) Group treatment improves trunk strength and psychological status in older women with
vertebral fractures: Results of a randomized clinical trial. Journal of the American Geriatrics
Society, 52, 1471-1478.
Hoenig H, Siebens H. (2004). A research agenda for geriatric rehabilitation. American Journal of
Physical Medicine and Rehabilitation. 83(11):858-66.
Peterson MJ, Morey MC, Crowley GM, Sullivan RJ. (2004) Physical function in sedentary and
exercising older veterans compared to national norms. Journal of Rehabilitation Research and
Development. 41(5):653-658.
Roberto, K.A., Gold, D.T., & Yorgasson, J. (2004). The influence of osteoporosis on the marital
relationship of older couples. Journal of Applied Gerontology, 23, 443-456.
Seo PH, Pieper CF, and Cohen HJ (2004). Effects of Cancer History and Comorbid Conditions
on Mortality and Healthcare Utilization among Older Cancer Survivors. Cancer 101:10:227684.
Stabler, TS, J-C Piette, X Chevalier, A Marini and VB Kraus (2004). Serum cytokine profiles in
relapsing polychondritis suggest monocyte/macrophage activation. Arthritis Rheum
50(11):3663- 3667.
Stookey JD, Pieper CF, Cohen HJ.(2004) Hypertonic hyperglycemia progresses to diabetes
faster than normotonic hyperglycemia. European Journal of Epidemiology. 19(10):935-44.
Stookey JD, Purser JL, Pieper CF, and Cohen HJ (2004). Plasma Hypertonicity: Another Marker
of Frailty? Journal of the American Geriatrics Society 52:1313-1320.
Taylor D, Hoenig H (2004) The effect of equipment usage and residual task difficulty on use of
personal assistance, days in bed and nursing home placement. Journal of the American
Geriatrics Society 52:72-79.
Warner G, Hoenig H, Montez M, Wang F, Rosen A (2004). Evaluating diagnosis-based riskadjustment methods in the spinal cord dysfunction population. Archives of Physical Medicine
and Rehabilitation. 85:218-226.
Zinn S, Dudley T, Hoenig H, Bosworth J, Reker D, Hamilton B, Duncan P, Horner R The effect
of post-stroke cognitive impairment on rehabilitation process and functional outcome. Archives
of Physical Medicine and Rehabilitation, 2004; vol. 85 1084-1090.
2005
Ashley-Koch AE, Shao Y, Rimmler JB, Gaskell PC, Welsh-Bohmer KA, Jackson CE, Scott
WK, Haines JL, Pericak-Vance MA. An autosomal genomic screen for dementia in an extended
Amish family. Neurosci Lett. 2005 May 13;379(3):199-204.
Criscione, LG, AL Elliott, TV Stabler, JM Jordan, CF Pieper, VB Kraus. Variation of Serum
Hyaluronan with Activity in Individuals with Knee Osteoarthritis. Osteo & Cartilage.2005: 13,
837-40.
Demark-Wahnefried W, Aziz N, Rowland J, Pinto BM. Riding the Crest of the Teachable
Moment: Promoting Long-Term Health After the Diagnosis of Cancer. Journal of Clinical
Oncology, Aug. 20 2005, 5814-5830.
Fisher SA, Abecasis GR, Yashar BM, Zareparsi S, Swaroop A, Iyengar SK, Klein BE, Klein R,
Lee KE, Majewski J, Schultz DW, Klein ML, Seddon JM, Santangelo SL, Weeks DE, Conley
YP, Mah TS, Schmidt S, Haines JL, Pericak-Vance MA, Gorin MB, Schulz HL, Pardi F, Lewis
CM, Weber BH. Meta-analysis of genome scans of age-related macular degeneration. Hum Mol
Genet. 2005 Aug 1;14(15):2257-64. Epub 2005 Jun 29
Haines JL, Hauser MA, Schmidt S, Scott WK, Olson LM, Gallins P, Spencer KL, Kwan SY,
Noureddine N, Gilbert JR, Schnetz-Boutaud, N, Agarwal, A, Postel EA, Pericak-Vance, MA
(2005). Complement Factor H Variant Increases the Risk of Age-Related Macular Degeneration.
Science 308:419-421.
Hoenig, H, Landerman, HR, Shipp, KM, Pieper,C, Pieper,C, Richardson,M, Pahel, N, George,L,
‘A Clinical Trial of a Rehabilitation Expert Clinician Versus Usual Care for Providing Manual
Wheelchairs.’ Journal of the American Geriatrics Society, 2005: 53, 1712-1720.
Ingram S, Seo P, Sloane R, Francis T, Clipp E, Doyle M, Montana G, Cohen H (2005) The
association of oral health with general health and quality of life in older cancer patients. JAGS
53:1504-1509.
Kraus, V, A Elliot, G Luta, T Stabler, JB Renner, AD Dragomir, CG Helmick, MC Hochberg
and JM Jordan. (2005). Serum hyaluronan levels and radiographic knee osteoarthritis in African
Americans and Caucasians in the Johnston County Osteoarthritis Project. Arthritis Rheum
52(1):105-111.
Kuchibhatla M, Fillenbaum G. G. Modeling Association in Longitudinal Binary Outcomes: A
Brief Review. Aging and Mental Health. May 2005; 9(3): 196-200.
Piscoya JL, B Fermor, VB Kraus, TV Stabler, and F Guilak. 2005. The dose response
relationship of mechanical compression on the induction of osteoarthritis-related biomarkers in
articular cartilage explants. Osteo & Cartilage 13(12): 1092-9.
Purser, JL, Fillenbaum,GG, Pieper,CF, Wallace, RB, ‘Mild Cognitive Impairment and Ten-Year
Trajectories of Disability in the Iowa EPESE Cohort’, Journal of the American Geriatrics
Society, 2005: 53, 1966-1972.
Purser JL, Weinberger M, Cohen HJ, Pieper CF, Morey MC, Li T, Williams GR, Lapuerta P.
(2005) Walking speed predicts health status and hospital costs for frail elderly veterans. Journal
of Rehabilitation Research and Development. 42:4:535
Schmidt S, Haines JL, Postel EA, Agarwal A, Kwan SY, Gilbert JR, Pericak-Vance MA, Scott
WK. Joint effects of smoking history and APOE genotypes in age-related macular degeneration.
Mol Vis. 2005 Nov 4;11:941-9.
Stansbury JP, Jia H, Williams LS, Vogel WB, Duncan PW. Ethnic disparities in stroke:
Epidemiology, acute care, and post-acute outcomes. Stroke. 2005;36:374-386.
Stookey, J, Pieper, CF, Cohen, HJ, ‘Is the prevalence of dehydration among community-dwelling
older adults really low?: Informing current debate over the fluid recommendation for 70+ adults’
Public Health Nutrition, 2005: 8 (8), 1275-1285
van der Walt JM, Scott WK, Slifer S, Gaskell PC, Martin ER, Welsh-Bohmer K, Creason M,
Crunk A, Fuzzell D, McFarland L, Kroner CC, Jackson CE, Haines JL, Pericak-Vance MA.
Maternal lineages and Alzheimer disease risk in the Old Order Amish. Hum Genet. 2005
Oct;118(1):115-22. Epub 2005 Oct 28.
2006
Cohen A, Pieper C, Brown A, Bastian LA, ‘Number of children and the risk of metabolic
syndrome in women’, Journal of Women’s Health, accepted March 2006.
Demark-Wahnefried W, Clipp EC, Morey MC, Pieper CF, Sloane R, Snyder DC, Cohen HJ.A
Lifestyle Intervention Development Study to Improve Physical Function in Older Adults with
Cancer: Outcomes from Project LEAD (Leading the Way in Exercise And Diet). Journal of
Clinical Oncology 24:3465-3473. (2006)
Dominick K and Morey MC. Adherence to Physical Activity in Patient Treatment Adherence:
Concepts, Interventions and Measurement. Lawrence Erlbaum Associates, Inc., Mahwah, NJ.
Editors: Bosworth, HB, Oddone, EZ, Weinberger, M.; Physical Function / Exercise and
Adherence, (2006).
Fillenbaum, G.G., Hybels, C.F., Pieper, C.F., Konrad, T.R., Burchett, B.M., Blazer, D.G.
Provider characteristics related to antidepressant use in the elderly. Journal of the American
Geriatrics Society, 2006, 54, 942-949.
Fillenbaum, G.G. & Hanlon, J.T. Racial and ethnic disparities in medication utilization in older
adults. (editorial) American Journal of Geriatric Pharmacotherapy, 2006, 4, 93-95.
Jia H, Zheng YE, Cowper DC, Stansbury JP, Wu SS, Vogel WB, Duncan PW, Reker DM.
Race/ethnicity: Who is counting what? J Rehabil Res Dev. 2006 Jul-Aug;43(4):475-84.
Hahs DW, McCauley JL, Crunk AE, McFarland LL, Gaskell PC, Jiang L, Slifer SH, Vance JM,
Scott WK, Welsh-Bohmer KA, Johnson SR, Jackson CE, Pericak-Vance MA, Haines JL. A
genome-wide linkage analysis of dementia in the Amish. Am J Med Genet B Neuropsychiatr
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Haines JL, Schnetz-Boutaud N, Schmidt S, Scott WK, Agarwal A, Postel EA, Olson L, Kenealy
SJ, Hauser M, Gilbert JR, Pericak-Vance MA. Functional candidate genes in age-related
macular degeneration: significant association with VEGF, VLDLR, and LRP6. Invest
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Hedayati, SS, Bosworth, HB. Kuchibhatla M., Kimmel, PL, Szczech, LA. (2006) ’The predictive
value of self-report scales compared with physician diagnosis of depression in hemodialysis
patients’. Kidney Int. 1662-1668.
Heflin, MT, Pollak KI, Kuchibhatla M, Branch LG, Oddone EZ, M. The impact of health status
on physicians' intentions to offer cancer screening to older women. J Gerontology Medical
Sciences. J Gerontol A Biol Sci Med Sci 2006 61: 844-850.
Hoenig H, Ganesh S, Taylor DH, Pieper C, Guralnik J, Fried L. Lower extremity physical
performance and use of compensatory strategies for mobility. Journal of the American Geriatrics
Society, 2006: 54(2), 262-269.
Huffman KM, Samsa GP, Slentz CA, Duscha BD, Johnson JL, Bales CW, Tanner CJ, Houmard
JA, and Kraus WE: Response of High Sensitivity C-Reactive Protein to Exercise Training in an
At-Risk Population. American Heart Journal. 152(4): 793-800, 2006.
Huffman KM, Bowers JR, Dailiana Z, Huebner JL, Urbaniak JR, Kraus VB: Synovial Fluid
Metabolites in Osteonecrosis. Rheumatology (Oxford). 46(3): 523-8, 2006.
Kraus VB, and JM Jordan. 2006. Serum C-Reactive Protein (CRP), target for therapy or marker
for trouble? Biomarker Insights 2:1-4 (http://www.la-press.com/biomark.htm).
Kraus VB, T Stabler, G Luta, JB Renner, AD Dragomir and JM Mordan. 2006. Interpretation of
serum C-reactive protein (CRP) levels for cardiovascular disease risk is complicated by race,
gender, body mass index and pulmonary disease. Osteoarthritis Cartilage. E-pub ahead of print
Kraus VB, Jordan JM. 2006. Serum C-Reactive Protein (CRP), target for therapy or marker for
trouble? Biomarker Insights.
McCauley JL, Hahs DW, Jiang L, Scott WK, Welsh-Bohmer KA, Jackson CE, Vance JM,
Pericak-Vance MA, Haines JL. Combinatorial Mismatch Scan (CMS) for loci associated with
dementia in the Amish. BMC Med Genet. 2006 Mar 3;7:19.
Morey MC, Ekelund CC, Pearson MP, Crowley GM, Peterson MJ, Sloane R, Pieper CF,
McConnell E, Bosworth H, Chapman JP. Project LIFE: A partnership to improve physical
activity in elders with multiple chronic illnesses, Journal of Aging and Physical Activity, 2006,
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Purser JL, Fillenbaum GG, Wallace RB: Memory Complaint Is Not Necessary for Diagnosis of
MCI and Does Not Predict 10-year Trajectories of Functional Disability, Word Recall or
SPMSQ Limitations. J Am Geriatr Soc, 2006; 54:335-338
Purser JL, Kuchibhatla MN, Fillenbaum GG, Harding T, Peterson ED, Alexander KP:
Identifying Frailty Among Hospitalized Older Adults with Significant Coronary Artery Disease.
J Am Geriatr Soc, 2006; 54:1674-1681
Rao AV, Demark-Wahnefried W. The older cancer survivor. Critical Reviews in
Oncology/Hematology 60:131-143, 2006
Schmidt S, Hauser MA, Scott WK, Postel EA, Agarwal A, Gallins P, Wong F, Chen YS,
Spencer K, Schnetz-Boutaud N, Haines JL, Pericak-Vance MA. Cigarette smoking strongly
modifies the association of LOC387715 and age-related macular degeneration. Am J Hum Genet.
2006 May; 78(5):852-64. Epub 2006 Mar 20.
Xu PT, Li YJ, Qin XJ, Scherzer CR, Xu H, Schmechel DE, Hulette CM, Ervin J, Gullans SR,
Haines J, Pericak-Vance MA, Gilbert JR. Differences in apolipoprotein E3/3 and E4/4 allelespecific gene expression in hippocampus in Alzheimer disease. Neurobiol Dis. 2006
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2007
Blay SL, Andreoli SB, Fillenbaum GG, Gastal FL. Depression morbidity in later life:
prevalence and correlates in a developing country. Am J Geriatr Psychiatry 2007 Sep;
15(9):790-799.
Cavanaugh J, Coleman K, Gaines J, Morey M. Variability of stepping activity and number of
activity bouts distinguish healthy older adults from younger adults. (2007) Journal of the
American Geriatrics Society, 55(1):120-124.
Fillenbaum, G.G., Kuchibhatla, M., Henderson, V.W., Clark, C.M., Taussig, I.M. Comparison of
performance on the CERAD Neuropsychological Battery of Hispanic patients and cognitively
normal controls at two sites. Clinical Gerontologist, 2007, 30(3), 1-22. DOI:10.1300
Ganesh S, Hayter A, Kim J, Sanford J, Sprigle S, Hoenig H. Wheelchair use by veterans newly
prescribed a manual wheelchair. Arch Phys Med Rehabil 2007; 88(4):434-439.
Hastings SN, Whitson HE, McConnell ES, Lekan-Rutledge DA, Sloane R, MacDonald H, White
H. Development and Implementation of the TrAC (Tracking After-hours Calls) Database: A
Tool to Collect Longitudinal Data on After-Hours Telephone Calls in Long-Term Care Journal
of the American Medical Directors Association 2007 March 8(3):178-82.
Hoenig H, Pieper C, Branch LG, Cohen HJ. Effect of motorized scooters on physical
performance and mobility: a randomized clinical trial. Arch Phys Med Rehabil 2007; 88(3):279286.
Huebner JL, DR Seifer and VB Kraus. 2007. A longitudinal analysis of serum cytokines in the
Hartley guinea pig model of osteoarthritis. Osteoarthritis Cartilage 15: 354-356.
Monetti M, Levin MC, Watt MJ, Sajan MP, Marmor S, Hubbard BK, Stevens RD, Bain JR,
Newgard CB, Farese RV Sr, Hevener AL, and Farese RV Jr. Dissociation of Hepatic Steatosis
and Insulin Resistance in Mice Overexpressing DGAT in the Liver. Cell Metab. Jul
2007;6(1):69-78. PMID: 17618857 doi:10.1016/j.cmet.2007.05.005
Purser JL, Fillenbaum GG, Alexander KP. Response to Dr. Denkinger et al. Journal of the
American Geriatrics Society, 55:968-969, 2007.
Richards JB, Papaiouannou A, Adachi JD, Joseph L, Whitson HE, Prior JC, Goltzman D: The
impact of selective serotonin reuptake inhibitors on the risk of fracture. Archives of Internal
Medicine. 2007 Jan 167(2): 188-94.
Schiffman SS, Sattely-Miller EA, Taylor EL, Graham BG, Landerman LR, Zervakis J,
Campagna LK, Cohen HJ, Blackwell S, Garst JL. Combination of flavor enhancement and
chemosensory education improves nutritional status in older cancer patients. Journal of
Nutrition, Health and Aging, 2007; vol. 11 pp 439-454.
Stull VB, Snyder DC, Demark-Wahnefried W. Lifestyle Interventions in Cancer Survivors:
Designing Programs that Meet the Needs of this Vulnerable and Growing Population. Journal of
Nutrition 137: 243S-248S, 2007
Walker VA, Whitson HE: Smoking cessation in older adults: a review. Geriatrics and Aging
2007 (Published 2007).
Whitson HE, Cousins SW, Burchett BM, Hybels CF, Pieper CF, Cohen HJ. The combined
effect of visual impairment and cognitive impairment on disability in older people. J Am
Geriatri Soc 2007 Jun; 55(6): 885-91.
Whitson HE, Purser JL, Cohen HJ. Frailty thy name is…phrailty? J of Gerontol A Biol Sci Med
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2008
Blay SL, Fillenbaum GG, Andreoli SB, Gastal FL. Equity of access to outpatient care and
hospitalization among older community residents in Brazil. Medical Care 2008 Sept; 46(9),
930-937.
Brummett BH, Boyle SH, Siegler IC, Kuhn CM, Surwit RS, Garrett ME, Collins A, Ashley
Koch A, Williams RB. HPA axis function in male caregivers: effect of the monoamine oxidasea gene promoter (MAOA-uVNTR). Biol Psychol 2008 Oct; 79(2):250-255. PMCID:
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Carney RM, Slifer MA, Lin PI, Gaskell PC, Scott WK, Potocky CF, Hulette CM, WelshBohmer KA, Schmechel DE, Vance JM, Pericak-Vance MA. Longitudinal follow-up of lateonset Alzheimer disease families. Am J Med Genet B Neuropsychiatr Genet. 2008 Mar 24
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Chen HC, Shah S, Stabler TV, Li Y-J, and Kraus VB. Biomarkers associated with clinical
phenotypes of hand osteoarthritis in a large multigenerational family: the CARRIAGE Family
study. Osteo Cartilage 2008, PMID: 18291686 doi:10.1016/j.joca.2007.12.010
Chen H-C, Shah SH, Li YJ, Stabler TV, Jordan JM, and Kraus VB. Inverse association of
general joint hypermobility with hand and knee osteoarthritis and serum cartilage oligomeric
matrix protein levels. Arthritis & Rheumatism 2008;58(12):3854-64. PMCID: PMC – in process
Demark-Wahnefried W and Aziz N. Health promotion and disease prevention among adult
survivors. In SM Miller, DJ Bowen, RT Croyle and J Rowland (eds). Handbook of Behavioral
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Fillenbaum, G.G. Differential survival with Alzheimer disease. (Editorial) Neurology, 2008, 70,
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Fillenbaum GG, van Belle G, Morris JC, Mohs RC, Mirra SS, Davis PC, Tariot PN, Silverman
JM, Clark CM, Welsh-Bohmer KA, Heyman A. Consortium to Establish a Registry for
Alzheimer’s Disease (CERAD): the first twenty years. Alzheimers Dement 2008 Mar; 4(2):96109. PMCID: PMC2808763
Hastings SN, Purser JL, Johnson KS, Sloane RJ, Whitson HE. Frailty predicts some but not all
adverse outcomes in older adults discharged from the emergency department. J Am Geriatri Soc
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Hastings SN, Whitson HE, White HK, Sloane R, MacDonald H, Lekan DA, McConnell ES.
After-Hours Calls from Long-Term Care Facilities in a Geriatric Medicine Training Program.
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Huffman KM, Slentz CA, Johnson JL, Samsa GP, Duscha BD, Tanner CJ, Annex BH, Houmard
JA, and Kraus WE. Impact of Hormone Replacement Therapy on Exercise Training-Induced
Improvements in Insulin Action in Sedentary Overweight Adults. Metabolism-Clinical and
Experimental 2008;57(7):888-85. PMCID: PMC2518063
Huffman KM, Slentz CA, Bales CW, Houmard JA, and Kraus WE. Relationships between
Adipose Tissue and Cytokine Responses to a Randomized Controlled Exercise Training
Intervention. Metabolism-Clinical and Experimental, 57(4): 577-83, 2008. PMID: 18328363
doi:10.1016/j.metabol.2007.11.023
Huffman KM, Orenduff MC, Samsa GP, Houmard JA, Kraus WE, and Bales CW. Dietary
carbohydrate intake and high sensitivity C reactive protein in at-risk women and men. American
Heart Journal, 154(5):962-8, 2007. PMID: 17967604 doi:10.1016/j.ahj.2007.07.009
Morey MC, Peterson MJ, Pieper CF, Sloane R, Crowley GM, Cowper P, McConnell E,
Bosworth H, Ekelund C, Pearson M, Howard T. Project LIFE—Learning to Improve Fitness and
Function in Elders: methods, design, and baseline characteristics of randomized trial. J Rehabil
Res Dev 2008; 45(1):31-42.
Morey MC, Sloane R, Pieper CF, Peterson MJ, Pearson MP, Ekelund CC, Crowley GM,
Demark-Wahnefried W, Snyder DC, Clipp EC, Cohen HJ. Effect of physical activity guidelines
on physical function in older adults. J Am Geriatr Soc 2008 Oct; 56(10):1873-1878. PMCID:
NIHMSID113377
Peterson BL, Fillenbaum GG, Pieper CF, Heyman A. Home or nursing home: does place of
residence affect longevity in patients with Alzheimer’s disease? Public Health Nursing 2008;
25(5):490-497.
Purser JL, Kuchibhatla MN, Cohen HJ, Blazer DG, Miranda ML, Fillenbaum GG.
Geographical segregation and interleukin-6, a biomarker of chronic inflammation in older adults.
Biomarkers in Medicine 2008; 2(4):335-348. PMCID: NIHMSID97930
Singh M, Alexander K, Roger VL, Rihal CS, Whitson HE, Lerman A, Jahangir A, Nair KS.
Frailty and its potential relevance to cardiovascular care. Mayo Clinical Proceedings 2008 Oct;
83(10):1146-1153. PMCID: PMC2704096
Whitson HE Pieper CF, Cohen HJ New Light on an Age-old issue Mechanisms of Ageing and
Development. 2008 Nov;129(11):673-674 PMCID: PMC2628446
Whitson HE, Sanders L, Pieper CF, Gold DT, Papaioannou A, Richards JB, Adachi JD, Lyles
KW and the CaMos Research Group. Depressive symptomatology and fracture risk in
community-dwelling older men and women. Aging Clin and Exp Res 2008 Dec; 20(6) 585-92.
Whitson HE, Hastings SN, Lekan DA, Sloane R, White HK, McConnell ES. A quality
improvement program to enhance after-hours telephone communication between nurses and
physicians in a long-term care facility. J Am Geriatri Soc 2008; 56(6):1080-6.
Xiao X, Zhang ZX, Cohen HJ, Wang H, Li W, Wang T, Xu T, Liu A, Gai MY, Ying S, Schmitz
O, Yi Z. Evidence of a relationship between infant birth weight and later diabetes and impaired
glucose regulation in a Chinese population. Diabetes Care 2008 Mar; 31(3):483-487.
2009
Bain JR, Stevens RD, Wenner BR, Ilkayeva O, Muoio DM, Newgard CB. Metabolomics
applied to diabetes research: moving from information to knowledge. Diabetes 2009 Nov;
58(11):2429-2443. PMC2768174.
Blay SL, Fillenbaum GG, Andreoli SB, Gastal FL. Correlates of and relationship among lifetime
alcohol abuse and alcohol dependence in older community residents in Brazil. Int Psychiatry
2009; 6(2):40-44. PMC2686381
Brummett BH, Mark D, Fillenbaum GG, Morey M. Prospective study of associations among
positive emotion and physical function in older patients with coronary artery disease. Journal of
Gerontology: Psychological Sciences 2009 64B(4-June), 461-469. PMC2697502.
Catterall*, J, D Barr*, M Bolognesi, RD Zura and VB Kraus. 2009. Post-translational aging of
proteins in osteoarthritic cartilage and synovial fluid as measured by isomerized aspartate.
Arthritis Res Ther 11(2):R55. (*contributed equally to this work) PMC2688206.
Cibere, H, H Zhang, P Garnero, AR Poole, T Lobanok, T Saxne, VB Kraus, A Way, A Thorne,
H Wong, J Singer, J Kopec, A Guermazi, C Peterfy, S Nicolaou, PL Munk and JM Esdaile.
2009. Association of biomarkers with pre-radiographically defined and radiographically defined
knee osteoarthritis in a population-based study. Arthritis Rheum, 60:1372-80. PMID:
19404937.
Demark-Wahnefried W, Morey MC, Sloane R, Snyder DC, Cohen HJ. Promoting healthy
lifestyles among older cancer survivors to improve health and preserve function. JAGS 2009
Supplement 2 S262-4. PMC in process
Fillenbaum, G.G., Burchett, B.M., & Blazer, D.G. Identifying a National Death Index match.
American Journal of Epidemiology, 2009, 170, 515-518. PMC2727178.
Hastings SN, Whitson HE, Purser J, Sloane RI, Johnson KS. Emergency department discharge
diagnosis and adverse health outcomes in older adults Journal of the American Geriatrics
Society. 2009 Oct;57(10):1856-61, PMC2866093.
Huffman, KM, SH Shah, RD Stevens, JR Bain, M Muehlbauer, CA Slentz, CJ Tanner, M
Kuchibhatla, JA Houmard, CB Newgard. Relationships between circulating metabolic
intermediates and insulin action in overweight to obese, inactive men and women. Diabetes
Care. 2009 Sept 32(9):1678-1683. PMC2732163.
Hybels CF, Pieper CF, Blazer DG. The complex relationship between depressive symptoms and
functional limitations in community-dwelling older adults: the impact of sub-threshold
depression. Psychol Med 2009 Oct 3 9(10):1677-1688. PMC2741540.
Hybels, C.F., Pieper, C.F., Blazer, D.G., Fillenbaum, G.G., & Steffens, D.C. Trajectories of
mobility and IADL function in older patients diagnosed with major depression. International
Journal of Geriatric Psychiatry, 2010, 25(1), 74-81. PMC2894462 DOI: 10/1002/gps.2300.
Hybels CF, Blazer DG, Pieper CF, Landerman LR, Steffens DC, Profiles of Depressive
Symptoms in Older Adults Diagnosed with Major Depression: A Latent Cluster Analysis Am J
Geriatr Psychiatry. Author manuscript; available in PMC 2010 May 1. Published in final edited
form as: Am J Geriatr Psychiatry. 2009 May; 17(5): 387–396.
doi: 10.1097/JGP.0b013e31819431ff PMCID: PMC2718569
Hybels CF & Pieper CF. ‘Epidemiology and geriatric psychiatry.’, Editorial. American Journal
of Geriatric Psychiatry, 2009: 17(8), 627-631.
Johnson KS, Kuchibhatla M, Tulsky JA. Racial differences in self-reported exposure to
information about hospice care. J Palliat Med 2009;12: 921-927. PMC2904186
Kraus VB, McDaniel G, Worrell TW, Feng S, Vail TP, Varju G, Coleman RE. Association of
bone scintigraphic abnormalities with knee malalignment and pain. Ann Rheum Dis 2009 Nov;
68(11):1673-1679. PMID: 18981032
Makowski L, Noland RC, Koves TR, Xing W, Ilkayeva OR, Muehlbauer MJ, Stevens RD,
Muoio DM. Metabolic profiling of PPARalpha-/- mice reveals defects in carnitine and amino
acid homeostasis that are partially reversed by oral carnitine supplementation. FASEB J 2009
Feb; 23(2):586-604. PMCID: PMC2630792
Mercer VS, Freburger JK, Change SH, Purser JL. Step test scores are related to measures of
activity and participation in the first 6 months after stroke. Phys Ther 2009 Oct; 89(10):10611071. PMC2755462.
Morey MC, Peterson MP, Pieper CF, Sloane R, Crowley GM, Cowper PA, McConnell ES,
Bosworth HB, Ekelund CC, Pearson MP. The Veterans Learning to Improve Fitness and
Function in Elders study: A randomized trial of primary care based physical activity counseling
for older men. JAGS 57(7-July):1166-1174, 2009. PMC2757328.
Mosher CE, Sloane R, Morey MC, Snyder DC, Cohen HJ, Miller PE, Demark-Wahnefried W.
Associations between lifestyle factors and quality of life among older long-term breast, prostate,
and colorectal cancer survivors. Cancer 2009 Sep 1; 115(17):4001-4009. PMCID:
PMC2743037.
Morey MC, Snyder DC, V, Sloane R, Cohen HJ, Peterson B, Miller PE, Demark-Wahnefried
W. Effects of home-based diet and exercise on functional outcomes among older, overweight
long-term cancer survivors. JAMA 2009; 301(18-May):1883-1891. Selected as feature article
for the JAMA Report video. PMCID: PMC2752421.
Noland R, Koves TR, Seiler S, Lum H, Slentz DS, Ilkayeva O, Stevens R, Muoio DM. Carnitine
insufficiency caused by aging and overnutrition compromises mitochondrial performance and
metabolic control. J Biol Chem 2009 Aug 21; 284(34):22840-22852. PMC2755692.
Sloane R, Snyder DC, Demark-Wahnefried W, Lobach D, Kraus WE. Comparing the 7-day
physical activity recall with a triaxial accelerometer for measuring time in exercise. Med Sci
Sports Exerc 2009 June; 41(6):1334-1340. PMC2686118.
Snyder DC, Morey MC, Sloane R, Stull V, Cohen HJ, Peterson B, Pieper CF, Hartman TJ,
Miller PE, Mitchell DC, Demark-Wahnefried W. Reach out to ENhancE Wellness in older
cancer survivors (RENEW): design, methods and recruitment challenges of a home-based
exercise and diet intervention to improve physical function among long-term survivors of breast,
prostate, and colorectal cancer. Psycho-Oncology 2009 Apr; 18(4):429-439. PMC: 2748788
Stabler T, Byers S, Zura R, Kraus VB. Amino Acid Racemization Reveals Differential Protein
Turnover in Osteoarthritic Articular and Meniscal Cartilage. Arthritis Research Ther. 2009
11(2): R34. PMC2688179.
Stabler, TV, SS Byers, RD Zura and VB Kraus. 2009. Amino acid racemization reveals
differential protein turnover in osteoarthritic articular and meniscal cartilages. Arthritis Research
& Therapy 11(2):R34 (6 March 2009). PMC2688179
Whitson HE, Sanders L, Pieper CF, Morey M, EZ Oddone, DT Gold, HJ Cohen. Correlation of
Symptoms to Function in Older Adults with Comorbidity. Journal of the American Geriatrics
Society 2009 Apr;57(4):676-82, PMC2674624.
2010
Allen KD, Oddone EZ, Coffman CJ, Datta SK, Juntilla KA, Lindquist JH, Walker TA,
Weinberger M, BOSWORTH HB, Telephone-Based Self-Management of Osteoarthritis: A
Randomized, Controlled Trial. Annals of Internal Medicine. 2010 (In Press).
Allen JD, Stabler T, Kenjale A, Ham KL, Robbins JL, Duscha BD, Dobrosielski DA, Annex BH.
Plasma nitrate flux predicts exercise performance in peripheral arterial disease after 3 months of
exercsise training. Free Radic Biol Med 2010 Sep 15;49(6):1138-44. PMC2922965.
Brummett BH, Morey CM, Boyle SH, and Mark DB. Prospective study of associations among
positive emotion and functional status in patients with cardiac disease. J Gerontol B Psychol Sci
Soc Sci. 2009 Jun;64(4):461-9. Epub 2009 Jun 10. PMC2697502.
Brummett BH, Boyle SH, Kuhn CM, Siegler IC, Williams RB. Socioeconomic status moderates
associations between CNS serotonin and expression of beta2-integrins CD11b and CD11c. J
Psychiatr Res 2010 Apr; 44(6):373-377. PMC2849917.
Catterall*, J, D Barr*, M Bolognesi, RD Zura and VB Kraus. 2009. Post-translational aging of
proteins in osteoarthritic cartilage and synovial fluid as measured by isomerized aspartate.
Arthritis Res Ther 11(2):R55. (*contributed equally to this work) PMC2688206
Catterall, JB, TS Stabler, CR Flannery, and VB Kraus. 2010. Changes in serum and synovial
fluid biomarkers after acute injury. Arthritis Res & Therapy 12:R229. Epub 2010 Dec. 31.
PMID: 21194441. PMC3046542
Cavanaugh JT, Kochi N, Stergiou N. Nonlinear Analysis of Ambulatory Activity Patterns in
Community-Dwelling Older Adults. J Gerontol A Bio Sci Med Sci 2010 Feb; 65(2):197-203.
PMC2806237.
Cavanaugh JT, Kochi N, Stergiou N. Nonlinear Analysis of Ambulatory Activity Patterns in
Community-Dwelling Older Adults J Gerontol A Biol Sci Med Sci. 2010 February; 65A(2):
197–203. Published online 2009 October 12. doi: 10.1093/gerona/glp144
PMCID: PMC2806237
Chen HC, Kraus VB, Li YJ, Nelson S, Haynes C, Johnson J, Stabler T, Hauser E, Gregory G,
Kraus WE, Shah S. Genome-wide linkage analysis of quantitative biomarker traits of
osteoarthritis in a large multigenerational extended family. Arthritis Rheum. 2010 Mar;
62(3):781-90. PMCID: PMC - in process.
Chen TD, Anderson DJ, Chopra T, Choi Y, Schmader KE, Kaye KS. Poor Functional Status is
an Independent Predictor of Surgical Site Infections due to Methicillin-Resistant Staphylococcus
aureus in Older Adults. J Am Geriatric Soc 2010;58:527-532. PMC2892722
Cheng, W-M, TV Stabler, M Bolognesi and VB Kraus. 2010. Selenomethionine inhibits IL-1β
induced nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2) expression through the p38
MAPK pathway in primary human chondrocytes (in press).
Chumbler NR, Rose D. Griffiths P, Quigley P, McGee-Hernandez N, Carlson KA, Vandenberg
P, Morey M, Sanford J, Hoenig H. Home-based Telehealth Stroke Care: A Randomized Trial for
Veterans. Trials 2010, 11:74, PMC 2094744
Cohen HJ, Functional Assessment and the Cancer Survivor: Something Old, Something New, J
Natl Cancer Inst (2010) 102 (19): 1450-1451.
Denoble, A, N Hall, C Pieper and VB Kraus. 2010. Patellar skin surface temperature by
thermography reflects knee osteoarthritis. Clinical Medicine Insights: Arthritis and
Musculoskeletal Disorders 3:69-75. PMC2998980.
Fillenbaum GG, Blay SL, Andreoli SB. Prevalence and Correlates of Functional Status in an
Older Community-Representative Sample in Brazil. J Aging Health 2010 Apr; 22(3):362-383.
PMCID: PMC – in process
Fillenbaum, G.G., Kuchibhatla, M.N., Whitson, H.E., Batch, B.C., Svetkey, L.P., Pieper, C.F.,
Kraus, W.E., Cohen, H.J., & Blazer, D.G. Accuracy of self-reported height and weight in a
community-based sample of older African Americans and Whites. Journals of Gerontology: A
Biological Sciences Medical Sciences, 2010, 65A(10), 1123-1129. First published online June 7,
2010 doi:10.1093/gerona/glq096. PMC Journal – PMC2949332
Golightly, YM, SW Marshall, PhD, VB Kraus, A Villaveces, C Casteel, JM Jordan. 2010.
Biomarkers of incident radiographic knee osteoarthritis: Do they vary by lower extremity injury
history and chronic knee symptoms? Arthritis Rheum PMID:21506100
Jones LW, Eves ND, Spasojevic I, Wang F, Il’yasova D, Effects of Aerobic Training on
Oxidative Status in Postsurgical Non-Small Cell Lung Cancer Patients: A Pilot Study. Lunc
Cancer (2010), doi: 10-1016/j.lungcan.2010.08. PMID:20863590
Hall KS, Crowley GM, Bosworth HB, Howard TA, Morey MC.. Individual Progression toward
Self-Selected Health and Walking Goals among Older Adults Enrolled in a Physical Activity
Counseling Intervention. Journal of Aging and Physical Health 2010: Oct 18(4);439-450.
PMID:20956844
Hall KS, Crowley GM, McConnell ES, BOSWORTH HB, Sloane R, Ekelund CC, Morey MM.
(2010). Changes in goal ratings as a mediating variable between self-efficacy and physical
activity in older men. Annals of Behavioral Medicine. 39; 267-273. PMC2904848
Hastings SN, Horney C, Landerman LR, Sanders L, Hocker, M, Schmader KS. Exploring
patterns of health service use in older Emergency Department. Acad Emerg Med 2010.
PMID:21040110
Hayden,KM Jones,RN, Zimmer,C, Plassman,BL, Browndyke, JN, Pieper,CF, Warren, LH,
Welsh-Bohmer, KA, 'Factor Structure of the National Alzheimer’s Coordinating Centers
Uniform Dataset Neuropsychological Battery: An evaluation of invariance between and within
diagnostic groups over time', Alzheimers Disease and Associate Disorders, August 2010
PMID:21606904
Hoenig, H, Landerman,LR, Shipp, KM, Richardson,M, Pieper,C, Hubbard-Winkler, S, ‘A
Preliminary Predictive Model For Wheelchair Use 4 Months After Receipt’, Technology and
Disability Journal, (in press).
Huffman KM, Sloane R, Peterson MJ, Bosworth HB, Ekelund CC, Pearson MP, Howard T,
Pieper CF, Morey MC. The impact of self-reported arthritis and diabetes on response to a homebased physical activity counseling intervention. Scand J Rheumatol; April 2010 39:233-239.
PMC2963864
Huffman, KM, CA Slentz, LA Bateman, D Thompson, MJ Muehlbauer, JR Bain, RD Stevens,
BR Wenner, VB Kraus, CB Newgard, and WE Kraus. 2010. Exercise-induced changes in
metabolic intermediates, hormones, and inflammatory markers associated with improvements in
insulin sensitivity. Diabetes Care 32:1678-1683, 2009 PMCID: PMC3005483[Available on
2012/1/1]
Huffman KM, Slentz CA, Johnson JL, Samsa GP, Duscha BD, Tanner CJ, Annex BH, Houmard,
JA, Kraus WE. Impact of Hormone Replacement Therapy on Exercise Training-Induced
Improvements in Insulin Action in Sedentary Overweight Adults
Metabolism. Author manuscript; available in PMC 2009 July 1. Published in final edited form
as: Metabolism. 2008 July; 57(7): 888–895. doi: 10.1016/j.metabol.2008.01.034
PMCID: PMC2518063
Huffman KM, Hall KS, Sloane R, Peterson MJ, Bosworth HB, Ekelund CC, Pearson MP,
Howard T, Pieper CF, Morey MC. Does Diabetes Associate with poorer self-efficacy and
motivation for physical activity in older adults with arthritis? Scandinavian Journal of
Rheumatolog,. 1,2010 (in press). PMCID: PMC3058748
Hybels, C.F., Pieper, C.F., Blazer, D.G., Fillenbaum, G.G., & Steffens, D.C. Trajectories of
mobility and IADL function in older patients diagnosed with major depression. International
Journal of Geriatric Psychiatry, 2010, 25(1), 74-81. PMC2894462 (available 2011/1/1) DOI:
10/1002/gps.2300.
Kraus, VB, TB Kepler, TV Stabler, J Renner, and JM Jordan. 2010. First qualification study of
serum biomarkers as indicators of total body burden of osteoarthritis. PLoS ONE 5(3): e9739.
doi:10.1371/journal.pone.0009739 PMC2840035
Kraus, VB, TW Worrell, G McDaniel, CF Pieper and RE Coleman. 2010. Knee osteoarthritis is
a risk factor for contralateral ankle bone scintigraphy abnormality (in preparation). (is this
Association of bone scintigraphic abnormalities with knee malalignment and pain. Rheum Dis.
2009 Nov;68(11):1673-9. Epub 2008 Nov 3. PMID:18981032[PubMed - indexed for
MEDLINE]
Lee RH, Lyles KW, Colón-Emeric C. A review of the effect of anticonvulsant medications on
bone mineral density and fracture risk. Am J Geriatr Pharmacother 2010 Feb; 8(1):34-46.
PMCID: PMID:20226391
Mandelblatt JS, Sheppard VB, Hurria A, Kimmick G, Isaacs C, Taylor K, Kornblith AB, Noone
A, Luta G, Barry WT, Tallarico M, Hunegs L, Zon R, Naughton M, Winer E, Hudis C, Edge SB,
Cohen HJ, Muss H, Cancer Leukemia Group B. Breast cancer adjuvant chemotherapy decisions
in older women: the role of patient preference and interactions with physicians. J Clin Oncol.
2010 Jul 1;28(19):3146-53. PMID: 20516438
Muoio DM. Intramuscular triacyglycerol and insulin resistance: guilty as charged or wrongly
accused? Biochim Biophys Acta 2010 Mar; 1801(3):281-288. PMCID: PMID:19958841
Nelson, AE, YM Golightly, VB Kraus, T Stabler, JB Renner, CG Helmick, and JM Jordan. 2010.
Serum transforming growth factor-beta 1 is not a robust biomarker of incident and progressive
radiographic osteoarthritis at the hip and knee: The Johnston County Osteoarthritis Project.
Osteo Cartilage 18:825-829. PMC2746496
Ostbye, T. Malhotra, R. Landerman, L.R. Body mass trajectories through adulthood: results from
the National Longitudinal Survey of Youth 1979 Cohort (1981-2006).Int J Epidemiol. 2011
Feb;40(1):240-50. Epub 2010 Sep 5.PMID:20819785 [PubMed - in process]
Pavon J, Whitson HE, Okun M. Parkinson's disease in women: A call for improved clinical
studies and for comparative effectiveness research Maturitas 2010 April 65 (4): 352-358
PMC2875870
Peterson MJ, MC Morey, C Giuliani, CF Pieper, KR Everson, V Mercer, M Visser, JS Brach, SB
Kritchevsky, BH Goodpaster, S Rubin, S Satterfield, and EM Simonsick, for the Health, Aging
and Body Composition Study Research Group. Walking in old age and development of
metabolic syndrome: the Health ABC study. Metabolic Syndrome and Related Disorders, 8 (4),
2010. PMC3072703
Peterson MJ, Morey MC, Giuliani C, Pieper CF, Evenson KR, Mercer V, Visser M, Brach JS,
Kritchevsky SB, Goodpastor BH, Rubin S, Satterfield S, and Simonsick ES for the Health Aging
and Body Composition Study Research Group. Habitual walking for physical activity in old age
and development of metabolic syndrome: The Health ABC Study. Metabolic Syndromes and
Related Disorders, 2010 (in press). PMCID: PMC - In Process.
Tractenberg, R.E., Fillenbaum, G.G., Aisen, P.S., Liebke, D.E., Yumoto, F., & Kuchibhatla,
M.N. What the CERAD battery can tell us about executive function as a higher order cognitive
faculty. Current Gerontology & Geriatrics Research vol. 2010, article ID 510614, 10 pages,
2010. doi:10.1155/2010/510614. PMID:20585350 [PubMed - in process]
Whitson HE, Ansah D, Whitaker D, Potter G, Cousins SW, MacDonald H, Pieper CF,
Landerman L, Steffens D, Cohen HJ. Prevalence and patterns of comorbid cognitive impairment
in low vision rehabilitation Archives of Gerontology and Geriatrics 2010 Mar/Apr 50(2): 209212. PMC2815114
Whitson, HE, Sanders L, Pieper CF, Morey MC, Oddone EZ, Gold DT, Cohen HJ. Correlation
of symptoms to function in older adults with comorbidity. JAGS 57(4-April):676-682.
PMC2674624.
Whitson HE, Landerman LR, Newman AB, Fried LP, Pieper CF, Cohen HJ. Chronic medical
conditions and the sex-based disparity in disability: the Cardiovascular Health Study J Gerontol
A Biol Sci Med Sci. 2010 Dec;65(12):1325-31. Epub 2010 Jul 30. PMID: 20675619 [PubMed indexed for MEDLINE]
Zeng Y, Gu D, Purser JL, Hoenig H, Christakis N. Associations of environmental factors on
elderly health and mortality in China. Am J Public Health 2010 Feb; 100(2):298-305. PMCID:
PMC2804639
.Yang Li, Wen-Jing Wang, Huiqing Cao, Jiehua Lu, Chong Wu, Fang-Yuan Hu, Jian Guo, Ling
Zhao, Fan Yang, Yi-Xin Zhang, Wei Li, Gu-Yan Zheng, Hanbin Cui, Xiaomin Chen, Zhiming
Zhu, Hongbo He, Birong Dong, Xianming Mo, Yi Zeng, and Xiao-Li Tian. Genetic association
of FOXO1A and FOXO3A with longevity trait in Han Chinese populations Hum Mol Genet.
2009 December 15; 18(24): 4897–4904. Published online 2009 September 29.
doi: 10.1093/hmg/ddp459 PMCID: PMC2790334
Zhang L, Connelly JJ, Peppel K, Brian L, Shah SH, Nelson S, Crosslin DR, Wang T, Allen A,
Kraus WE, Gregory SG, Hauser ER, Freedman NJ. Aging-related atherosclerosis is exacerbated
by arterial expression of tumor necrosis factor receptor-1: evidence from mouse models and
human association studies. Hum Mol Genet. 2010 Jul 15;19(14):2754-66. PMID: 20421368
2011
Brummett, B.H., Michael A. Babyak, Grønbæk, M. and Barefoot, J.C. (2011). Positive emotion
is associated with 6-year change in functional status in individuals aged 60 and older, Journal of
Positive Psychology, in press.
Cheng AW, Stabler TV, Bolognesi M, Kraus VB. 2011. Selenomethionine inhibits IL-1β
inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2) expression in primary
human chondrocytes. Osteoarthritis Cartilage. 19:118-25. Epub 2010 Oct 28.NIHMSID
#249538. PMID: 21035557
Denoble, AE, KM Huffman, TV Stabler, SJ Kelly, MS Hershfield, GE McDaniel, RE Coleman
and VB Kraus. 2011. Uric acid is a danger signal of increasing risk for osteoarthritis through
inflammasome activation. PNAS U S A. 2011 Jan 18. [Epub ahead of print]
Ganesh, SP, Fried, LP, Taylor, DH, Pieper,CF, Hoenig, HM, 'Lower extremity physical
performance, self reported mobility difficulty, and use of compensatory strategies by elderly
women', Archives of Physical and Medical Rehabilitation, 2011, 92(2) 228-35.
Hall,K, Sloane,RJ, Pieper,CF, Peterson,MJ, Crowley,GM, Cowper,PA, McConnell,ES,
Bosworth,HB, Ekelund,CC, Morey,MC, "Long-Term Changes in Physical Activity Following a
One-Year Home-Based Physical Activity Counseling Program in Older Adults with Multiple
Morbidities," Journal of Aging Research, 2011, Article ID # 3 308407, PMC 3014677.
Huffman, KM, CA Slentz, LA Bateman, D Thompson, MJ Muehlbauer, JR Bain, RD Stevens,
BR Wenner, VB Kraus, CB Newgard, and WE Kraus. 2011. Exercise-induced changes in
metabolic intermediates, hormones, and inflammatory markers associated with improvements in
insulin sensitivity. Diabetes Care Jan;34:174-6. Epub 2010 Oct 4. PMID: 20921216.
Kraus VB. 2011. OARSI World Congress – Brussels 2011 Year in Review – Biochemical
Markers. 2011. Osteo Cartilage Feb 11. [Epub ahead of print]. PMID: 21320614.
Kraus, VB. 2011. Biomarkers and Osteoarthritis in Genomic and Personalized Medicine, 2nd
Edition, eds. GS, Ginsburg and HF Willard (in press).
Lum, H, R Sloane, KM Huffman, VB Kraus, DK Thompson, WE Kraus, JR Bain, RD Stevens,
CF Pieper, GA Taylor, CV Newgard, HJ Cohen and MC Morey. 2011. Plasma acylcarnitines are
associated with physical performance in elderly men. The Journals of Gerontology Series A:
Biological Sciences and Medical Sciences; doi: 10.1093/gerona/glr006. [Epub ahead of print].
PMID: 21367961.
McDaniel, G, J Renner, R Sloane, and VB Kraus. 2011. Association of knee and ankle
osteoarthritis with physical performance. Osteo Cartilage Feb 7. [Epub ahead of print].
NIHMS27223. PMID: 21310252.
Pieper, CF, Redman,LM, Bapkar, M, Roberts,SB, Racette,SB, Rochon,J, Martin,CK, Kraus,WE,
Das,S, Williamson,D, Ravussin,E for the CALERIE Study Group. 'Development of Adherence
Metrics for Caloric Restriction Interventions', Clinical Trials, (epub ahead of print)
Redman, LM, KM Huffman, LR Landerman, CF Pieper, JR Bain, MJ Muehlbauer, RD Stevens,
BR Wenner, VB Kraus, CB Newgard, WE Kraus and E Ravussin. 2011. Effect of caloric
restriction with and without exercise on metabolic intermediates in non-obese men and women. J
Clin Endocrinology & Metabolism Feb;96:E312-21. Epub 2010 Dec 1. PMID: 21123443.
Thompson, DK, RJ Sloane, JR Bain, RD Stevens, CB Newgard, CF Pieper and VB Kraus. 2011.
Diurnal variation of serum acylcarnitines and amino acids (in review).
In Press
Allen KD, Oddone EZ, Coffman CJ, Datta SK, Juntilla KA, Lindquist JH,Walker TA,
Weinberger M, BOSWORTH HB, Telephone-Based Self-Management of Osteoarthritis: A
Randomized, Controlled Trial. Annals of Internal Medicine. 2010 (In Press).
Kenjale, AA., Ham, KL., Stabler, T., Robbins, JL., Johnson, JL., VanBruggen, MD., Allen, JD.,
Privette, G., Yim, E., Kraus, WE., and Allen, JD. (2011). Dietary Nitrate Supplementation
Enhances Exercise Performance in Peripheral Arterial Disease. Journal of Applied Physiology.
RECOGNITION AND AWARDS
DUKE UNIVERSITY PEPPER CENTER
(2009-2010)
2008
William E. Kraus, M.D., Associate Professor of Medicine & Cell Biology
Appointed:
Fellow, American College of Cardiology
Fellow, American College of Sports Medicine
Fellow, American Heart Association, Nutrition, Physical Activity and Metabolism
Council
Miriam C. Morey, Ph.D., Associate Professor of Medicine
Division of Geriatrics, Duke University Medical Center and
Associate Director of Research, Geriatric Research, Education and Clinical Center,
Department of Veterans Affairs Medical Center, Co-PI, Duke Pepper Center
Honors:
Invited to serve on the Editorial Board of the Journal of Rehabilitation Research
and Development
Named, Chair of Gerontological Society of American Research Committee of
the Health Sciences Section.
Thomas J. Povsic M.D. Ph.D., Assistant Professor of Medicine
Division of Cardiology, Duke University Medical Center
Awards:
Merck-Society of Geriatric Cardiology Research Award
MEDUSA- Medtronic-Duke Strategic Alliance Research Award
Duke Clinical Research Institute Research Award
Edna and Fred L. Mandel, Jr. Foundation Young Investigator
Kenneth E. Schmader, M.D., Professor of Medicine, Duke University
Medical Center VA Medical Center
Appointed liaison officer from the American Geriatrics Society (AGS) to the Advisory
Committee on Immunization Practices at the Center for Disease Control.
Named Director of the Geriatric Research, Education, and Clinical Center (GRECC)
Chief, Division of Geriatrics in the Duke Department of Medicine
Heather E Whitson, M.D., Assistant Professor of Medicine, Division of Geriatrics
Duke University Medical Center
Honors:
Paul B. Beeson Career Development Award
2009
Jim Cavanaugh PT, PhD, NCS, Assistant Professor, UNE, Department of Physical Therapy
Honors:
Named 2009 Duke Pepper Center Scholar
Harvey Jay Cohen, M.D., Walter Kempner Professor and Chair, Department of Medicine,
Director, Center for the Study of Aging and Human Development
Honors:
2009 Research Mentoring Award, Duke University School of Medicine
Mavis P. Kelsey Lecturer, University of Texas MD Anderson Cancer Center
Paul Calabresi Award, Society of International Oncology and Geriatrics (SIOG)
Kim M. Huffman, MD, Ph.D., Assistant Professor of Medicine, Division of Rheumatology
Duke University Medical Center, Staff Physician, Physical Medicine and
Rehabilitation Durham Veterans Affairs Medical Center
Honors:
Named 2009 Duke Pepper Center Scholar
Timothy Koves, Assistant Professor of Medicine, Division of Geriatrics, Duke University
Medical Center
Honors:
2009 Ellison Medical Foundation New Scholar Award for a project entitled "Incomplete
beta-oxidation of fatty acids and age-associated muscle dysfunction"
Miriam C. Morey, Ph.D., Associate Professor of Medicine
Division of Geriatrics, Duke University Medical Center and
Associate Director of Research, Geriatric Research, Education and Clinical Center,
Department of Veterans Affairs Medical Centerr
Honors:
Appointed, Fellow American College of Sports Medicine
Named, Associate Editor Journal of Rehabilitation Research and Development
Article published in JAMA, May 13, 2009 selected as feature article for JAMA Report
video
Deborah M. Muoio, Ph.D., Associate Professor of Medicine, Endocrinology & Metabolism
Duke University Medical Center
Honors:
Named 2009 Duke Pepper Center Scholar
Jama L. Purser, Ph.D., Assistant Professor of Medicine, Division of Geriatrics,
Duke University Medical Center
Honors:
Named 2009 Duke Pepper Center Scholar
Kenneth E. Schmader, M.D., Professor of Medicine, Duke University
Medical Center VA Medical Center
Honors:
Appointed to Influenza Work Group, ACIP, Centers for Disease Control
Chair, American Geriatrics Society (AGS) Research Committee
Chair, VA Subcommittee, AGS
Editor in Chief, American Journal of Pharmacotherapy
Svati H. Shah, M.D., Assistant Professor, Department of Medicine – Cardiology
Duke University Medical Center
Honors:
Named 2009 Duke Pepper Center Scholar
Heather E Whitson, M.D., Assistant Professor of Medicine, Division of Geriatrics
Duke University Medical Center
Honors:
First Place Poster, “Evidence-Based Practice Promoting Nursing Excellence”
2009 VA Conference
Named 2009 Pepper Center Scholar
2010
Harvey Jay Cohen, M.D., Walter Kempner Professor and Chair, Department of Medicine,
Director, Center for the Study of Aging and Human Development
Honors:
SUNY Downstate Alumni Award for Master Teacher in Geriatric Medicine and Gerontology
B. J. Kennedy Award for Scientific Excellence in Geriatric Oncology (ASCO)
Maragatha Kuchibhatla, Ph.D., Associate Professor, Department of Biostatistics and
Bioinformatics, and Gerda G. Fillenbaum, Ph.D., Professor of Medical Psychology, Duke
University Medical Center
Honors:
Duke University's CTSA grant
Growth Mixture Modeling in Diverse Populations: A Randomized Depression Trial and
Depression in an Epidemiological Survey
Kenneth W. Lyles, M.D. Professor of Medicine, Division of Geriatrics
Honors:
Eugene A. Stead, Jr. MD Teaching Award
Virginia B. Kraus, M.D., Ph.D., Associate Professor of Medicine; Assistant Professor,
Pathology; and Assistant Professor, Surgery, Duke University Medical Center
Honors:
Elected President Elect of OARSI (the Osteoarthritis Research Society International)
William E. Kraus, M.D., Associate Professor of Medicine & Cell Biology, Duke University
Medical Center
Honors:
Elected as a Trustee to the Board of the American College of Cardiology for the
term 2010-2013
Kenneth Schmader, Professor of Medicine, Duke University Medical Center, VA Medical
Center
Honors:
Named to Adult Immunization and Influenza Work Groups, Advisory Committee on
Immunization Practices (ACIP), Centers for Disease Control (CDC)
2010 Duke Pepper Center Scholars
Jennifer Dungan, RN, PhD - Research Associate
School of Nursing
Timothy Koves, PhD - Assistant Professor
Medicine – Geriatrics
Thomas Povsic, MD – Assistant Professor
Medicine - Cardiology
Amy Pastva, PhD – Assistant Research Professor
Department of Community and Family Medicine
William Michael Foster, PhD - Research Professor
Medicine - Pulmonary and Critical Care Medicine
Matthew Peterson, PhD – Assistant Professor
Medicine - Geriatrics
Lee Jones, PhD – Associate Professor
Radiation Oncology
Kelli Allen, PhD – Associate Professor
General Internal Medicine
Jessica Chia, MD – Medical Instructor
Medicine – Pulmonary, Allergy and Critical Care Medicine
Jason Allen, PhD – Assistant Professor
Medicine - Cardiology
Gregory Sempowski, PhD – Associate Professor
Medicine – Duke Human Vaccine Institute
David Madden, PhD – Professor
Medicine – Psychiatry and Behaviorial Sciences
Beverly Brummett, M.D. – Associate Professor
Medicine – Medical Psychology
Helen Lum, MD – Medical Instructor/Duke Post Doctoral Training Program
Medicine - Geriatrics
2011
Harvey Jay Cohen, M.D., Walter Kempner Professor and Chair, Department of Medicine,
Director, Center for the Study of Aging and Human Development
Honor:
Honorary Doctor of Science & Commencement Speaker- SUNY Downstate
Katherine Hall, Ph.D., Junior Pepper Scholar, Post-doctoral Trainee, Durham VA GRECC
Honors:
Co-Chair of the Aging Special Interest Group (2011-2013), Society of Behavioral
Medicine:
Chair of the Emerging Scholars and Professional Organization Section (2011-2014),
Gerontological Society of America:
Kenneth W. Lyles, M.D. Professor of Medicine, Division of Geriatrics
Honor:
Elected, Secretary-Treasurer of the Paget Foundation
Miriam C. Morey, Ph.D., Associate Professor of Medicine, Division of Geriatrics, Duke
University Medical Center and Associate Director of Research, Geriatric Research,
Education and Clinical Center, Department of Veterans Affairs Medical Centerr
Honor:
Appointed to the Strategic Health Initiative of Aging of the American College of Sports
Medicine (2011-2014.
Heather E Whitson, M.D., Assistant Professor of Medicine, Division of Geriatrics
Duke University Medical Center
Honor:
Outstanding Service Award from the AGS Health Systems Innovation-Economics of
Technology Committee
Minority Research
The Duke University Pepper Center
(2009-2011)
General Brief Description of Minority Activities:
The Duke Pepper Center has a rich tradition of minority research that includes support of
minority trainees and a broad depth of research yielding extensive publications of relevance.
Special Projects
Genetic Ascertainment of Large African American Family for Osteoarthritis and Early
Onset Cardiovascular Disease.
Virginia Kraus, M.D., Ph.D., William Kraus, M.D., Project Leaders:
Funding Years 2001-ongoing
Drs. Virginia Byers Kraus and William E. Kraus, in collaboration with the Duke Pepper Center
and the Duke Center for Human Genetics, have genetically ascertained one of the largest intact
extended families in the United States. Particular emphasis was placed on evaluating this family
(Family C) for osteoarthritis and early onset heart disease. This family celebrated a reunion in
Durham, NC, July 24-28, 2002. A total of 500 adults participated from 35 states. This family
traces its origin back to 1773 and consists of a mixture of ethnicities: primarily American Indian
mixed with Anglo-Saxon and African-American. This is believed to represent one of the oldest
intact extended families in the United States. Large family reunions have been held every two
years since 1978 and every four years in North Carolina. A family genealogy has been published
encompassing the years 1773 to approximately 1950. Of note, the author, approximately aged
86, is still living in North Carolina. We ascertained 239 members of this family at a Health Fair.
We obtained health information, family history information along with laboratory data for use as
quantitative traits including glucose and lipids. In addition, a physical exam was obtained which
included body mass index, weight, height, calcaneal bone mineral density, hand exam for OA,
blood pressure, eye exam for glaucoma and retinopathy, and a physical function measure on the
over 65 age group. A pedigree has been constructed consisting of four generations. In addition
to phenotyping and genetic ascertainment, we provided educational medical workshops on
osteoporosis, osteoarthritis and cardiovascular disease. We are working to connect the four
generations in the pedigree back to the original founders utilizing information provided in the
Family C geneology and information provided by the family geneologist who has kept current
records for the family. We now have these in hand. We plan to proceed with interviews of older
family members remaining in North Carolina to try to fill in any pedigree gaps. We will also
proceed with evaluating the pedigree for medical conditions that appear to run in the family. We
will then proceed to apply for funding to support genetics research on this family.
1
The Johns Hopkins University
Claude D. Pepper Older Americans Independence Center
2011 OAIC Annual Directory
Jeremy Walston, M.D., Principal Investigator
410-550-1003
410-550-2513 FAX
[email protected]
Karen Bandeen-Roche, Ph.D., Co-PI
410-955-3067
410-955-0958 FAX
[email protected]
Brian Buta, MHS, Administrator
410-502-3412
410-614-9625 FAX
[email protected]
I.
DESCRIPTION OF CENTER
The Johns Hopkins Older Americans Independence Center (OAIC) was established in June 2003 in
order to support and develop the next generation of research and researchers necessary to determine
causes and treatments for frailty in older adults. The specific aims for this OAIC were selected to
propel and translate research on frailty across the Johns Hopkins Medical Institutions, and in
collaborations between OAICs. We aim to 1) stimulate, lead and sustain our interdisciplinary research
program to define the etiology and manifestations of frailty in older adults, and to translate this into
prevention and treatments to ameliorate frailty or prevent its onset, and ensure ever-increasing
visibility for this work internally and externally; 2) provide key infrastructure and access to emerging
technologies and analytical strategies through our two research cores, Genetics, Genomics and
Molecular Core, and Biostatistics Core; 3) develop new, innovative methodologies, research strategies
and technologies essential to the study of the complex syndrome of frailty (including systems biology,
molecular biology, genetics, epigenetics, and genetic epidemiology, as well as in new approaches to
data acquisition and data analysis of complex nonlinear systems); 4) attract outstanding investigators to
the field of frailty research, and supporting and nurturing their skills, translational abilities and career
development in this area; 5) identify and support pilot studies that will address next-stage hypotheses
and evaluate potential interventions for diagnosis, screening, prevention or amelioration of frailty; 6)
serve as a local and national resource for scientific, analytic and methodologic advice and collaboration
to investigators in the area of research on frailty in aging. The home base for this Center is in the
Johns Hopkins Center on Aging and Health, a Center of Excellence for Aging Research jointly
sponsored by the Schools of Medicine, Nursing, and Public Health.
II.
RESEARCH, RESOURCES AND ACTIVITIES
II.A.
RC-1: BIOSTATISTICS CORE
Karen Bandeen-Roche, Ph.D., Core Leader
410-955-1166
410-955-0958 FAX
[email protected]
Qian-Li Xue, Ph.D., Core Director
410-502-7808
410-614-3755 FAX
[email protected]
The Biostatistics Core is dedicated to empowering our institution’s scientists with the quantitative
support and expertise needed to create, and translate into clinical practice, the next generations of
research on frailty. It works to achieve this aim through the provision of first-rate statistical reasoning
and database resources to OAIC-affiliated research projects; the development and support of new
methodologies that are essential to studying the complex syndrome of frailty; and the mentoring in
quantitative methods of junior investigators with promise to develop into leaders in research on frailty.
We now proceed to report on progress made in year eight toward achieving each of the five core
specific aims. Under each aim, we summarize projects using Core resources and new and enhanced
services made available for researchers on frailty at our institution.
Aim 1: Stimulate and advance research on frailty at our institution:
Aim 1-a. Provide analytic and data management support for high priority research on frailty.
During this reporting period, this Core has assisted 8 researchers in 13 projects on frailty, including the
design, development, and implementation of data systems; data acquisition and cleaning; refinement of
study hypotheses; study design; design and implementation of data analyses; and preparation of
manuscripts, presentations, and applications for research funding. This support has resulted in 9
publications so far; 1 grant has been submitted and 3 are in preparation.
Creation of sound designs for supported studies and future R01s: We first summarize design
contributions for emerging studies made by this Core over the period 7/1/10 to 4/30/11.
Project 1 - Low intensity physical activity and physical and cognitive function (Michelle Carlson): this
R01 grant proposal seeks to innovatively augment real-time fMRI and step activity methods Dr.
Carlson and others have validated in 120 physically and neurocognitively well-characterized
community-dwelling older adults who have been followed 1-2 years post-Experience Corps Trial by
surveying in real-time lifestyle activities in their day-to-day lives using complementary mobile
Smartphone and GPS technologies over a 1-year period and link their activity patterns to their
neurocognitive and functional health. Dr. Xue collaborated with Dr. Carlson in the study design and
the development of statistical analysis plan. The Biostatistics Core provided preliminary analyses
supporting the proposal.
Project 2 – CMV and immune function in older adults (Sean Leng): The objective of this R01 grant
proposal is to characterize chronic CMV infection beyond IgG serology and its relationships with
immunosenescence and distal outcomes in the Women’s Health and Aging Studies (WHAS) I & II and
InCHIANTI study, three large NIA-funded cohort studies of community-dwelling older women and
men with banked serum and cell samples of up to 14-yr longitudinal follow-up. As co-investigator on
this proposal, Dr. Xue is developing an analytic plan for this proposal.
Project 3 – Clinical significance of short-term trajectories of change in muscle strength (Qian-Li Xue):
This R03 grant proposes to 1) characterize the short-term (6-month) change and variability of grip
strength in the Women’s Health and Aging Weekly Substudy; and 2) validate the clinical
meaningfulness of the intra-person variability in grip strength by examine: a) whether the variability
precedes, occur in parallel, or succeed acute intercurrent health events, and b) whether the variability
predicts long-term trajectory of grip strength and adverse health outcomes including mortality and
ADL and IADL dependency. As the PI of this proposal, Dr. Xue will lead the development of the
study design and analysis.
Project 4 – Center of Excellence in Clinical Preventive Services (Cynthia Boyd, former RCDC
trainee): This P01 grant responds to a recent RFA calling for research centers to foster innovative,
synergistic, and targeted research on clinical preventive services. The application proposes to
conduct 3 projects related to safety for older patients for whom issues of the balance of benefit and
harms of preventive services are particularly challenging: those with and 2 or more co-existing
conditions. Such patients are particularly vulnerable and at risk for frailty, the topic focus of this
OAIC. Therefore, the proposed work is highly relevant to the promotion of independence for frail
older adults. As co-investigator, Dr. Bandeen-Roche will develop the analytic plan for one of the three
projects and serve on the leadership team for the Center as a whole.
Performing statistical analyses to validly address scientific aims: The Biostatistics Core is also
actively engaged in furthering existing research projects. Our collaboration is of two types: that
involving the provision of support to projects initiated outside our OAIC (“External Projects”), and
that integrated within projects supported by our OAIC (“Core Supported”). Support provided in year 8
is described below:
External Projects
(1)
Cytomegalovirus (CMV) DNA in peripheral monocytes is associated with elevated neopterin
levels in community-dwelling older adults (Sean Leng, a former RCDC trainee) - This study was to
investigate the relationship between chronic CMV infection evidenced by detectable CMV DNA in
peripheral monocytes and serum neopterin levels in community-dwelling older adults over 70 years of
age. It is hypothesized that chronic CMV infection is associated with elevated neopterin levels,
independent of IFN-α. Addressing this hypothesis will provide initial insight into the role of chronic
CMV infection in monocyte/macrophage-mediated immune activation in the elderly. The project
started in Year 7 and continued in Year 8. Dr. Xue provided statistical consultation to this project and
the Biostatistics Core conducted the data analysis. A manuscript is in press.
(2)
Treatment Burden in Older Adults with Multimorbidity (Cynthia Boyd): The overall goal of
this project is to develop an improved understanding of the concept of treatment burden and to develop
a practical tool for assessing treatment burden among older patients with multimorbidity to assist in
medical decision making. We have conducted a cross-sectional secondary data analysis of baseline
data on older adults with multimorbidity (n=904) who enrolled in an ongoing RCT of Guided Care.
We generated and validated a scale (0-16) of self-reported difficulty with health care management
tasks based on 8 questions. Patient-reported quality of care, mental and physical health, number of
chronic conditions and conditions that add to health status complexity (falls, visual, and hearing
impairment) were examined; and their associations with the health care difficulty scale were tested. A
draft of a paper summarizing the results of this analysis is completed and ready for submission.
Currently, we are conducting longitudinal analyses to assess the effect of individual-level change in
patient activation on change in the healthcare difficulty score, as well as the effects of change in the
healthcare difficulty score on change in physical and mental health and patient reported quality of care.
With mentoring from Drs. Bandeen-Roche and Xue as well as others, Dr. Boyd has successfully
obtained a K-Beeson grant award to further her research career in this direction.
(3)
The Baltimore Experience Corps® Trial (BECT) (George Rebok): The EC trial is a randomized
controlled trial that places people 60 and older either as volunteers in public elementary schools in
roles that were designed to improve academic outcomes in the schools while promoting the health of
the older adults, or as control participants receiving low-intensity volunteer alternatives. The trial is
currently in its fourth year of evaluation. It was proposed in our last renewal application as an external
project for this OAIC because of funding shortfalls restricting the resources available to it for data
analysis. Drs, Xue and Yu and Mr. Tao Wang have been providing statistical consultation and support
to the study on the analyses of baseline data to (1) validate a new generativity scale that is comprised
of three subdomains: generative desire, generative behavior, and generative fulfillment; and (2)
complete the work on examining motives of a diverse sample of primarily African-American (AA)
older adults for participating in this trial, and analyze associations between motives and recruitment
strategies. Two papers are in the final stage of editing.
Core Supported Projects
Pilot project 1: Physiology of vestibular dysfunction and clinical implications (Yuri Agrawal,
M.D.) – The study aims to characterize the physiologic nature of the vestibular dysfunction that occurs
with aging, and to evaluate whether specific deficits of the vestibular system (semicircular canal or
otolith dysfunction) are associated with distinct clinical manifestations and consequences. Findings
from this study will be used to guide the development and testing of rational screening, vestibular
rehabilitation, frailty and fall risk reduction strategies in older individuals. Dr. Long He, database
manager of Biostat Core, has developed an Access database for study data entry and archive.
(1)
Pilot project 2: Insulin Resistance, Energy Homeostasis, and Frailty (Rita Kalyani, Ph.D.) –
This pilot aims to: 1) determine differences in fasting glucose and insulin levels, related differences in
hormones and inflammatory markers associated with energy metabolism (GLP-1, adiponectin, leptin,
resistin, ghrelin, growth hormone, IGF-1, IL-6), and whether frail compared to nonfrail or prefrail
older women demonstrate hormonal or inflammatory responses to dynamic glucose testing that are
deficient, exaggerated, delayed, prolonged and/or show threshold patterns of response; and 2)
determine whether differences in the above hormonal and inflammatory regulators of energy
metabolism are also observed under fasting and challenge conditions among older women with
sarcopenia compared to women without sarcopenia. Dr. Xue has provided statistical consultation to the
project. This work has resulted in 1 submitted paper and 1abstract submission to 2011 GSA.
(2)
Pilot project 3: Inflammation, Hormonal Alteration and mTOR Signaling in Modulating Agerelated Declines in Muscle Strength (Qian-Li Xue, Ph.D.) – The proposed project is guided by the
network theory of aging to explore the benefits of multisystem intervention by conducting a pilot trial
to evaluate the efficacy of a combined exercise, rapamycin, and growth hormone intervention in
ameliorating age-related decline in muscle strength in high and low capacity runner (LCR) rats. In
collaboration with Dr. Leng (a geriatrician-scientist and immunogerontologist) and Dr. David Sharp (a
basic scientist from University of Texas Health Science Center at San Antonio), Dr. Xue is completing
the planning phase of the trial and the trial will begin in May 2011.
(3)
RCDC project 1: Use of p16INK4a Transcriptional Factor Level as a Marker of Molecular Age
and Predictor of Perioperative Outcomes (Aliaksei Pustavoitau): this project led by Dr. Pustavoitau
tries to establish the biological role and clinical utility of biomarkers of aging in the perioperative
period. Once their utility is identified, the biomarkers can be incorporated into models of perioperative
outcomes in various patient populations. Specifically, Dr. Pustavoitau proposes to investigate a
predictive role of transcriptional factor p16INK4a (p16) as a biomarker of aging in patients undergoing
elective coronary artery bypass surgery. Dr. Bandeen-Roche has consulted with Dr. Pustavoitau on his
statistical plan, and Long He is developing a web-based data collection system for this study.
(4)
(5)
RCDC project 2: Hearing loss and frailty (Frank Lin): Dr. Lin uses publicly-available
NHANES data to examine the epidemiology of hearing loss in the elderly and the association of
hearing loss with social isolation and functioning. He has had one manuscript examining hearing loss
epidemiology in older adults >70 recently published. Two other manuscripts are currently under
review (one manuscript demonstrating an association between skin color (as measured by Fitzpatrick
skin type) and hearing loss, and the other manuscript demonstrating an association of hearing loss with
cognition using the Digit Symbol Substitution Test). Dr. Varadhan and our student analyst Paige Maas
provided statistical consultation and analytic support to this work. In particular, Dr. Varadhan and Ms.
Maas have developed new ways to analyze audiometric data that would allow researchers to draw
better statistical inferences when studying risk factors and possible treatment modalities for hearing
loss. This work has resulted in a 1st place award at the 4th Annual Research on Aging Showcase poster
competition organized by the Center on Aging and Health and the School of Public Health
Gerontology Interest Group in April 2011.
RCDC project 3: Effects of a Lifestyle Intervention in Older Adults with Sleep Apnea (Devon
Dobrosielski): The specific aims of this project are to: 1) determine the effectiveness of a lifestyle
intervention, consisting of a weight loss diet and supervised exercise, on reducing sleep apnea in older
adults, 2) determine whether this intervention is effective at improving parameters that are common to
both sleep apnea and frailty, such as poor physical functional capacity and body composition, impaired
or abnormal cardiovascular and metabolic function and increased levels of inflammation. Drs.
Bandeen-Roche and Xue are working provides consultation to Dr. Dobrosielski on the design and
analysis of the trial.
(6)
Core Project 1: Changes in anabolic hormone levels and the development of fatigue in Older
Women (Qian-Li Xue): Feeling fatigued is a common complaint among older adults and is associated
with reduced likelihood of walking outside of home, decline in gait speed, and mortality. This study
performs joint analysis of cross-sectional and longitudinal associations of anabolic hormones (DHEAS,
IGF-1, and Testosterone) with fatigue. This study will advance research in this direction by quantifying
the interrelationships among rates and patterns of changes in anabolic hormones and their impact on
the development of fatigue, thereby providing a unique opportunity to understand the hormonal
pathway by which multiple hormonal deficiencies independently and jointly lead to fatigue. The data
analysis is completed and a manuscript is under development.
(7)
Core Project 2: Vitamin D trial (Paulo Chaves): This pilot intervention study examines the
impact of vitamin D supplementation in pre-frail individuals with insufficient vitamin D levels on
inflammatory mediators and on physical and cognitive function outcomes. This study is led by Dr.
Chaves in the RCDC Clinical Translation Unit. The Biostatistics core has been leading the
development of data collection forms, randomization algorithms, and database creation. Dr. BandeenRoche provided consultation on study design and power calculation for the trial.
(8)
Collaboration with the Genetics Core: Dr. Xue is a regular participant in the biweekly meetings held
by our Genetics Core. He serves as a statistical consultant on the analyses linking genotypes to
phenotypes of muscle strength and frailty in WHAS AND CHS. We currently devote one full time
analyst to genetics-oriented analyses (Wenliang Yao); he is a fully integrated member of our Core
analysis team who sits together in our group and is mentored by Dr. Xue. Members of the Genetics
Core join in our biweekly Biostatistics Core meetings periodically as projects of their oversight are
discussed.
Aim 1-b. New methodologies for data analysis essential to studying the complex syndrome of
frailty:
Dr. Varadhan, in collaboration with Dr. Hong Zhu, is developing network models to study frailty as a
dynamical system. The goal is to characterize how the topological properties of a network (e.g. degree
of scale free networks, entropy of networks) are related to properties of dynamics on the network
including time-to-equilibrium, long-range correlations, fractal scaling, power-law exponent. This
project provides insights on the relationship between the network structure and the properties of its
dynamic evolution in response to stimulus. This study helps to identify network structural properties
that would make them frail in terms of exhibiting lack of resilience in response to stimulus. Initial
parts of this work were presented as a poster at the Geriatric Showcase Celebration at Bayview
Medical Campus on May 27, 2010, and the poster won the first prize.
The investigators now have evidence from simulation studies suggesting that the entropy of the
network, as defined in Demetrius and Manke (2004), might play a critical role in the resilience of the
network to perturbations. They are now working on developing a strategy to generate Boolean
networks with specified entropy in order to better characterize the relationship between entropy and
dynamic properties of stimulus-response such as time to recovery and long-range correlations in the
response. They hope to complete this work by October 2011 and submit a manuscript to mathematical
biology journal. They will also present the results of this work in an invited symposium on Complex
Systems Approaches in Aging at the Gerontological Society of America 2011 in Boston, organized by
Dr. Lew Lipsitz of Harvard University and Dr. Heather Whitston of Duke University.
Aim 2. Provide resources in data infrastructure and emerging computing technologies.
A web-based grant management system was developed and implemented to facilitate internal grant
administration by the Johns Hopkins OAIC and the Division of Geriatric Medicine and Gerontology.
This online tool is able to address the critical needs of the research administration by streamlining the
process of grant submission, preparation, review, and approval. The tool contains two inter-linked
modules that support two groups of users: PIs and grant administrators, with interactive and userfriendly features built in to address the specific needs of the respective user groups. For PIs, it provides
step-by-step guidance on when and how to collect and compile grant related materials such as
subcontracts, biosketch, letters of support, and budget justification. The PI is also requested to fill out
an online survey that encourages the PI to think proactively about the analytic and data management
support needs for the project; and the survey data can then be used for effective budget and resource
allocation planning during early stage of the proposal development. To assist the PI to stay on track
and meet internal processing deadlines, automatic email reminders of upcoming deadline and
notifications for completion or past-due status of major steps will be sent to the PI. For grant
administrators, various reporting and query functions are added to allow real-time monitoring and
reporting of all pending and submitted grants by investigator, deadline, and completion status. All the
interactions between the PI and the administrator are logged into a searchable database. We have
received very positive feedback since the launch of this online tool in April 2011. We are currently
being asked by Research Administration in the Department of Medicine to help design and implement
a similar system for the whole department.
Additional contributions to data infrastructure are detailed under Aims 4 and 5 below.
Aim 3. Mentor junior faculty
In so doing we aim to optimize for junior faculty the access to the research expertise and support we
provide; usage of modern database and analytic resources; and effectiveness of collaboration with
statistical colleagues. We outline progress in each of these areas:
Access to research expertise and support: We dedicate ourselves to supporting research led by
each RCDC investigator. Support provided in the current year has been outlined under “Core
Supported Projects” under Aim 1-a. Dr. Bandeen-Roche (Lin, Pustavoitau) or Dr. Xue (Lin,
Dobrosielski) has mentored and collaborated with each RCDC awardee, providing individualized
explication of statistical techniques as well as more general mentoring. Support has spanned study
design, analytic design and implementation, and data management.
In the current year our core continues to play a central role in the Pepper Scholars program.
Accomplishments are detailed in the Leadership / Administrative Core section of our report. In
brief, the program consists of monthly research-in-progress sessions that assemble currently and
formerly supported RCDC and pilot faculty as well as other junior faculty and trainees on aging.
This initiative was spearheaded last year by our LAC with primary developmental leadership from
Dr. Bandeen-Roche and our program administrator, Mr. Buta. The program aims to feedback for
research in a formative stage, connect junior faculty to resources and collaborators that can broaden
their reach and strengthen their research quality, and strengthen the network for research on frailty
at our institution. The Scholars sessions have become a fixture of our program, occurring faithfully
on a monthly basis. More detail is provided LAC section above.
Our OAIC has had a particularly successful year in the mentorship of its junior faculty toward the
receipt of career development awards, and our Core is proud to have engaged actively to this end.
RCDC-supported faculty Peter Abadir, Frank Lin, and George Wang all received K awards. Dr.
Bandeen-Roche worked closely with Dr. Lin on his application, and Dr. Xue closely advised the
applications of Drs. Abadir and Wang. There were also a record number of Brookdale Leadership
in Aging Fellowship applications from our institution this year. Dr. Bandeen-Roche provided
detailed review and feedback to five of these. One of only two 2011 fellows named was Dr. Ravi
Varadhan, a biostatistician and former RCDC-supported faculty and recipient of Development
Project funding from this Core. Dr. Varadhan will pursue research to better delineate the
applicability of intervention trial findings to older adults.
Aim 4. Heighten the visibility of our center’s research.
We have detailed our collaboration in supporting the research and mentoring activities of the OAIC
Cores throughout the previous narrative. Dr. Bandeen-Roche or Dr. Xue has participated in each of
the LAC meetings held to date, and most meetings have seen participation by both.
In 2010 we initiated a joint methods symposium series between our group and our sister OAIC at the
University of Maryland OAIC. These sessions have proven a great success. The 2nd symposium took
place on December 6, 2010 from 2:00 - 5:00pm. It consists of three sessions focused on longitudinal
analysis. In a first talk, Dr. John Sorkin (UMAB) gave an introductory review of cross-sectional, time
series, and longitudinal approaches. In the second talk, Dr. Qian-Li Xue (Hopkins) provided a practical
guide to the selection, analysis and interpretation of longitudinal analyses. A final talk introduced the
growth mixture models through a real example using data from the ADAPT trial. Topics under
development for future symposia include missing data, causal inference, and competing risks.
Dr. Bandeen-Roche continues to serve on the external advisory committee for the Duke OAIC. She
served on the special emphasis panel that reviewed OAIC applications in February, 2011.
Aim 5. Provide critical resources for the translation of frailty research into clinical interventions
and practice.
We have worked to achieve this by all of the means detailed above. Of particular relevance for
translation is our support for external projects 2 and 3 as well as the RCDC project of Devon
Dobrosielski (Aim 1a). Additionally we provide support in database design, study design, and analysis
in conjunction with our Clinical Translation Unit, whose accomplishments are detailed in the RCDC
section. Specifically we have provided database infrastructure for the CTU Frailty Registry of
potential participants for clinical translational studies and contributed to the development of the study
design, database, and statistical analysis plan for the pilot trial of vitamin D supplementation for the
amelioration of functional decline in pre-frail older adults now being initiated by this OAIC.
II.B.
RC-2: GENETICS, GENOMICS AND MOLECULAR CORE
Aravinda Chakravarti, Ph.D., Core Leader
410-502-7525
410-502-7544
[email protected]
Jeremy Walston, M.D., Core Co-Director
410-550-1003
410-550-2116 FAX
[email protected]
Dan-Arking, Ph.D., Core Co-Director
410-502-7531
410-502-7544 FAX
[email protected]
M. Daniele Fallin, Ph.D., Core Co-Director
410-955-3463
410-955-0863 FAX
[email protected]
The purpose of RC-2 is to provide the human resources, infrastructure, and training necessary to
facilitate the highest quality contemporary biological studies related to frailty, the overall focus of the
Hopkins OAIC. The resources provided by this core to frailty researchers include 1) leading interdisciplinary expertise for the design and implementation of molecular, genetic and genomic studies
related to frailty; 2) access to state-of-the-art genetic, genomic and molecular technologies; 3) access
to a diversity of human and frail animal model DNA, tissue and serum samples; 4) mentorship and
training in genetics, genomics, and molecular biology; and 5) expertise to help translate molecular,
genetic and genomic findings to clinically meaningful interventions. By providing these intellectual
and physical resources, RC-2 facilitates the elucidation of clinically relevant biological pathways that
underlie frailty and related biological vulnerability, and thereby identify promising targets toward
which to develop interventions that prevent or attenuate frailty. The last several years of RC-2 funding
have produced significant progress towards these goals through: the establishment of state-of-the-art
infrastructure for genetic data generation and analyses related to frailty; the assemblage of a highlyskilled multidisciplinary team of experienced investigators; and important scientific progress related to
frailty, including the development of novel endophenotypes, the identification of critical molecular
pathways associated with frailty, and the development and characterization of a frail mouse model. As
a result of this progress, RC-2 and its leadership has become a national resource for the development of
frailty and aging-related genetics research as measured by publications, award-winning national
symposia, consortium building efforts for combining and studying populations of older adults,
development and funding of collaborative genetics studies with investigators across the country, and
provision of training and mentorship for the next generation of investigators interested in studying the
molecular and genetic basis of frailty and its translation into clinical care.
In year eight of our award, we continue to expand the scope of RC-2 beyond human genetics studies
into a comprehensive genetics, genomics, and molecular core that builds on the evolving science,
infrastructure, and expertise developed in the first years of this center. This evolution requires the
leveraging of additional human and infrastructure resources from across the Johns Hopkins Medical
Institutions towards frailty research, and includes facilitating access to senior leaders with necessary
expertise and infrastructure and to a) facilitate analytical strategies needed to analyze the vast amounts
of genetics and genomics data being generated, b) incorporate measurements of oxidative stress,
mitochondrial function, DNA methylation, and gene expression into RC-2 sponsored frailty research,
and c) develop improved access to human and/or animal biological samples and phenotypic data for
needed for additional frailty research. This next stage of goals and advances enables RC-2 to continue
to support the most rigorous human genetic studies related to frailty while at the same time enabling it
to expand its scope to support studies of molecular pathways identified in genetics studies related to
human frailty. We have provided assay development support and biological expertise regarding
etiology of a hearing loss and vestibular system changes to all of our RCDC supported and PESC
supported scholars. In addition, we continue to provide a wide range of external support to individual
investigators from across JHU and nationally regarding frailty phenotype development, frailty
measurement, human genetics expertise, mouse model development expertise, renin-angiotensin
system expertise, and in the use of frailty as a risk factor for organ transplantation failure.
In taking the necessary steps for the further development of this scientific agenda, and in facilitating
the development of the most rigorous genetic, genomic, and molecular studies with translatable
potential, the specific aims of the Genetics, Genomics and Molecular core are:
Specific Aim 1: To provide interdisciplinary scientific expertise necessary to support the development
of the highest quality basic science research related to frailty including:
a. human genetics studies related to frailty. This support is provided by an established and
experienced multidisciplinary team offering scientific guidance for high quality study design,
the development of relevant endophenotypes, selection of genotyping and/or sequencing
technologies, and comprehensive structural and functional analysis of human genetics data.
b. epigenetic studies related to frailty. This support is provided through the further development
and adaptation of DNA methylation technologies presently utilized in cancer research at the
Johns Hopkins Medical Institutions (JHMI) and through collaborative relationships with DNA
methylation measurement experts.
c. altered gene and protein expression in frailty. This support is provided through our leverage of
state-of-the art technology and genomic analysis, senior expertise, mentorship, and leadership
available at JHMI towards frailty research.
d. mitochondrial and oxidative stress studies in frailty. This support helps focus scientific and
mentorial expertise as well as infrastructure at JHMI into the field of frailty research.
e. bioinformatics necessary to integrate and interpret biological data related to frailty.
Specific Aim 2: To provide the infrastructure necessary to facilitate cost-effective and efficient basic
frailty research through greater access to technology (2A) and biological samples (2B). Specifically,
RC-2 aims to:
2A: Provide state-of-the-art genetic and molecular biology infrastructure and technology relevant to
frailty research. These include:
a. provision of access to genetic technology that will facilitate highest quality human genetics
studies, including 1) genotyping for studies that range from small-scale single nucleotide
polymorphisms (SNPs) through large-scale, high-throughput genome-wide scans, 2) DNA
sequencing of genes implicated in association or candidate gene studies as being functionally
relevant to the frailty phenotype, 3) SNP search methodology necessary to identify relevant
genotypes and haplotypes in both genomic and mitochondrial DNA and 4) access to the highest
caliber genetic data analysis tools tailored to studies ranging from small-scale association
studies to genome-wide approaches.
b. provision of access to genome-wide and gene-specific methylation analysis for epigenetic
studies that may reveal critical regulatory processes that influence frailty
c. provision of access to technology and training necessary to measure mitochondrial function and
oxidative stress
d. provision of access to gene expression technologies that enhances results identified in genetic,
epigenetic, and oxidative stress and mitochondrial studies related to aging and frailty.
e. provision of integrated bioinformatics (with RC-1) that enables analysis and interpretation of
frailty-related biological data.
2B: Provide access to biological samples, animal models, and biological data for OAIC-sponsored
investigators interested in frailty research through:
a. establishing and maintaining a repository of human DNA, serum, immune system cells, and
tissue samples.
b. providing ready access to mouse models of frailty and biological samples derived from frail
mouse models, including the IL-10-/- frail mouse model previously developed in part by RC-2
support.
c. providing access to an institutionally supported mouse phenotyping data base related to frailty
in order to facilitate the identification and utilization of other mouse models with frailty or
related phenotypes.
d. developing and providing access to merged national, population-based data sets relevant to
molecular and genetic frailty research in close collaboration with RC-1 and sponsoring studies.
Specific Aim 3. To attract and provide training, mentorship and resources to junior faculty supported
by RC-1, RC-2, RCDC and pilot cores and from across the institution through provision of access to
state-of the art technologies and senior leadership that enable the skill set development necessary to
design and conduct the highest quality molecular and genetic studies related to frailty.
Specific Aim 4. To provide optimal institutional and national visibility for RC-2-related science and
activities in order to attract scientists with important skill and knowledge sets highly relevant to frailty
research, and to stimulate meaningful translational research that bridges genetic and molecular findings
to interventions that treat or prevent the development of frailty in older adults. This is accomplished
by continuing to organize and provide educational programs at local, national and international forums,
through the identification of key faculty members and new and cutting edge molecular technologies
that may be relevant to frailty research at the Johns Hopkins Medical Institutions, and through ongoing
collaboration with all OAIC cores.
Specific Aim 5: To facilitate the translation of genetic and/or molecular findings relevant to frailty
into intervention or prevention-focused clinical studies through the provision of scientific guidance,
mentorship, and close collaboration with leadership of LAC, RC-1, RCDC, and pilot cores.
Core Progress, Year 8 (2010-2011)
Introduction: The major goals of Genetics, Genomics and Molecular Core at initiation of this OAIC
were to provide: scientific guidance and expertise for the development of human genetic proposals
related to frailty; state-of the art genotyping and sequencing infrastructure for OAIC funded projects;
training and mentorship to junior investigators interested in developing genetic proposals related to
frailty; and high profile local and national visibility that would attract new investigators to frailty
research. As summarized in Table 1, we continue to make substantial progress towards the
accomplishment of our specific aims, and important development advancements and significant
scientific discoveries continue to accelerate, , and high visibility for this core and center has been
attained. In addition, great strides have been made in the past year towards bringing junior and senior
investigators from across the Johns Hopkins Medical Institutions (JHMI) into OAIC frailty and aging
research. Individuals from external institutions have also received support from RC-2 structures and
processes for frailty research, providing additional evidence of the growing significance of this field to
medical investigators from multiple scientific disciplines.
RC-2, Table 1: Updated Overview of Structures, Processes, Outcomes for RC-2 (Genetics,
Genomics and Molecular Core)
Structures
Process
Outcomes
The establishment of a
Leadership and provision
The establishment of a frailty
committed multidisciplinary of scientific expertise for
phenotype and ongoing
leadership team
genetic, genomic and
endophenotypes development (in
with nationally recognized
molecular frailty research.
collaboration with RC-1).
expertise in human genetics,
Ongoing collaborative
The development and application of
genetic
agreements with
new genotyping and analytical
epidemiology, and geriatric
investigators from 4 major
methodology to large genetic
medicine.
NIH sponsored aging
consortium studies.
The establishment of
populations studies, and with
The development and utilization of a
highest quality, state-of-thetwo large GWAS and
frail mouse model by multiple
art genotyping
candidate gene consortiums
investigators exploring questions
and analytical infrastructure
to facilitate ongoing genetic
related to frailty and late life decline.
for investigators performing
studies related to frailty.
Multiple manuscripts published or in
frailty research.
Recruitment of necessary process.
The establishment of a
expertise to frailty.
Multiple grants related to frailty
research network of senior
Administration and
developed and funded.
scientists at Johns Hopkins
organizing of core functions
National symposia showcasing
who have needed expertise in through regular meetings,
developmental efforts and scientific
epigenetics, mitochondrial
developing and monitoring.
results.
biology, and
Training of junior
Recruitment of over 30 junior and
genomic/proteomic expertise. investigators.
senior faculty and new trainees to
frailty research, and over the past year
the recruitment of 3 graduate students
and 3 post-docs to frailty research.
This core continues to support multiple human genetic projects that benefit greatly from the team,
infrastructure and extramural funding that we have developed over the past several years related to
human genetics. In accordance with our mission to broaden our funded studies and investigators
beyond those focused exclusively on human genetics, we have substantially accelerated our outreach
progress over the past year and have brought in multiple new investigators through the small pilot,
RCDC, and Pilot mechanisms. These investigators have actively utilized our frail animal model
resources and have enabled us to expand more broadly into mitochondrial biology and epigenetics.
Many important new studies related to the renin-angiotensin system have been supported by the RCDC
and Pilot Cores, and supported investigators have utilized RC-2 human and supply resources to move
their areas of science ahead. The following summary details the relevance of the accomplishments to
the overall mission of this OAIC, and how the science has shaped the evolving scientific agenda of
RC-2 and the entire OAIC, and how RC-2 leaders and supported investigators interact with those from
the RC-1, pilot, and RCDC cores. These activities have certainly allowed us to maintain and expand
very high levels of visibility and leadership across the Medical Center and the University, and rather
than organizing the following section by specific aims, we have outlined the scientific
accomplishments that RC-2 supported over the past year by topics, beginning first with Human
Genetics, followed by epigenetics and mitochondrial focused projects. We will also describe the
ongoing efforts to support the molecular parts of investigators supported by RCDC and Pilot projects
using animal and molecular resources. Details of the scientific accomplishments of these RC-2
supported investigators are more fully articulated in RCDC and Pilot sections of this progress report.
Human Genetics Projects: A major goal of the first 5 years of our OAIC was to play a leading role
in genetic discovery in frailty, and RC-2 continues to play a major local and national role in the
development of genetic analyses related to frailty. We have continued to support multiple external
projects and work to develop the most rigorous phenotypes related to frailty and late-life decline. The
development of these phenotypes take place as a part of our bimonthly RC-2 meetings attended by RC2 core leadership and supported staff, supported investigators, and RC-1 leader Qian-li Xue. In
addition, we continue to lead aging and frailty related efforts in large consortiums with genome wide
and candidate gene genotypes available for analysis by participating investigators. RC-2 investigators
have been able to play leading roles in the development of a number of major aging and frailty
phenotypes as described below.
Skeletal Muscle/Strength Endophenotype (R-01 supported external project): (Brock Beamer,
MD, Qian-Li Xue, PhD). In last year’s report, we reported the development of a longitudinal
phenotype in the Women’s Health and Aging Studies, and found that the longitudinal rate of decline in
grip strength was more predictive of adverse outcomes (e.g. falls and severe walking limitation) than
was the measure of grip strength itself. That is, “being very weak” is not as predictive as “getting
weaker”. Building on this work, we recently performed longitudinal analyses to assess the prognostic
value of strength decline in different muscle groups on the risk of all-cause mortality. We hypothesized
that strength may decline at different rates, contemporaneously or not, for different muscle groups due
to factors such as “local” diseases affecting specific musculoskeletal regions, differences in amount of
muscle tissue/muscle mass, absolute strength at baseline, and frequency and intensity of use.
Therefore, it is important to assess the correlations among individual-level changes in grip, knee, and
hip strength over time and their relative predictive ability for all-cause mortality in older adults. We
found that the rate of change varies across muscle groups and the rate of change in grip strength was
not correlated with those of knee and hip strength. Faster rates of decline in grip and hip strength, but
not knee strength, were independently associated with elevated risk of mortality after accounting for
their baseline levels and potential confounders. These findings suggest that monitoring the rate of
decline in grip and hip flexion strength in addition to the actual levels may greatly improve the
identification of women most at risk of dying.
Xue Q-L, Walston JD, Fried LP, Beamer BA. Rate of decline in grip strength predicts the risk of
falling, physical disability, and frailty: The Women’s Health and Aging Study. Arch Intern Med. 2011;
in press.
Skeletal Muscle Candidate Gene Study (R-01 supported external project): (Brock Beamer, MD,
Amy Matteini PhD). RC-2 has continued to provide intellectual and analytical support to the further
development of Dr. Beamer’s R-01 through the development of an association study that connects
muscle related candidate gene SNPs and the phenotypes previously developed in this core using the
Health ABC population. A manuscript is under development.
Long Life Family Study Endophenotype Development (U-01 supported external project):, Amy
Matteini, PhD, Jeremy Walston, MD): Exceptional longevity is often characterized as robustness or
lack of frailty and has shown to be highly heritable. Genetic epidemiologist and research associate
Amy Matteini PhD, along with guidance from core co-director and genetic epidemiologist Dani Fallin
and PI. Jeremy Walston, continue to lead developmental efforts with colleagues from the Long Life
Family Study (LLFS) This NIA-funded family-based cohort study was developed to identify
phenotypic and genotypic variation that correlates with long and healthy life. The data presented last
year in this report has now been published. . This grant was renewed in 2010 and Drs. Matteini and
Walston are actively participating in the development of relevant phenotypes related to aging, frailty
and longevity in this population with special focus on pulmonary phenotypes, skeletal muscle
phenotypes, inflammatory marker phenotypes, and telomere length related phenotypes. These
phenotypes, once developed, will be moved into GWAS analyses within this population in order to
determine what if any genetic influence contributes to a long and healthy life. Hence, RC-2 continues
to provide critical insights into phenotype development, and regarding biologically relevant pathways
to these investigators.
Matteini AM, Fallin MD, Kammerer CM, Schupf N, Yashin AI, Christensen K, Arbeev KG, Barr G,
Mayeux R, Newman AB, Walston JD. Heritability estimates of endophenotypes of long and health
life: the Long Life Family Study. J Gerontol A Biol Sci Med Sci. 2010 Dec;65(12):1375-9..PMID:
20813793
Assessment of Mitochondrial DNA variation in Frailty, (Pilot Core supported project) (Dan
Arking, PhD, project leader, Zenobia Moore, PhD candidate). Alterations in mitochondrial DNA
and declines in energy level have long been hypothesized to underlie molecular and physiologic
declines in function in older adults. In order to explore genetic hypotheses related to frailty, RC-2
support continues to be utilized to develop Dr. Arking’s successful pilot study application for
genotyping of mitochondrial DNA in a case-control pilot study of frail and non-frail older adults from
the Cardiovascular Health Study (CHS). Data reported in this section last year has now resulted in a
Plos 1 publication listed below. It has also facilitated the further development of Zenobia Moore’s
PhD thesis project development that will utilize SNPs related to mitochondria and muscle biology that
have previously been generated in multiple CHS studies in order to determine the relationship between
them, frailty, and the development of muscle weakness and disability in this population.
Moore AZ, Biggs ML, Matteini AM, O’Connor A, McGuire S, Beamer B, Fallin MD, Fried LP, Walston
J, Chakravarti A, Arking DE. Polymorphisms in the mitochondrial DNA control region and frailty in
older adults. (PLoS One. 2010 Jun 10;5(6):e11069.PMID: 20548781
Genetic Influence on Inflammation and Frailty and Adverse Outcomes in Older Adults (R-01
supported external project) Amy Matteini, Dani Fallin, Ravi Varadhan, Karen Bandeen-Roche,
Jeremy Walston. The goal of this study is to identify genes or gene pathways that may allow us to
determine biological pathways that may be operant in frailty. Prior work in this OAIC has identified
serum markers of inflammation (IL-6, CRP) as highly associated with frailty and other adverse
outcomes.
Inflammatory Phenotype: We hypothesized that aggregate measures of serum cytokines would be
even more predictive of frailty and adverse outcomes, and that aggregate phenotypes could be utilized
to identify genetic variants that predict late-life inflammation, frailty, and adverse outcomes.
Substantial progress has been made in the past year in the development of both the aggregate
inflammatory phenotype and in genetic analyses that connect relevant candidate genotypes to this
phenotype and to frailty. We first studied 18 cytokines in the In CHIANTI population, and identified
CRP, TNF-alpha receptor 1, IL-6, IL-18, and IL1-RA as the most correlated with age and mortality.
We then measured these 5 cytokines in the much larger Cardiovascular Health Study (CHS) and
developed 3 aggregate phenotypes using these measures (Weighted Summary Score, Principal
Components Score, and Mortality Score). These were developed in collaboration with the RC-1
faculty. MRS score that consisted of IL-6 and TNFR1 was found to perform better than the other
aggregate and individual measurement for predicting 10 year mortality. Manuscript is in preparation
for this analysis.
Inflammatory Genotype: Initial analyses of a candidate gene panel supported by Dr. Walston’s R01
has been performed using individual cytokines IL-6 and TNF-alpha R1 as the dependent variable.
Initial results are listed in tables 2 and 3 below, with bold gene symbols being ones that have
previously associated with muscle strength or frailty in prior genetic studies. Further analyses are
ongoing in this cohort, as well as validation studies. Although this data is not conclusive, and
additional analyses need to be performed, they suggest that there may be some common biological
pathways represented by genes such as DNMT3A and 3B, WNT 5B, CREBBP, PAX 3 and PAX 7
that have demonstrated positive associations with either frailty or related endophenotypes of
inflammation or skeletal muscle weakness. Interestingly, the DNMT family of genes are important in
DNA methylation, and the WNT and PAX families are important in muscle homeostatsis, and
CREBBP is important in gene transcription and apoptosis. Several manuscripts for this work are
presently under preparation, and integration with the epigenetic development project are also
underway.
Developmental Project of Candidate Genes in Frailty Research (OAIC Developmental Project,
External Project for Women’s Health and Aging Study). Yen-Yi Ho, Aravinda Chakravarti, Dani
Fallin, Dan Arking. This project was initiated during the first 5 year funding period of the Hopkins
OAIC and allowed RC-2 to develop the human and analytical infrastructure to develop and validate the
frailty phenotype and explore relevant biological pathways that were hypothesized to influence the
development of frailty and late-life decline. We first explored this phenotype in the Caucasian subset
of the Women’s Health and Aging Studies I and II. This paper was accepted for publication in 2011
and is presently in press. Although no single-nucleartide polymorphism reached study=wide
significance after controlling for family-wise false –discovery rate at 0.05, SNPs within the 5methyltetrahydrofolate-homocysteine methyltransferase (MTR), caspase 8 (CASP8), CREB-binding
protein (CREBBP), lysine acetyltransferase 2B( KAT2b), and beta-transducin repeat containing
(BTCR) loci were among those most strongly associated with frailty. Several of these genes have been
moved into other candidate gene studies in order to determine if these findings can be validated, and if
these apoptotic and transcription regulation related pathways may be operant in the development of
frailty.
Ho Yen-Yi, Matteini AM, Beamer B, Friend L, Xue Q, Arking D, Chakravarti A, Fallin MD, and
Walston J, Exploring Biologically Relevant Pathways in Frailty, In Press, Journal of Gerontology:
Medical Sciences, Accepted March 2, 2011.
Ongoing Frailty Analysis in CHS: Building on the RC-2 analytical and phenotype development
infrastructure, and from the Externally supported project listed above, we performed an analysis
utilizing 1500 SNPs from candidate genes determined in the first 5 years of the OAIC as potentially
relevant to frailty. These genes were determined through careful consideration of biological processes
that are hypothesized to influence frailty, from mouse muscle differential gene expression studies,
through human studies of declining skeletal muscle, and by using candidates from inflammatory
pathway activation genes. A cross-sectional association analyses was performed using multinomial
logistic regression models for 3-level categorized frailty, and general linear model for the continuous
dependent variables - grip strength and walking speed; Explanatory variables are age, sex, weight and
height; SNPs are coded as additive genetic model. All analyses are stratified by race. The genes with
suggestive associations include those in skeletal muscle maintenance pathways and those in
inflammatory pathways. Validation of these results in other populations is underway. Given our
success in identifying that longitudinal grip strength measurements were far more predictive of adverse
outcomes than any other similar variable, we are now developing a longitudinal analysis of frailty in
this same population. In the generalized linear mixed model, random effects would be intercept and
time, and adjusted by baseline age, BMI, lean body mass, time and gender. In the coming weeks, an
association analysis between longitudinal frailty and candidate SNPs with an additive model, stratified
by race will be conducted and a manuscript will be developed to present these results. Preliminary
results are displayed below. The highlighted genes were found to have significant associations in both
populations. The biological pathways that each of these represent will be targeted for further
developmental efforts within RC-2.
Table 2: CHS_time to frail, African American group
race Marker
gene
Chr maf
coeff
p
AA rs13036246
2
0.356
0.37 1.1E-04
DNMT3A
AA rs10906776
SUV39H2
10
0.209
0.30 1.7E-03
AA rs1246411
AREG
4
0.471
-0.27 2.0E-03
AA rs17745484
2
0.103
0.47 3.7E-03
DNMT3A
AA rs11489282
CYCS
7
0.368
-0.25 3.9E-03
AA rs12424889
WNT5B
12
0.154
-0.32 5.3E-03
AA rs1691274
AREG
4
0.358
-0.25 5.5E-03
AA rs7594723
PCBP1
2
0.077
0.41 5.9E-03
AA rs13334803
CREBBP
16
0.123
0.37 5.9E-03
AA rs2294512
DIO1
1
0.492
0.23 6.1E-03
AA rs1978859
2
0.132
0.36 6.6E-03
PAX3
AA rs2717885
CYCS
7
0.484
-0.22 7.5E-03
AA rs1190626
RIN1
11
0.253
0.26 8.9E-03
Table 3: CHS_time to frail, Caucasian group
CA rs10489153
PAX7
1
CA rs1835432
2
PAX3
CA rs551027
PAX7
1
CA rs283882
REG1A
2
CA rs1131171
NCL
2
CA rs2019203
PCGF2
17
CA rs7590760
2
DNMT3A
CA rs3791031
PAX7
1
CA rs7608595
PAX3
2
CA rs1367416
PAX3
2
CA rs12134434
WNT4
1
CA rs13077668
WNT7A
3
CA rs2289093
DNMT3A
2
CA rs7586294
DNMT3A
2
CA rs4674641
PAX3
2
0.023
0.388
0.116
0.055
0.186
0.474
0.452
0.098
0.446
0.139
0.032
0.354
0.245
0.454
0.21
-0.42
-0.13
-0.21
-0.25
-0.14
-0.11
-0.12
-0.18
-0.11
-0.17
0.28
0.12
-0.13
0.11
0.13
4.2E-03
5.4E-03
7.6E-03
1.1E-02
1.4E-02
1.4E-02
1.4E-02
1.4E-02
1.7E-02
1.7E-02
1.8E-02
1.9E-02
2.0E-02
2.3E-02
2.4E-02
Consortium Building Around Genetic Studies of Frailty and Aging: A major goal of the RC-2 is
to develop infrastructure that will greatly facilitate the development of genetic studies related to frailty
and frailty related endophenotypes. During bi-weekly RC-2 leadership meetings, we have continued to
provide scientific direction to each other and to a number of investigators around the country who are
interested in developing novel phenotypes and genetic analyses. Faculty members and trainees
affiliated with RC-2 have continued to benefit from productive, ongoing collaborative relationships
with investigators who participate in the Women’s Health and Aging Study, the Cardiovascular Health
Study, In CHIANTI, and Baltimore Longitudinal Study on Aging, Health and Body Composition
Study (Health ABC), and with the Long Life Family Study (LLFS). In addition, members of RC-2 are
now on the Aging subcommittee of the Cohorts for Heart and Aging Research in Genetic
Epidemiology (CHARGE) consortium and the CARE consortium. CHARGE represents
approximately 10 cohort studies from around the world with finished GWAS platforms and with aging
related data. CARE has over 20K of candidate gene SNPS related to inflammation and cardiovascular
disease that can be utilized to explore genetic hypotheses. These collaborations have given RC-2
supported investigators and their trainees outstanding opportunities to develop genetic analyses related
to frailty and aging over the past year. An additional important example of ongoing developmental
efforts include the collaborative development of an R-03 between Frank Lin, MD, an RCDC supported
investigators with focus on age-related hearing loss and Amy Matteini, PhD, a research associate and
mentee of Dr. Fallin and Dr. Walston. They are developing a genetic analysis that builds on Dr. Lin’s
expertise in the hearing loss phenotype, and Dr. Matteini’s expertise in consortium building and
GWAS analyses. Such an analysis has never been done before, and demonstrates the unique abilities of
our OAIC RC-2 to connect across disciplines to develop new science that may help to explain the
pathophysiology of late life hearing decline. More details of this RC-2 supported project will be
reported in next year’s progress report.
Genome-wide Association Study of Grip Strength (Amy Matteini, PhD, RC-2 supported project): In
collaboration with the Cohorts for Heart and Aging Research in Genetic Epidemiology (CHARGE)
consortium research associate Amy Matteini (working with Dani Fallin and Jeremy Walston) have
developed and led analysis of the cross-sectional association between maximal grip strength and 2.1
million single nucleotide polymorphisms (SNPs) utilized in this GWAS study. Data from twelve
prospective cohorts were used in this analysis. Main effects were estimated using multiple linear
regression models, adjusted for age, gender, weight and height. Additional models were built to test
for SNP by gender and SNP by age interactions. Inverse variance weighted meta-analysis will be
performed for a fixed effects model of beta and standard errors from all studies. A threshold of 5x10-8
will be used to determine genome-wide significance. A related GWAS study was performed in
parallel by colleagues in the CHARGE consortium evaluating lower extremity strength in eight cohorts
of older adults. Preliminary results of marginal models of both grip and lower extremity strength did
not yield any hits of genome-wide significance. A bivariate meta-analysis is currently being
performed to test for common significant signals between the strength outcomes. This analysis should
be completed by 5/15/11. There are four additional cohorts of older adults that are interested in
serving as replication datasets for any strength signals that are localized via the bivariate model. These
studies are available this spring. Lastly, we are exploring longitudinal strength models in the
CHARGE consortium. Although the sample size will be smaller than the cross-sectional analyses,
trajectories of decline may be a more precise phenotype that lends itself to genetic association tests.
This analysis should be completed by fall, 2011.
Epigenetic Development: A major effort was undertaken in the past 2 years to integrate epigenetic
measurements and expertise into RC-2. These ongoing collaborations will likely facilitate the
development of multiple new studies and help train new aging focused investigators in the coming
year.
RC-2 Development Project, Year 6 and 7: Development of a “Frailty/Aging” methylation panel
for affordable high-throughput methylation studies related to frailty (RC-2 Development
Project; Andrew Feinberg and M. Daniele Fallin, Co-PI): Epigenetic mechanisms such as
methylation may be very important in human disease, especially for diseases of older age such as
frailty, given the potential for change in epigenetic marks with age. Yet, methylation has not been
widely studied with respect to age-related diseases beyond cancers. One main obstacle has been the
availability of measurement technology that can quantify methylation locally, or across the genome, in
a large number of samples for a reasonable price and within a reasonable timeframe. To date, the
investigators have completed the first aim of the development project which was to perform whole
genome site-specific methylation, using whole-genome methylation arrays (WGM), on 50 extremely
frail and 50 extremely not-frail participants of the BLSA, chosen based on aggregate methylation
results, and matched by age, sex, and comorbidity.
These investigators using for high-throughput methylation analysis in partnership with the Johns
Hopkins Center for Excellence in Genomics (CEGS), (Feinberg, PI). The developmental wholegenome methylation arrays were performed on a small set of 100 BLSA participants chosen to be at
the extremes of frailty (50 extremely frail, 50 non-frail). 8 regions that showed differential
methylation (DMRs) in CHARM assays were investigated by pyrosequencing. The list of genes near
these regions are: KIAA1414, TIMM17A, ALDH6A1, USP53/MYOZ2, PRCP, PUNC, PPP3CA,
PRKG1. These initial results did not validate with this method, and with subsequent Sanger
sequencing methodology and with non-CpG Island DMR Pyrosequencing. Ongoing efforts to trouble
shoot through methodology continues at present.
These investigators have carefully considered all of these data, and have suggested multiple possible
explanations for this failure of validation in this development project. What distinguishes these
CHARM data from all others is that DMRs are found at high frequency in islands. However, validation
has not been successful. This may be due to normalization probes designed for lower density CpG, and
center biostatistians are working on normalization methodology. There may also be some global
difference in DNA methylation, and this would be consistent with what studies that were done last year
with the frail mouse model. In that case, the CHARM assays have a hard time picking up individual
differences because of normalization. Our plan then is to do LUMA on frail vs. non-frail. There are
hidden signals behind the island findings, i.e. lower on the DMR list. Investigations of these low
probability hits are underway. The result was negative. So it may be that frailty is unrelated to DNA
methylation, or the study is underpowered to reveal gene-specific differences in this complex
undoubtedly heterogeneous phenotype. We are very eager to look at inflammatory markers, as they
make the most sense epigenetically given the source of measurement (blood) and given the
science.
If the findings listed above are validated, they will then be utilized for the second specific aim, which
is to develop a final list of 1536 sites (approximately 300 genes) to populate a “frailty/aging” custom
methylation panel. Given initial delays in the ability to obtain IRB approval for the methylation project
in Aim 1, and subsequent delays related to validation experiments on the original CHARM assay
findings, we have extended support for this developmental project into the present academic and grant
year. We will continue to supply support as is necessary to complete this developmental aim. The
RC-2 and LAC leadership believes that this is potentially a very important area of investigation, and
one that may well lead to broader understanding of the biology that underlies late-life decline.
Additional interactions around the mouse model of frailty and recent human genetics findings are
helping the RC-2 leadership develop a broader and integrated picture of inflammation, human genetics,
and epigenetic changes that result in late-life decline.
Mouse Model of Frailty and the Development of other Relevant Animal Models. RC-2 has
continued to provide support to many investigators in the other cores for animal model development as
specified in SA4.
During the first years of OAIC funded frailty research, it became evident that an animal model for
frailty would be critical to further study molecular pathways highlighted by genetic research, and to
facilitate the development of interventions. Using RC-2 support, investigators from the Biology of
Frailty Program in the Division of Geriatric Medicine identified the IL-10-/- mouse as the highest
priority for further development based on evidence that demonstrates a) a significantly accelerated
decline in strength over time as well as activity declines compared to age and gender matched
background strains that begins later in life b) significantly increased serum IL-6 levels in older age
groups, similar to that seen in frail humans and c) altered gene expression in older IL-10-/- mice
compared to control strains that suggest that mitochondrial related proteins and apoptosis may be an
important link between the activation of inflammation late in life and the declines in muscle strength
that are a core feature of frailty (Walston J et al, Journal of Gerontology, 2008). Subsequent to this
study, the OAIC has supported several smaller pilot studies that have utilized this mouse model
through the provision of mice and measurement expertise for studies of anemia of inflammation
(Cindy Roy, RCDC supported investigator), cardiac function (Lil Barouch, Small Pilot), pulmonary
function (Enid Neptune, Pilot Core, Franco D’Allesio small pilot), Amy Unterman, PhD candidate
working on epigenetic project with frail mouse. From this work, several abstracts have been
submitted in the past year, including one submitted to the American Heart Association meetings by Dr.
Barouch and collegues that highlights smooth muscle related differences between frail mouse and
control mice in aortic rings. This data is now being developed into a manuscript.
Fred Ko, MD, now a Geriatrician on faculty at the Mt. Sinai University School of Medicine, in
collaboration with Dr. Walston, is continuing to develop the Frail mouse model by further
characterizing the inflammatory and endocrine and mortality profile. Two manuscripts have been
developed related to Dr. Ko’s work, including one to be published in AGE and one under review for
Aging Cell.
Ko F, Yu Q, Xue QL, Yao W, Brayton C, Yang H, Fedarko N, Walston J. Inflammation and mortality in
a frail mouse model. Age (Dordr). 2011 Jun 2. [Epub ahead of print] PMID: 21633802.
Year 8 RC-2 Development Project: Jiou Wang, PhD, Assistant Professor of Biochemistry and
Molecular Biology. “Identifying Molecular Biomarkers and Genetic Modifiers of Frailty in
Caenorhabditis elegans Models”
Project Overview / Specific Aims
Frailty is increasingly recognized as a clinical condition with a biological basis. The phenotypes of
frailty are thought to represent combinations of the following symptoms: weakness, fatigue, weight
loss, slow walking speed, low levels of physical activity, and mild cognitive changes. Frailty is highly
prevalent in the elderly but the mechanisms through which aging might affect the frailty syndrome
remain unknown. Dr. Jiou Wang and colleagues seek to understand the common molecular basis
underlying degenerative diseases and aging-dependent frailty. Their hypothesis is that during the
development of frailty there are predictable molecular events that can be monitored by specific
biomarkers and that these molecular events partially overlap with molecular cascades that lead to the
tissue decline in normal aging or degenerative diseases. If this hypothesis is true, they can apply what
is learned from particular degenerative diseases to understand and treat conditions of the multisystemic
decline in the frailty syndrome. Much of the current understanding of degenerative diseases, including
neurodegeneration, comes from studies using animal models. One example is Amyotrophic Lateral
Sclerosis (ALS), which is the major form of motor neuron degenerative disease. Discoveries of genetic
mutations in a subset of ALS patients have opened doors for engineering genetically modified animals
models and accelerated our understanding of the molecular mechanism of the disease. Recently, to
overcome the limitation of the mouse model in its adaptability to largescale screening, Dr. Wang
created an invertebrate model of ALS in C. elegans, a model organism that is also widely used for
studying aging. The C. elegans model of ALS developed robust phenotypes mimicking the human
disease, including pronounced movement defects and protein aggregation, and studies using this C.
elegans model have revealed promising genetic modifiers of disease that we recently find operating
similarly in mammalian systems. Here, Dr. Wang proposes to systematically study aging-related frailty
using C. elegans as a model organism. The advantages of this model organism include its short
lifespan, transparency, and powerful molecular tools. Furthermore, the studies of aging dependent
degenerative diseases in C. elegans provided tools and candidate genes to explore genetic modifiers of
the frailty phenotypes in normally aged C. elegans and the underlying age-dependent molecular basis.
This exploration provides insight into conserved molecular underpinnings in human frailty. The
specific aims are as follows: Specific Aim 1: To identify molecular markers for the frailty phenotypes
in C. elegans, such as sarcopenia, by examining synaptic neurotransmission and mitochondrial
integrity.
Specific Aim 2: To identify genetic modifiers of the frailty phenotypes in C. elegans by examining
candidate genes involved in aging and degenerative diseases.
Progress Summary
Dr. Wang and colleagues have established of a new C. elegans model of age-depedend
neurodegeneration that is linked to TAR DNA-binding protein 43 (TDP-43). TDP-43 plays a key role
in the neurodegenerative diseases including amyotrophic lateral sclerosis and frontotemporal lobar
degeneration. The C. elegans models developed severe locomotor defects associated with the
aggregation of TDP-43 in neurons. Importantly, the TDP-43 C. elegans model exhibit age-dependent
decline in its phenotype including a worsening locomotor defect. Towards the Specific Aim 1 of the
OAIC project, they found that TDP-43 demonstrated an unusually high tendency to aggregate, a
property intrinsic to the wild-type protein. Distinct disulfidelinked TDP-43 dimers and oligomers were
detected. In C. elegans, the toxicity and protein aggregation of TDP-43 were regulated by
environmental temperature and heat shock transcriptional factor 1, indicating that a deficiency in
protein quality control is a risk factor for TDP-43 proteinopathy. Furthermore, they have found that
synaptic defects at the neuromuscular junctions are underlying the locomotor defects in the TDP-43 C.
elegans models. Towards the Specific Aim 2, the investigators found that the toxicity and protein
aggregation of TDP-43 can be significantly attenuated by a deficiency in the insulin/ insulin-like
growth factor 1 (IGF-1) signaling in C. elegans and mammalian cells. These results established a direct
link between the aging program and the toxicity and aggregation of TDP-43.
The investigators have identified candidate genes that suppress protein aggregation and expand
lifespan in C. elegans. They will focus our effects on validating and charactering the candidate genes
in the remainder of the project. They will continue to meet regularly with the RC-2 and LAC
leadership to identify ways to integrate these findings into human and/or animal models studies.
Publications Progress / Abstracts / Presentations /Grant Development
The progress summarized above has been published in the latest issue of Human Molecular Genetics.
Zhang T, Mullane PC, Periz G, Wang J. TDP-43 Neurotoxicity and Protein Aggregation Modulated by
Heat Shock Factor and Insulin/IGF-1 Signaling. Hum Mol Genet 2011;doi: 101093/hmg/ddr076.
They have also presented this work as a poster entitled “Aging Pathways modulate TDP-43 Protein
Aggregation and Neurotoxicity” at the 2011 Pepper OAIC Annual Meeting at Bethesda, Maryland.
Mitochondrial Biology and Oxidative Stress Measurements in Frailty Research: A component of
the infrastructure that we have aimed to provide to OAIC supported investigators and to the JHU aging
research community was to be focused on mitochondrial biology and oxidative stress measurement.
Over the past year, we have identified and begun to work very closely with two individuals who have
considerable expertise in this field. RCDC supported scholar Peter Abadir and OAIC PI Dr. Walston
have established ongoing collaborations with Dr. Brian O’Rourke and Dr. Robert Weiss from the
Division of Cardiology at Johns Hopkins. Dr. O’ Rourke, of the Division of Molecular Cardiology
brings basic molecular measurement expertise including mitochondrial respiration, bioenergetics,
ultrapurification, nitric oxide and other free radical measurement in mitochondria. He will continue to
provide human and infrastructural resources to OAIC investigators. Dr. Weiss brings considerable and
unique expertise in whole organism MR spectroscopy that enables the measurement of whole animal
ATP production. This has led to the support of a number of pilot projects related to the aging renin
angiotensin system, and to a frail mouse development project as part of ongoing collaborations. At
least two R-01 and one R-21 grants are under development based on work that was performed as part
of the OAIC and will be more fully reported on in next year’s report.
RC-2 Interactions with Other Cores and with Supported Faculty and Additional Molecular
Expertise Provided to OAIC Scholars: In addition to the projects listed above, present or past
OAIC supported scholars Sean Leng and George Wang have received molecular support for
performance of assays related to their ongoing immune system studies related to frailty and
immunosenescence (see Pilot and RCDC sections). Ronni Cohn and Sevil Yasar, Tyesha Burks, and
Peter Abadir, supported by Pilot, Diversity supplement, and RCDC respectively, have received
ongoing advice and molecular support for their projects related to the Renin-angiotensin System. This
is a rapidly expanding area within our OAIC and is a system that helps to explain connections between
energy production, mitochondria, and inflammation and frailty.
Increasing Visibility of the Hopkins OAIC from RC-2 supported projects: Our RC-2 supported
investigators have continued to thrive academically and hence have helped to improve the overall
institutional and national visibility of this OAIC with the awarding of 3 K-23 awards to its RCDC
scholars (Abadir, Lin, and Wang) in the past year. These awards, along with the important areas of
frailty science that each of these investigators have worked on, and their recent publications have
shown the spotlight on our training and scientific initiative across the Johns Hopkins Medical
Institutions. As a result of these awards and related publications, entirely new areas of frailty related
science are emerging and new investigators are being recruited to work on frailty related issues in
hearing loss, CMV related immunoscenence, and the aging renin-angiotensin system. Tyesha Burks
and Ronald Cohn have a manuscript derived from OAIC supported work (Pilot and Diversity
supplement) that has resulted in an ‘in press’ paper for Science Translation (results embargoed until
publication). This manuscript will certainly provide very high visibility at JHU and across the country
for the quality of our basic and translational investigations into frailty and late-life decline.
II.C. RESEARCH CAREER DEVELOPMENT CORE (RCDC)
Gary Gerstenblith, M.D., Core Leader
410-955-6835
410-614-9422 FAX
[email protected]
Paulo Chaves, M.D., Ph.D., Clinical Translation Unit Director
410-614-0740
410-614-9625 FAX
[email protected]
The purpose and function of the Research Career Development Core (RCDC) of the Johns Hopkins
OAIC are to identify, attract, select, and to provide training, mentoring and translational research skills
for junior faculty who will become leaders in the development and implementation of research in the
field of frailty and interventions that preserve independence for older adults. It emphasizes the
development of skills required to apply basic research findings to clinical investigation and
interventions, translate clinical findings into mechanistic studies, and disseminate the results of clinical
investigation to the health provider and broader community, with the aim of decreasing the likelihood
for the development of frailty and improving clinical outcomes for frail older adults. Consonant with
this purpose, the specific aims of the RCDC are to continue to contribute to the Hopkins OAIC’s
overall goals by:
1. Research career development for frailty investigation: Promoting the development of future
research leaders in frailty research. To that end, we attract, select, and provide to outstanding junior
faculty the protected time and the career development, mentoring, and didactic skills essential to their
growth into independent investigators. These skills enable them to:
a. Understand and translate advances in basic science research on frailty and integrate them
with clinical needs so as to provide unique insights and understandings of strategies to prevent
and/or treat frailty and thus maintain and restore health and independence of older Americans.
b. Develop, design, test and evaluate clinical research interventions to prevent and treat frailty
associated with aging and its complications.
c. Develop abilities essential for academic career advancement, including written and oral
communication, grant development, time management, explicit goal setting, and collaboration.
d. Successfully bridge the critical period between fellowship and independent funding for
investigator-initiated research and those supported to become independent investigators in
frailty research and translation.
2. Infrastructure: Provide the environment, structure, intellectual input and guidance, and critical mass
of investigators that are needed to ensure successful basic and clinical multidisciplinary research
collaboration among the supported faculty so as to accelerate the development and translation of
breakthroughs in the prevention and treatment of frailty. This includes the leadership of a Clinical
Translation Unit, in collaboration with other Cores, which focuses on investigator training and
mentorship in clinical research; assistance with IRB, legal, and ethical issues, data collection and
protocol tracking. It includes a registry of frail and non-frail older individuals; biostatistical, technical
and laboratory support; and space to aid RCDC and pilot Core faculty in the conduct of clinical trials
designed to identify and assess the effect of interventions. This unit incorporates contributions from all
Cores in order to provide an effective, multidisciplinary resource to our investigators. Updates on the
progress of the CTU are provided below.
3. Diversity: Continue to achieve full and equitable representation and inclusion of women and
minorities among OAIC RCDC faculty.
4. Leadership: Work with the Leadership and Administrative Core to establish scientific goals and
coordinate activities with other Cores and Core leaders to evaluate the strengths and limitations of the
program and to appropriately revise the goals and processes, as needed, to optimize the careers of
academic junior faculty in the field of frailty research.
5. Productivity: To establish and monitor productivity and accountability benchmarks and to support
RCDC faculty in achieving them.
6. Monitoring: Provide coordination, oversight, and reporting of all RCDC-supported activities. In the
reporting function, we also endeavor to highlight the accomplishments of the RCDC faculty and
increase the visibility of the RCDC so as to increase the attractiveness of this career path for potential
faculty.
Clinical Translation Unit :
Introduction
In preparation for the conduct of frailty-related intervention studies, we recognized the value of
creating a unit broadly aimed at aiding investigators in the design, recruitment, and implementation of
clinical trials. This Clinical Translation Unit (CTU) is located on the Bayview Medical Campus, which
is the primary focus of the Division’s clinical activities. The CTU is directed by Dr. Paulo Chaves,
who has extensive geriatric and clinical epidemiology expertise, and Dr. Gary Gerstenblith, who
provides senior mentorship and contributes knowledge concerning the design of translational research
studies. There is also extensive expertise provided by RC-1 and RC-2, and input from Dr. Kay
Dickersin, on the leadership council of the LAC. Dr. Dickersin directs the Center for Clinical Trials at
the Johns Hopkins Bloomberg School of Public Health. In addition to “intellectual capital”, the CTU
provides infrastructure elements common to intervention frailty studies, including a research assistant
trained in the assessment of physical and cognitive frailty, information technology, and nursing
personnel. Additional clinical coordinators are also trained in these areas and are able to assist OAIC
funded investigators if their clinical recruitment needs overlap with other studies.
Frailty Registry
Background: In view of the challenges of enrolling older study subjects in clinical trials, particularly
those who are frail and pre-frail, the CTU established a registry of patients to assist in recruitment and
enrollment efforts. To that end, we obtained IRB approval for the project, entitled “A Registry of Older
Adults Who May Be Willing to Participate in Research (IRB# NA_00013162).” This registry is
composed of patients cared for in outpatient geriatric clinics and who are willing to consider
participation in clinical translational studies. The Beacham ambulatory care clinic at Bayview Medical
Center has served as the main recruitment venue for registry-related enrollment and screening.
Recruitment has also included the General Internal Medicine Outpatient clinic also at the Bayview
Medical campus. Patients coming to the clinic are approached by the research coordinator and the
purpose of the Registry is explained, the consent form presented and their willingness to participate in
aging-related translational research studies assessed. If they agree to participate and sign the consent
form, patients undergo our frailty screening protocol without interrupting clinic flow. The frailty
screening includes assessment of physical activity levels, fatigue symptoms, and weight loss, as well as
usual walking speed over a 4-meter course and grip strength. Further data, including past medical
history and laboratory results are systematically abstracted from their medical records. Led by the
OAIC Biostatistics Core, a network-based registry database was created to store data and enable data
base inquiries. Many supported investigators have utilized this expanding resource, including Drs.
Dobrosielski, Wang, Abadir, Argawal, Leng, Boyd and Pustavoitau.
Update: Since starting of the project, a total of 968 patients have been approached. Of these, 415 have
consented and evaluated/enrolled into the registry.
CTU-Related Intervention Studies
PACTTE: Partnership for Anemia Clinical and Translational Trials in the Elderly (U01)
Background: The NIA recently released an RFA entitled, “Partnership for Anemia Clinical and
Translational Trials in the Elderly.” A group of investigators from across the country developed a
consortium in order to respond to this. Given that the focus of this RFA is the treatment of anemia of
unclear etiology in older adults, and that functional and cognitive outcomes are deemed important
outcome measures of any proposed interventions, the OAIC-sponsored CTU faculty Dr. Chaves,
RCDC-supported faculty Dr. Roy, and OAIC-PI Dr. Walston were involved from the very beginning
in the development of the scientific and recruitment planning for this. In the Hopkins subcontract
application, CTU housed personnel would be hired to recruit older subjects with anemia of unclear
etiology would be recruited from the clinics where the CTU is active. They would be treated with
interventions as determined by the core group of study leaders after funding, either at Johns Hopkins or
at the nearby NIA clinical investigations unit at Harbor Hospital. This recruiter would interact
closely with CTU faculty and staff, and potentially access frail, older adults who have consented to be
part of the frailty registry as described above. In addition to the recruitment component, RCDC
supported investigator Cindy Roy was instrumental in the design of the basic biological samples that
are proposed to be stored for future use if the grant is funded. She has developed a great interest in
clinical translational research as part of this effort, and will apply for additional funding to perform
these measurements if the U-01 is funded. This will build on RC-2 and RCDC support of Dr. Roy, and
will allow her to develop human subject research skills in the coming months to years.
Update: The protocol for the first study, which will involve an IV iron intervention, has been finalized,
IRB approval has been obtained, and this pilot is its final preparatory stages for field implementation.
Bi-Weekly Conference Calls are taking place. Dr, Walston is the Johns Hopkins PI for this project, and
a member of the Steering Committee. Dr. Chaves is a member of the Functional Outcomes
Subcommittee. Dr. Roy is a member of the Translational Subcommittee.
Pilot trial on vitamin D and functional decline in pre-frail older adults
Background: Building on developmental work reported in the previous period, Dr. Chaves and
colleagues from the LAC (Drs. Walston, Gerstenblith, Bandeen-Roche) developed a pilot intervention
study to explore the impact of vitamin D supplementation in pre-frail individuals with insufficient
vitamin D levels on physical and cognitive function outcomes. Preliminary data used in the
development of this trial involved secondary data analysis done in the Women’s Health and Aging
Studies I and II data base, which revealed a high prevalence of vitamin D insufficiency, and a strong
and independent association of low vitamin D levels with prevalence and incident frailty in
community-dwelling older women. These data were presented at the 2009 American Geriatrics Society
Annual Scientific Meeting, 2009 Gerontological Society of America Meeting, and the 2010 American
Geriatrics Society Annual Scientific Meeting.
Update: In this report period, the Institute of medicine released new guidelines on vitamin D. These
new guidelines motivated revision of study design and protocols in this reporting period. The new pilot
protocol was approved by the IRB. The CTU is in the process of study field implementation
(anticipated June 2011). The use frailty registry information has critical importance for efficient
recruitment.
Weight Loss in Older Adults
Background: In response to the Funding Opportunity Announcement (FOA) Program Announcement
(PA) – Investigator-Initiated Multi-Site Clinical trials (R01), a grant application for a 5-year, multicenter randomized clinical trial to determine benefits and risks of behavioral weight loss intervention
in older adults is being prepared (PIs: Dr. Svetkey, Duke University; Dr. Clark, Johns Hopkins
University; Dr. Brantley, Pennington Biomedical Research; and Drs. Hollis and Stevens, Kaiser
Permanente's Center for Health Research in Portland, OH). Anticipated submission to the National
Heart, Lung, and Blood Institute is October of 2010. The CTU has been collaborating with the
preparation of this application. Specifically, Dr. Chaves, who will serve as a co-investigator in this
application, has provided his expertise in geriatric functional assessment vis-à-vis study design, in
particular definition of trial’s functional outcomes.
Update: The grant was not funded by the NHLBI. The grant was resubmitted to the NIA, and decision
is pending as of this time.
Other Research Projects
In this report period, the CTU continued to provide major support to Dr. Wang’s project (RCD Core)
on Physiologic and Molecular Basis of the Syndrome of Frailty (IRB# AAC98-10-14-01). In addition,
the CTU started supporting the following new projects: (a) Lifestyle Intervention in Older Adults with
Sleep Apnea (IRB#NA 00040314), PI Dr. Devon Dobrosielski; (b) Investigations of the Vestibular
Reflexes (IRB # NA_00035749), PIs Drs. John Carey/Yuri Agrawal; (c) Effects of Anesthesia on
Cognitive Decline in Older Adults Undergoing Surgery (IRB# NA_00017963), PI: Dr. Jeremy
Walston; and(d)Treatment burden in older adults with multimorbidity (IRB# NA_0023727), PI: Dr.
Cynthia Boyd.
Year 8 (2010-2011) RCDC-supported Junior Faculty:
RCDC-1: Cindy Roy, PhD: Dr. Roy is Assistant Professor of Geriatric Medicine and Gerontology.
Dr. Roy’s supported officially ended in December 2010.
Dr. Roy completed her doctoral thesis, focused on cellular iron biology, in the laboratory of Caroline
Enns, PhD at Oregon Health Sciences University. Under the mentorship of Nancy Andrews, MD, PhD
at Harvard Medical School, Dr. Roy extended her expertise to develop and characterize the Hepcidin
transgenic mouse as a model of anemia of chronic inflammation. While presenting this mouse model at
a workshop hosted by the National Institute on Aging, Dr. Roy met Jeremy Walston, MD and was
introduced to the geriatric syndrome of frailty and the strong geriatrics research program at Johns
Hopkins University. In light of the workshop, Dr. Roy was struck by the great need for mouse models
in geriatric research, and the limits in our knowledge of anemia in older adults. Excited by the potential
for meaningful translational impact and the opportunity to serve older adults with her research
expertise, Dr. Roy gratefully accepted a faculty position within the Division of Geriatric Medicine at
Hopkins.
Dr. Roy’s RCDC-supported project studies the use of inbred mice to model anemia and inflammation
and to independently test the impact of these linked biological processes on physical function with age.
Her main objective, to identify the molecular mediators which connect aging, inflammation,
erythropoiesis, and physical function in mice, is explored with the following specific aims:
1. To determine whether interleukin-6 (IL-6) is required for the anemia induced by sterile abscess
or aging in mice.
2. To determine whether the expression of genes required for hemoglobin synthesis and erythroid
proliferation is inhibited in erythroblasts of aged mice, mice with sterile abscess, and Hepc Tg+
mice.
3. To determine whether grip strength and functional activity are similarly impaired with elevated
Hepc or elevated IL-6 in age- and hemoglobin-matched anemic mice.
Dr. Roy’s support from the OAIC helped her to build her research program devoted to unraveling the
molecular causes and functional consequences of anemia in older adults. Partnership with the OAIC
provided resources in the following areas:
1. Access to experts to train her in appropriate principles of study design and analysis.
2. Access to experts to share their molecular and genetic expression expertise.
3. Access to experts in the biology of aging, chronic disease, and multisystem decline.
4. Access to expertise and infrastructure supporting translational research.
Results/Updates:
We have observed that aged C57BL/6 mice have an anemia consistent with anemia of inflammation.
We have purchased 10 retired female breeder IL-6 deficient and 10 retired female breeder C57BL6/J
control mice. We have completed data collection through 24 months of age. Multiplex proinflammatory cytokine analysis on the serum of these mice indicates C57BL/6 mice have increased IL6 and KC expression at 24 months (p<0.05), consistent with activation of NFB. No significant
changes in IFN, IL-1 or TNF were observed. 24 monthIL-6-deficient mice had a very interesting
proinflammatory cytokine expression pattern. Serum KC and TNF concentrations were significantly
lower than C57BL/6 while IL-10, IFN and IL-12p70 were significantly higher. Whether this new
inflammatory pattern contributes to the decrease in hemoglobin in IL-6-deficient mice from their
baseline, or whether this pattern spares the hemoglobin in aged IL-6-deficient mice is currently
unclear, but we plan to test the individual effects of IL-6 and IFN on erythroid maturation in vitro to
investigate further. Overall, these data suggest inhibiting IL-6 activity could spare hemoglobin
concentration in older adults.
Dr. Roy is actively working toward testing this hypothesis in anemic older adults through her
participation in the Partnership for Anemia Clinical and Translational Trials in the Elderly (PACTTE),
an NIA-sponsored, UO1 consortium. As a member of the consortium, Dr. Roy has participated in the
development of a clinical trial acetylated salicylate that is known to inhibit NFB.
Of the functional parameters measured in these mice (grip strength, rotorod performance, and activity),
we found that the relationship between activity (assessed as the number of times the mouse crosses the
mid-line of a new, clean cage in a 5 minute trial) and hemoglobin varied between C57BL/6 and IL-6deficient mice. While activity positively correlated with hemoglobin in C57BL/6 mice (= 1.03 ±
0.957, p=0.02), activity negatively correlated with hemoglobin in IL-6-deficient mice (=-1.14 ±
0.607, p=0.06). This may be due to a smaller dynamic range for hemoglobin concentrations in the IL6-deficient mice, a trend toward increased activity with age, or both.
We have started aging 15 Hepcidin transgenic mice, but have lost half of them before 18 months of
age. Some deaths were related to euthanasia for ulcerative dermatitis or rectal prolapse. Other deaths
were for unknown causes, which may be related to their anemia. We have decided to shorten the aging
time course to 15 months and will collect our first biochemical data set on these mice in April 2011.
Additional short-term goal include: analysis of gene expression in liver and muscle of 24 month
control and IL-6-deficient mice; resubmission of manuscript concerning anemia in mice with sterile
abscess by 5/2011; submission of manuscript concerning anemia in aged/frail/IL-6 mice by 6/2011.
Paper Development: Currently revising manuscript regarding anemia in sterile abscess model.
Developing a brief report contrasting hematologic parameters in C57BL/6 versus il6-deficient aged
mice and a brief report characterizing the mixed iron deficient anemia and anemia of inflammation in
frail (il-10-deficient) mice.
Papers Accepted:
Tanaka T, Roy CN, Yao W, Matteini A, Semba RD, Arking D, Walston JD, Fried LP, Singleton A,
Guralnik J, Abecasis GR, Bandinelli S, Longo DL, and Ferrucci L. A Genome-Wide Association
Analysis of Serum Iron Concentrations. Blood 2010; 115(1):94-96. PMID: 19880490
Semba RD, Patel KV, Ferrucci L, Sun K, Roy CN, Guralnik JM, Fried LP. Serum antioxidants and
inflammation predict red cell distribution width in older women: The Women's Health and Aging
Study I. Clin Nutr. 2010 Oct;29(5):600-4. 2010 Mar 22. [Epub ahead of print] PMID: 20334961
Presentations: After presenting an invited talk in the Educational Program of the American Society for
Hematology annual meeting in December of 2010, and publishing "Anemia in Frailty" in Clinics in
Geriatric Medicine in February 2011, I was invited by the British Society for Haematology to give the
Dacie Plenary Lecture at their Annual Scientific Meeting concerning the anemia of aging in April 2011
and to write a review on the same topic.
MSTAR student, Tiffany Cao, will present the results of the IL-6 mice with a poster entitled,
“Interleukin-6 deficiency protects aged mice from declines in hemoglobin and physical performance”
at the American Geriatrics Society Annual Meeting in Washington, DC in May 2011.
Grant Development: The RO1 application submitted to NIDDK in October 2010 to develop preclinical trials for the use of non-acetylated salicylates for the treatment of anemia in aged and chronic
disease populations was unscored. After review of summary statements with Dr. Walston, and
publication of the two papers above, she plans to revise and resubmit.
RCDC-2: George Wang, MD, PhD: Dr. Wang obtained his undergraduate degree at Johns Hopkins
University in Biomedical Engineering, his medical degree at the State University of New York,
Downstate College of Medicine, completed an internal medicine residency and clinical geriatrics
fellowship at the University of Medicine and Dentistry of New Jersey, and 3 years of research
fellowship in geriatric medicine at Johns Hopkins. He is also pursuing a PhD from the Graduate
Training Program in Clinical Investigation (GTPCI), sponsored jointly by the Johns Hopkins
University School of Medicine and the Bloomberg School of Public Health. The GTPCI is a nationally
recognized program specifically designed to rigorously train physicians for careers in patient-oriented
research. Dr. Wang’s long-term goal is to become an independent investigator focused on identifying
etiologies that trigger age- or disease-related alterations in the immune system that underlie some of
the vulnerability observed in frail, older adults. Dr. Wang has been a regular participant in the Biology
of Frailty working group on the Hopkins Bayview Campus, and has an ongoing mentorial relationship
with OAIC co-PI Dr. Walston.
The overarching hypothesis of Dr. Wang’s RCDC-supported work is that identifiable causative factors
initiate and perpetuate the inflammation observed in frailty and that frailty-associated dysregulations in
the immune system contributes to this inflammation. He has begun to test this hypothesis by
examining chronic cytomegalovirus (CMV) infection as a model of frailty pathogenesis. Specifically,
he hypothesizes that in a subset of humans who eventually become frail, persistent CMV infection
leads to a chronic inflammatory state and, perhaps through frequent reactivation, causes an
accumulation of CMV-specific T-cell clones, leading to a contracted T-cell receptor repertoire
diversity, and an overproduction of inflammatory cytokines. The resultant limited capacity of the Tcell compartment to respond to antigenic challenges could explain, in part, the increased vulnerability
of frail older adults to stressors such as infections and cancers. With this background in mind, he
studies the following specific aims:
Specific Aim 1: To determine the dose-response relationships among CMV antibody titer, interleukin-6
(IL-6), and frailty in a nested cross-sectional study within the Women’s Health in Aging Study
(WHAS).
Specific Aim 2: To determine the interrelationships between immune regulation and frailty by
a. Measuring autoimmune antibody titers in the same nested cross-sectional WHAS cohort
b. Measuring CMV-specific T cell numbers, phenotype, and function in a case-control
cohort of frail and non-frail older adults.
Specific Aim 3: To determine whether the immunologic alterations identified above increase the future
risk of developing frailty, using a nested longitudinal study design within WHAS.
Results/Updates:
Autoimmunity and frailty
Since a close clinico-pathologic association exists between inflammation and autoimmunity, we
hypothesized that autoimmunity, triggering or triggered by inflammation, might contribute to the
development of frailty in some older adults. With the support of the OAIC RCDC, we measured
thyroid autoantibodies and antinuclear antibodies (ANA), representing organ-specific and systemic
autoantibodies, respectively, in the sera of older women from a combined WHAS I & II cohort. We
found, surprisingly, that community-dwelling older women who were seropositive for thyroglobulin
and thyroid peroxidase autoantibodies were less likely to be prefrail and frail than were seronegative
women, independent of thyroid function status. Whether this finding originates from differences in
immune system function and homeostasis among women classified as nonfrail, prefrail, and frail, or it
reflects changes in the thyroid target organ remains to be elucidated. A manuscript reporting these
results is in press for the Journal of Clinical Endocrinology and Metabolism (16). A one-page
commentary on this study will be featured in the February issue of Endocrine News. Although we have
already planned follow-up studies to further investigate the implications of these findings, these plans
are not included in this RCDC application.
CMV infection and the risk of incident frailty and mortality
With the support of the OAIC RCDC, we tested the hypothesis that higher CMV antibody
concentrations are associated with a higher risk of incident frailty and mortality. We conducted a
prospective cohort study nested within WHAS I and II, measuring baseline serum CMV IgG antibody
concentration to determine the effect of CMV infection on incident frailty and mortality in
immunocompetent older women. We found that older women in the highest quartile of CMV IgG
antibody concentration had higher risks of three-year incident frailty (hazard ratio, 3.46; 95% CI,
1.45−8.27) and five-year mortality than those who were CMV seronegative (hazard ratio, 3.81; 95%
CI, 1.64−8.83). After adjustment for potential confounders, the highest quartile of CMV antibody
concentration independently predicted a higher risk of five-year mortality (hazard ratio, 2.79; 95% CI,
1.22−6.40). Although there was a suggestion of an independent association between the highest
quartile of CMV antibody concentration and three-year incident frailty, the 95% CI of the hazard ratio
contained the null value (hazard ratio, 2.26; 95% CI, 0.89−5.75). A manuscript reporting these results
has been submitted to the American Journal of Epidemiology.
CMV-specific memory CD8+ T cells in frail and nonfrail adults
Dr. Wang conducted tetramer-based polychromatic flow cytometry to characterize CMV-specific
memory CD8+ T cells from community-dwelling frail and nonfrail older adults. Dots plots derived
from flow cytometry data demonstrate detectable populations of CMV-specific (pp65 tetramer+)
CD8+ T cells from the PBMC specimens of four older individuals, with higher frequencies of CMV
tetramer+ CD8+ cells noted in the frail individuals in this small sample of four. In a separate
experiment, PBMC from one of the two pairs of participants (Pair #1) were cultured in medium alone,
with CMV pp65 or IE1 pooled peptides, or with Staphylococcal enterotoxin B (SEB), a mitogen.
Despite the remarkably higher frequency of CMV tetramer+ CD8+ T cells in the frail individual in
Pair#2, a lower proportion of the CMV-specific CD8+ T cells in the frail individual responded to CMV
peptide stimulation by secreting interferon-γ. The significance of this finding in only one pair of
participants is unclear and is being investigated further in additional participants from the ongoing
cohort recruited by Dr. Wang. Such experiments cannot be done in WHAS because of the significantly
greater number of PBMC needed. For the project proposed here, we focus on enumerating the
frequencies of CMV-specific memory CD8+ T cells, without performing any in vitro stimulation, and
determining the CMV-specific TCR repertoire longitudinally.
Measurement of antigen-specific T-cell receptor repertoire diversity
The OAIC RCDC support made it possible for Dr. Wang to travel to the immunology laboratory of Dr.
Peter Doherty at St. Jude Children’s Research Hospital in Memphis, Tennessee, to develop a singlecell clonotypic method of investigating antigen-specific TCR diversity in humans. This method is
grounded in the isolation of single epitope-specific CD8+ T cells, reverse-transcription polymerase
chain reaction (PCR) of total mRNA, PCR-based amplification of the complementarity-determining
region 3 (CDR3) of the TCR, and CDR3 sequencing. Precise T-cell clonal identity and frequency are
obtained. Unlike information derived from other methods of TCR diversity analysis, this information is
amenable to rigorous downstream statistical analysis and can provide precise signature patterns of
TCR diversity over time. A “methods paper” describing the development of this TCR diversity
analytical tool has been completed by Dr. Wang and will be submitted shortly.
Manuscripts:
Wang GC, Talor MV, Rose NR, Cappola AR, Chiou RB, Weiss C, Walston JD, Fried LP, Caturegli P.
Thyroid autoantibodies are associated with a reduced prevalence of frailty in community-dwelling
older women. J Clin Endocrinol Metab. 2010 Mar;95(3):1161-8. PMID: 20061418
Wang GC, Kao L, Murakami P, Xue QL, McDyer J, Chiou R, Semba RD, Casolaro V, Walston JD,
Fried LP. Cytomegalovirus infection and the risk of mortality and frailty in older women: a prospective
observational cohort study. 2010 Am J Epi. In press.
The following manuscripts are under preparation (tentative titles): 1. Thyroid function and the risk of
frailty in community-dwelling older women 2. Herpesvirus infections and the risk of frailty and
mortality in community dwelling older women 3. Methodologic issues in cytomegalovirus-related
epidemiologic studies 8. The following manuscript is being revised for Science Translational Medicine
(see above): Comprehensive characterization of human epitope-specific T-cell receptor αβ repertoires.
Abstract:
Wang GC, Xue QL, Xia J, Cappola AR, Walston JD, Rose NR, Fried LP, Caturegli P. Thyroid
Function and Frailty in Community-Dwelling Older Women: The Women’s Health and Aging
Studies. Oral Paper Session Presentation at the 2010 Annual Scientific Meeting of the American
Geriatrics Society, Orlando, Florida. May, 2010.
Wang GC . Herpesvirus Infections and the Risk of Frailty and Mortality in Community-Dwelling
Older Women: The Women’s Health and Aging Studies. Selected for oral presentation at the 2011
Annual Scientific Meeting of the American Geriatrics Society.
Grants:
Dr. Wang was awarded the NIH K23 Award in October 2010, ending his OAIC RCDC salary support.
He will continue to receive external project support and participate in the ongoing RCDC training
activities through 2011.
RCDC-3: Frank Lin, MD, PhD, “Hearing Loss and Frailty”:
Dr. Frank Lin is currently a junior faculty member in the Department of Otolaryngology-Head & Neck
Surgery at the Johns Hopkins School of Medicine where his clinical practice is dedicated to hearing
loss and otology. He previously completed a PhD in Clinical Investigation at the Johns Hopkins
Bloomberg School of Public Health where he applied conceptual models of functioning developed by
the World Health Organization to the assessment of pediatric cochlear implantation (CI). With OAIC
support of protected time for his career development in frailty research, Dr. Lin seeks to better
understand the effects of hearing loss on the development and consequences of frailty in older adults.
Building on his prior research experience in utilizing conceptual models of health outcomes, Dr. Lin
has developed a novel framework to understand and study the impact of hearing loss in older adults
that draws on the fields of cognitive psychology, social epidemiology, gerontology, and the hearing
sciences. In Aim 1a, he will use two established prospective datasets (Women’s Health and Aging
Study, Baltimore Longitudinal Study of Aging) to study the association of hearing loss with frailty and
mediating domains of cognition and social isolation. In Aim 1b, he will then explore whether there
may be a common biologic origin for hearing loss and frailty by measuring hearing thresholds in frail
(IL-10tm/tm) versus control mice in an interdisciplinary collaboration between aging and auditory
science laboratories. In Aim 2, Dr. Lin studies whether hearing loss in frail individuals is associated
with a greater risk of developing incident adverse events such as functional decline or hospitalization.
This work will provide further insights into the biology of frailty and may identify potential pathways
for intervention with aural rehabilitative strategies and devices.
Results/Updates:
1) BLSA dataset: he has been analyzing the BLSA dataset over the last several months examining the
relationship of hearing loss with cognitive function which may mediate the association of hearing loss
with frailty. His completed analyses indicate that hearing loss is associated with poorer cognitive
function on measures of global cognition, memory, and executive function. This manuscript is
currently under review.
2) WHAS dataset: Dr. Lin applied for access to the WHAS dataset in August and was notified that his
proposal to study the association of hearing loss with frailty and other adverse outcomes was approved
at the beginning of this year. He is currently in the process of working with the WHAS investigators to
build the specific dataset needed for these analyses.
3) NHANES dataset: Because of the initial delay in obtaining access to the WHAS dataset, Dr. Lin
pursued additional studies using publicly-available NHANES data to examine the epidemiology of
hearing loss and the association of hearing loss with social isolation and functioning. He has had one
manuscript examining hearing loss epidemiology in older adults >70 recently published. Two other
manuscripts are currently under review (one manuscript demonstrating an association between skin
color (as measured by Fitzpatrick skin type) and hearing loss, and the other manuscript demonstrating
an association of hearing loss with cognition using the Digit Symbol Substitution Test).
Short-term goals include: In BLSA, he is currently analyzing the association of hearing with
longitudinal changes in MRI structural morphometry and cognitive scores. Dr. Lin is planning separate
studies to examine the association of hearing loss with functional decline. In NHANES: He is currently
conducting multiple additional studies investigating the association of hearing loss with social
isolation, functioning, and health care utilization. In terms of didactics: Dr. Lin recently finished a
course on genetic epidemiology in anticipation of initiating genetic epidemiology studies of hearing
loss in the BLSA and HealthABC studies within the next 1-2 years. He is currently sitting in on an
Epidemiology of Aging course.
Manuscripts:
Accepted papers:
1) Hearing loss prevalence and risk factors among older adults in the U.S. JGMS Feb 2011.
Under Review:
1) Hearing loss and cognition in the Baltimore Longitudinal Study of Aging. Neuropsychology.
2) Association of skin color, race/ethnicity, and hearing loss among adults in the United States.
AJPH.
3) Hearing loss and cognition among adults in the United States. JGMS
Presentations:
1) Hearing loss and incident dementia in the Baltimore Longitudinal Study of Aging, Podium
presentation, 2010 Gerontological Society of America Annual Meeting, New Orleans, 11/1911/23/2010.
2) Hearing loss and incident dementia, Poster presentation, Mid-Winter Meeting of the
Association for Research in Otolaryngology, Baltimore, February 2011
3) Hearing loss and cognition in the Baltimore Longitudinal Study of Aging, Podium presentation,
American Auditory Society Meeting, March 2011
4) Prevalence and epidemiology of hearing loss among older adults in the United States. Poster
presentation, American Auditory Society Meeting, March 2011
5) Prevalence and epidemiology of hearing loss among older adults in the United States. Poster
presentation, Pepper OAIC Annual Meeting, April 2011
Grants: K23 application entitled "Hearing loss and Aging" was awarded with funding beginning
12/1/2010. His RCDC funded salary support ended with that award, but he will continue to participate
in RCDC training activities for 2 additional years, and will receive external project support as needed.
In addition, Dr. Lin submitted a grant application with Dr. Walston in response to an NIDCD RFA to
establish a research mentoring network. The application proposed to build a multidisciplinary research
mentoring network dedicated to age-related hearing loss that will leverage the current infrastructure of
the 12 Pepper OAIC's.
RCDC-4: Peter Abadir, MD, “Age Related Change in Angiotensin Receptors and its
Contribution to the Chronic Inflammation.”
Aging is associated with enhanced inflammation. An altered ratio between angiotensin receptors AT1R
and AT2R results in induction of inflammation in animal models. The effects of aging on the
expression of AT1R and AT2R in humans and the contribution of changes in AT1R and AT2R to
increased inflammation in the older have not been previously studied. Our preliminary evidence
suggests that frail older adults have up-regulation of AT1R, down-regulation of AT2R expression and
implicate IL6 in this imbalance.
We hypothesize that aging is associated with changes in AT1R and AT2R expression in immune
system cells and that these changes are driven by age related alterations in DNA methylation of AT1R
and AT2R genes. Further we hypothesize that these changes contribute to the increased production of
inflammatory cytokines in older individuals which in turn will further heighten the divergence in
AT1R and AT2R expression.
To test our hypotheses we:
1. Measure changes in gene expression, protein synthesis and specific gene DNA methylation of
AT1R and AT2R in immune system cells from young (20-30 y), robust (70-90y) and frail (7090y) human subjects (N=20 in each group) using Q-PCR, western blot, confocal microscopy,
and DNA methylation analysis.
2. Evaluate the contributions of AT1R and AT2R to cytokine production in the older individuals
by incubating immune system cells from the same individuals with specific AT1R and/or
AT2R blockers and measuring cytokines with ELISA and Bio-Plex cytokine assays at baseline
and in response to treatment(s).
3. Assess the feedback of inflammation on AT1R and AT2R expression by incubating immune
system cells from the same subjects with IL-6. Q-PCR and western blot will be used to quantify
the change in expression of AT1R and AT2R in response to IL-6 treatment.
Results/Updates:
1. PROGRESS: My studies focusing on changes in the renin angiotensin system with aging. We have
been actively recruiting patients and performing experiments. Below is a brief introduction and
description of our experiments and update on results.
Introduction
Aging is associated with enhanced inflammation. An altered ratio between angiotensin receptors AT1R
and AT2R results in induction of inflammation in animal models. The effects of aging on the
expression of AT1R and AT2R in humans and the contribution of changes in AT1R and AT2R to
increased inflammation in the older have not been previously studied.
We hypothesize that aging and the condition of frailty is associated with up-regulation of AT1R and
down-regulation of AT2R expression and function in immune system cells. We further hypothesize
that these receptor changes contribute to the increased production of inflammatory cytokines in older
individuals that will further heighten the divergence in AT1R and AT2R expression.
Population and Methods:
Young, healthy adults (age 20-30) and two comparison groups that consist of (1) robust, older adults
(age 70-90), and (2) frail, older adults (age 70-90), living in the Baltimore, Maryland area were
recruited for the proposed study. Frailty was determined using a validated frailty screening criteria that
include weight loss, grip strength, energy level, physical activity, and walking speed and previously
published exclusion criterion. From these subjects, monocytes will be utilized for the proposed studies.
Immunolocalization and confocal microscopy was used to detect AT1R and AT2R in human
monocytes. Q-PCR and western blotting was used to measure changes in gene and protein expression
of the angiotensin AT1R and AT2R in monocytes. To further delineate the specific expression of AT1R
and AT2R on the membranes of monocytes, immunofluorescence and flow cytometric analysis of
monocytes was used to determine the percentage monocytes expressing AT1R, AT2R, both AT1R and
AT2R or neither.
As IL-6 is one of the key inflammatory mediators in older adults, the effect of IL-6 on the expression
of AT1R and AT2R in monocytes was assessed by incubating monocytes from young, robust and frail
individuals with 100 ng/ml of IL-6 for 24 hours. In order to determine and compare the contribution of
changes in AT1R and AT2R to increased inflammation in older individuals we incubated human
monocytes from young, robust and frail individuals with specific in-vitro administered AT1R and/or
AT2R blockers Valsartan (VAL) and PD at a serially increasing concentration. Changes in AT1R and
AT2R gene expression and changes in IL-6 and TNFα were measured using Q-PCR and mesoscale
multiplex system.
Results: To date, we have recruited 6 individuals for pilot studies. (N=2 each group, total number=6).
Using immunolocalization and confocal microscopy we detected AT1R and AT2R in lymphocytes and
monocytes from young (N=2) individuals on the cell membrane, and intracellularly mainly in the
perinuclear region.
Our preliminary data suggest that aging is associated with down regulation of the gene and protein
expression of AT1R and AT2R in human monocytes as compared to young control. However our
experiments also suggest that monocytes from frail older adults may have differential regulation of the
angiotensin receptors, leading to up-regulation of AT1R and down-regulation of AT2R expression.
We used immunofluorescence and flow cytometric analysis to determine the percentage of monocytes
expressing the angiotensin receptors on the cell membrane. In young and robust older subjects most of
monocytes were not expressing either AT1R or AT2R. In contrast there was a predominance of AT1R
expression in frail monocytes (31.3%).
Incubation of monocytes from young, robust and frail individuals with 100 ng/ml of IL-6 for 24 hours
led to up-regulation of AT1R and down-regulation of AT2R, mimicking the changes in expression of
AT1R and AT2R in frail older individuals with no treatment as compared to young control, again
suggesting a possible role for IL-6 in the imbalance between receptors. The most significant increase
(32 fold) in AT1R gene expression was observed in monocytes from young individuals. Preliminary
results from the incubation with agonists and antagonists suggest a significant decrease in the
production of IL-6 and TNFα from monocytes in response to the blockade of AT1R, while
paradoxically the blockade of AT2R increased the production of IL-6, and TNFα.
Discussion:
These preliminary data attest to our ability to detect and quantify surface AT1R and AT2R expression
on human leukocytes, and suggest that there may be detectable differences among leukocytes from
frail subjects. These early findings now require validation in larger populations, an effort which is
already underway and which should help us begin to define changes in the angiotensin system with
aging and frailty and its contribution to chronic inflammation.
2. Publications :
Abadir PM, Walston JD, Carey RM, Siragy HM. Angiotensin II Type-2 Receptors Modulate
Inflammation Through Signal Transducer and Activator of Transcription Proteins 3
Phosphorylation and TNFα Production. J Interferon Cytokine Res. 2011 Feb 2.
3. Presentations / Abstracts: Abstract presented at the American Geriatrics society 2010 and 2011
annual meetings, T.F Williams Scholars session.
4. Grants: Dr. Abadir was awarded NIA K – 23 award. The award titled, “Age Related Changes in
Angiotensin Receptors and its Contribution to Chronic Inflammation” will allow him to evaluate
the age-related changes in the renin angiotensin system, and its interface with chronic inflammation
that may play a role in frailty and late life vulnerability. Although this award ended Dr. Abadir’s
formal OAIC RCDC support, he will continue to receive external project support by the RC-1 and
RC-2, and will participate in RCDC training seminars.
RCDC-5 Devon Dobrosielski, PhD, “Effects of a Lifestyle Intervention in Older Adults with
Sleep Apnea.” Frailty is a condition associated with age and characterized by a decrease in
physiological reserve and increased risk for adverse health-related outcomes, especially in the presence
of co-morbid conditions. Sleep apnea is also highly prevalent with increasing age. Both conditions
share common pathologies, suggesting that sleep apnea may increase the risk of developing or
exacerbate the consequences of frailty. Published data and our own preliminary data support lifestyle
interventions as strategies for treating sleep apnea and associated co-morbidities, thereby highlighting
a potential and feasible approach to reduce the incidence or progression of frailty. The emphasis of this
mentored research is consistent with one of the key missions of the Hopkins OAIC - to identify causes
and develop treatments for frailty. The specific aims are to: 1) Determine the effectiveness of a
lifestyle intervention, consisting of a weight loss diet and supervised exercise, on reducing sleep apnea
in older adults, 2) Determine whether this intervention is effective at improving parameters that are
common to both sleep apnea and frailty, such as poor physical functional capacity and body
composition, impaired or abnormal cardiovascular and metabolic function and increased levels of
inflammation. To enhance our ability to carry out these aims, in addition to the OAIC award, we will
also make extensive use of the resources available at the Institute for Clinical and Translational
Research (ICTR) and the Johns Hopkins Sleep Clinic located at Johns Hopkins Bayview. The potential
impact of this work is the application of broadly available lifestyle changes for older persons with
sleep apnea who may be at risk for cardiovascular morbidity and frailty. Results from this pilot study,
if positive, will be used to form the basis of a subsequent larger scale trial. The role of lifestyle
interventions for treating sleep apnea and associated co-morbidities has been identified by the NIH as
an emerging research area. Accordingly, in a larger, fully powered trial, a potential aim would be to
examine the effectiveness of a weight loss diet or exercise training alone or in combination with other
treatments for sleep apnea (i.e., continuous positive airway pressure (CPAP)) in older adults.
Results/Updates: Notice of grant award received 6-30-10; IRB application submitted on 7-20-10;
Response to issues sent by PI on 8-5-10; Revised IRB application sent on 8-30-10; IRB convened 913-10; Study approved 10-18-10 (IRB# 00040314). An advertisement appeared in the Baltimore Sun
paper during the first week of Jan 2011. CRU in-service was completed on 11-30-10. The December
month efforts were devoted toward collecting test/re-test reliability for the brachial artery flowmediated dilation and abdominal ultrasound testing protocols. Advertisements have yielded 25 phone
calls. Nine individuals have been screened (5 are in various stages of baseline testing.. Four men
underwent sleep studies and qualified based on AHI criteria. Three of these individuals are actively
enrolled in the program. 1 dropped out due to "family circumstances". Established partnership with
Steven Prior, Assistant Professor of Medicine at the University of Maryland and OAIC supported
investigator. He is analyzing endothelial progenitor cell number from blood samples in LISA subjects
before and after intervention. No extra burden to participant. Jason Kirkness PhD (Bayview Pulmonary
Medicine) was added to the study team. He will facilitate patient recruitment from the pulmonary
clinic as well as assist in analysis of PSG airflow data. Training: successfully completed Biostatistics I
& II in School of Public Health (Dec 2010).
Short-term goal is to enroll 10 patients into intervention by July 1, 2011. Another advertisement will be
placed into the Baltimore Sun in March. Long term goal is to enroll the entire sample (n=20) by the
end of 2011. With additional ads and recruitment from pulmonary clinic, this should be achievable.
Papers published in quarter: Moseley KF, Dobrosielski DA, Stewart Kj, Jan De Beur SM, Sellmeyer
DE. Lean mass and fat mass predict bone mineral density in middle-aged individuals with non-insulin requiring type 2 diabetes mellitus. Clin Endocrinol (Oxf). 2011 May;74(5):565-71. doi:
10.1111/j.1365-2265.2010.03965.x. Epub 2010 Dec 24.
Papers in review: "The association of arterial shear and flow-mediated dilation in diabetes" submitted
to Vasc Med. "The relation between hepatic fat and LVDD" submitted to Am J Gastro.
Papers in development: "Changes in arterial flow patterns following 6 months of exercise in diabetes."
"Exercise training and the cardiovascular consequences of sleep apnea: plausible mechanisms for
improving sleep and cardiovascular health." "Visceral fat loss following exercise training in diabetes
and hypertension."
Abstracts: Three abstracts were accepted for presentation at annual meeting of the American College
of Sports Medicine.
Grants: K23 patient oriented career development award submitted Feb 12, mentors Stewart and Lima.
R34 "Lifestyle interventions in sleep apnea: Effects on sleep and CV health" was resubmitted on
March 10, 2011.
RCDC-6: Aliaksei Pustavoitau, MD, “A Prospective Cohort Study Evaluating the Use of
p16INK4a Transcriptional Factor Level as a Marker of Molecular Age and Predictor of
Perioperative Outcomes”: Biomarkers have found broad utility in various fields of medicine due to
their ability to reflect physiologic and pathologic phenomena. More recently, several biomarkers of
aging have been identified. We plan to establish the biological role and clinical utility of biomarkers of
aging in the perioperative period. Once their utility is identified, we envision biomarkers will be
incorporated into models of perioperative outcomes in various patient populations. Specifically, we
propose to investigate a predictive role of transcriptional factor p16INK4a (p16) as a biomarker of
aging in patients undergoing elective coronary artery bypass surgery.
Coronary artery bypass is a commonly performed procedure in elderly patients accounting for over
200,000 surgical procedures annually. Models predicting perioperative outcomes after coronary artery
bypass surgery commonly include chronological age. However, chronological age does not accurately
describe biology or physiology of aging. Potential other measures reflecting aging process include
frailty status and biomarkers. Transcriptional factor p16 is an important cell cycle regulator, and
increases are associated with aging in various tissues and organisms, including humans. Recently, a
new assay was developed to measure p16 levels in CD3+ lymphocytes derived from the peripheral
blood, thus making it a practical test.
Specific aims: 1) To investigate associations between p16 levels in CD3+ LDPB of elderly patients
undergoing coronary artery bypass surgery and frailty and chronological age. 2) To investigate
association between p16 levels and length of ICU and hospital stay, morbidity and mortality.
Research design and methods: Seventy-six patients older than 65 years undergoing elective coronary
artery bypass surgery will be prospectively recruited and followed for 30 days post-operatively for
clinical outcomes. Patients with concurrent acute illnesses, poor myocardial performance, combined
surgical procedures, and undergoing emergency surgical procedures will be excluded. Preoperatively,
their demographic data, co-morbidities and disability status will be established, frailty status will be
measured and blood collected for p16 measurement. P16 levels will be correlated with chronological
age and frailty status. P16 levels will further be correlated with length of hospital and ICU stay,
morbidity and mortality related to coronary artery bypass surgery. Variables known to affect p16
levels: smoking, physical activity, and IL-6 levels will be incorporated into the final model.
Grants: Dr. Pustavoitau is just beginning his award, and will be fully supported by RC-1, RC-2, and
by CTU in order to develop necessary data sets, biological measurements, and recruit subjects into his
protocol. He meets monthly with Dr. Walston and has begun planning for a submission of a K-23
award within one-two years.
II.D.
PILOT / EXPLORATORY STUDIES CORE
Peter Rabins, M.D., M.P.H., Core Leader
410-955-6736
410-614-1094 FAX
[email protected]
The overall goals of the Pilot Exploratory Studies Core are to foster this OAIC’s objectives by
cultivating and supporting cutting edge pilot and exploratory studies that will advance the development
of effective prevention and/or therapies for frailty. This Core sets scientific goals for the next stages of
frailty research in collaboration with the Leadership Council (see Leadership and Administrative
Core), and then works to identify investigators whose expertise and career goals would be applicable to
furthering our knowledge in these target areas, and fosters their development of high impact pilot
studies, their conduct, and eventual translation. Overall, this Pilot and Exploratory Studies (P/ES)
Core accomplishes this by funding and mentoring-to-completion and translation pilot studies of novel,
hypothesis-driven research that a) establishes potential mechanisms, etiologies, screening approaches
or evaluates potential therapies to prevent or ameliorate the syndrome of frailty, and b) establishes
preliminary data in these areas that will lead to substantive, long term external funding that can bring
this research to completion.
Building on these overarching goals, the specific aims of this core are to:
1. Advance the science and translation of the field of frailty research by providing intellectual
leadership to: a) identify areas of research with the potential for developing interventions that prevent
or treat frailty, b) identify new and established investigators with the potential to make significant
contributions to the study of frailty, and encourage and guide them to develop pilot proposals.
2. Support development of optimal pilot proposals, including ensuring optimal utilization of the
intellectual and other resources offered by other OAIC cores, as needed. This includes a small pilot
program mechanism to foster this OAIC’s objectives by cultivating and supporting cutting edge pilot
and exploratory studies that will advance the development of effective prevention and/or therapies for
frailty. The main goal of the Small Pilot Projects program is to fund potentially high impact frailty
research by investigators with ongoing research progress.
3. Provide and conduct longitudinal mentorship from conception to translation for investigators whose
pilot proposals are supported by the OAIC. This will begin with mentorship for the development of
well-designed, hypothesis testing and hypothesis-generating proposals that fit within a pilot project
framework, helping the awardee understand how the project fits into the corpus of research into frailty,
facilitating successful, timely completion of projects, helping resolve problems as they arise during the
course of the research, supporting participation in OAIC seminars and RIPs, and guiding the awardee
in developing follow-up aims and hypotheses as the basis for seeking independent funding and
translation of research. Specifically, this core will help awardees establish a time line for each project,
set expectations for high productivity, monitor progress towards the established goals, make optimal
adaptations to this timeline when research challenges arise, and require that the awardee prepare brief
reports every four months during P/ESC support describing progress made, obstacles encountered and
strategies proposed to overcome these challenges.
4. Increase the visibility of frailty as an important topic by bringing it to the attention of individuals
with the potential to contribute to the study of frailty, by helping awardees present their research at
local and national forums, by placing awardees in contact with other individuals at Johns Hopkins and
nationally whose interests intersect with the topic they are researching, by encouraging discussion of
frailty and the potential application of the pilot studies being supported in clinical, epidemiological and
basic science forums throughout the medical institutions, on clinical services, at specialty society
meetings, and in public health settings, and through high productivity of awardees.
5. Guide the translation of pilot work into a deeper understanding of the basic biology of frailty (top
down) and into interventions that will prevent or treat frailty (bottom up) by discussing the potential
translation of pilot projects to future studies during the development, course, and completion of the
project, and in OAIC seminars. Foster communication and collaboration between awardees and
participants in other OAIC cores to further encourage translation.
Year 8 Pilot/Exploratory Studies (PES):
PES-1: Yuri Agrawal, MD, “Physiology of vestibular dysfunction and clinical implications”: The
geriatric syndrome of frailty, characterized by muscle weakness, weight loss, slow gait, fatigue and
reduced physical activity, significantly increases the risk of devastating outcomes such as falls. The
long term goals of this research are to better understand the contribution of vestibular dysfunction to
the frailty phenotype and to the risk of falls, and as a corollary to explore whether screening for and
treating vestibular dysfunction may mitigate frailty and reduce the incidence of falls. Recent analyses
have shown that vestibular dysfunction is common in the US population, and that the prevalence of
vestibular dysfunction increases steeply with age. However, it is unknown whether the aging process
has global effects on the vestibular end-organ or whether specific structures, e.g. the semicircular
canals or the otoliths, are selectively impaired. Moreover, the clinical implications of specific deficits
of the vestibular end-organ are unclear. The study proposed here aims to characterize the physiologic
nature of the vestibular dysfunction that occurs with aging, and to evaluate whether specific deficits of
the vestibular system are associated with distinct clinical manifestations and consequences. Findings
from this study will be used to guide the development and testing of rational screening, vestibular
rehabilitation, frailty and fall risk reduction strategies in older individuals. Primary aim: To evaluate
whether the normative aging process is predominantly associated with semicircular canal or otolith
dysfunction. Hypothesis: The normative aging process causes greater dysfunction of the otoliths (as
measured by cervical and ocular vestibular-evoked myogenic potential (VEMP) testing) than of the
semicircular canals (as measured by angular vestibulo-ocular reflex (AVOR) and caloric testing) in
individuals age 70 and over, based on results from prior studies. Exploratory aim: To determine if there
are any characteristic clinical features associated with the subtypes of vestibular dysfunction.
Hypothesis: Certain clinical features (e.g. sensation of tilting or lateropulsion, sensation of falling,
sensation of “walking on pillows”) are more significantly associated with otolith dysfunction than
semicircular canal dysfunction in individuals age 70 and over. Exploratory aim: To assess whether
dysfunction of the semicircular canals or of the otoliths is associated with a higher risk of frailty and
falls. Hypothesis: Otolith dysfunction has a greater association with the frailty phenotype and more
significantly increases one-year fall risk than semicircular canal function in individuals age 70 and
over.
Updates / Results: Progress has been made on multiple fronts: 1) Personnel training: investigator has
recruited a vestibular technician, Geraldine Zuniga, who is spending 50% effort on this project. She
has been trained on performing the vestibular physiologic testing (dynamic visual acuity and VEMP
testing) as well administering the clinical otologic and vestibular testing. Investigator has also
established collaborations with OAIC research staff, Jennifer Hughes and Leeondra Thornton, who are
helping to identify possible subjects based on the frailty patient registry maintained at their Center. 2)
Database development: with the help of Dr. Long He from the OAIC Biostatistics Core, the
investigator has developed a secure Access database to maintain all our data. 3) Establish
collaborations: the investigator has established collaboration with Dr. Roni Dinkes at Bayview and
Colleen Ryan-Bane at JHH to perform audiologic testing on all patients at a research cost. 4) Setup and
equipment: the investigator has purchased a research laptop to input data for vestibular physiologic
testing. A research laboratory has been set up out of an office adjoining the OAIC offices at Bayview
where all clinical examinations and testing are performed. The testing apparatus has been calibrated
and ongoing review of the data to ensure quality and validity is performed. A system is in place for
payment of subjects in a timely manner with the help of the Otolaryngology Department business
office which is managing the grant. So far, 30 out of 100 patients have been enrolled. Each patient has
filled out a baseline questionnaire about specific clinical symptoms and has been administered a
clinical examination as well as audiometric and comprehensive vestibular testing. Examination of each
patient takes approximately 2.5 to 3 hours. Data from each patient are being entered into the Access
database. 5) It has become evident through our data collection that participants have a difficult time
deciding what constitutes a “near-fall,” a “fall” or what is not a fall event at all. We are therefore
working on developing a better-defined falls grading scale, whereby specific parameters are used to
classify a fall based on functional impact. Currently we are in the face validation stage, and are
performing semi-structured interviews with providers with various areas of expertise to get their input
into our proposed scale. We are collaborating with Dr. Frank Lin, a member of the Center on Aging
and Health core faculty, in validating this instrument.
Publications/Abstracts/Grants:
• Abstract submitted to 2011 Gerontological Society of America Meeting: Davalos-Bichara M,
Zuniga MG, Carey JP, Schubert MC, Walston JD, Hughes J, Agrawal Y. Vestibular
dysfunction and gait speed in older individuals.
Background:
Gait speed reflects function in several organ systems and has been shown to strongly prognosticate
survival in older individuals. The inner ear vestibular system is known to play an integral role in
balance control and locomotion. Our objectives were: 1) to evaluate vestibular function in older
individuals, and 2) to determine the contribution of vestibular function to gait speed in this population.
Methods:
Community-dwelling participants age ≥70 years underwent two clinical tests of vestibular function: 1)
right and left head impulse testing (HIT; a positive test indicates right or left horizontal semicircular
canal dysfunction), 2) the modified Romberg test (mRT; a positive test suggests difficulty integrating
vestibular information), as well as gait speed measurement on a 4-meter walkway.
Results:
We enrolled 20 participants; 55% were female and the mean age was 76.7 years (SD 4.4). Thirty-five
and thirty percent of subjects had abnormal right and left HITs respectively; individuals with a positive
right HIT were also more likely to have a positive left-sided HIT (p=0.0072). Mean (SD) gait speeds
were lower in subjects with positive vs. negative HITs (right 0.9(0.2) vs. 1.4(0.4) m/s; p=0.0053; left:
1.1(0.7) vs. 1.3(0.3) m/s; p=0.3060.) In addition, gait speeds in subjects with a positive mRT (60% of
participants) were lower than those with a negative mRT (1.0(0.3) vs. 1.6(0.4) m/s; p=0.0037).
Conclusions:
A significant proportion of older individuals have evidence of vestibular dysfunction, which is
associated with a reduction in gait speed. Further quantitative vestibular testing and assessment of fall
risk are in progress.
•
Abstract in preparation for the 2011 Pan American Congress of Gerontology and Geriatrics:
“Validation of the Hopkins Falls Grading Scale.”
PES-2: Rita Kalyani, MD, “Insulin Resistance, Energy Homeostasis, and Frailty”: Background:
Insulin resistance is becoming recognized as a metabolic derangement associated with sarcopenia and
frailty, although the mechanisms are not fully understood. Insulin plays a key role in energy
homestasis and the decoupling of energy balance may contribute to weight loss, frailty and/or
sarcopenia in older adults. The metabolic derangements underlying sarcopenia and/or frailty may be
best identified under challenge testing that give greater insight into an individual’s physiological
reserve. Specific Aims: 1) To determine differences in fasting glucose and insulin levels, related
differences in hormones and inflammatory markers associated with energy metabolism (GLP-1,
adiponectin, leptin, resistin, ghrelin, growth hormone, IGF-1, IL-6), and whether frail compared to
nonfrail or prefrail older women demonstrate hormonal or inflammatory responses to dynamic glucose
testing that are deficient, exaggerated, delayed, prolonged and/or show threshold patterns of response.
2) To determine whether differences in the above hormonal and inflammatory regulators of energy
metabolism are also observed under fasting and challenge conditions among older women with
sarcopenia compared to women without sarcopenia. Methods: We have collected new human
specimens as part of a substudy performed in 79 older women (ages 84 – 95 years, mean 86.7 years)
followed in the Women’s Health and Aging Study II (WHAS II) from May 2008 to March 2009.
During the home substudy visit, women were administered a 75 gram oral glucose tolerance test
(OGTT) after an overnight fast. Blood was drawn at 0, 30, 60, 90, 120, and 180 minutes, centrifuged,
and immediately chilled. Grip strength testing, gait speed over 4 meters, body weight and height were
measured. A questionnaire on exhaustion and physical activity was also administered for frailty
assessment. Grip strength in the lowest quintile of older adults was used to define sarcopenia.
Preliminary Data: After excluding 6 women with prevalent diabetes, average glucose dynamics during
OGTT were examined by frailty status for 73 women (9 frail, 47 prefrail, 17 nonfrail) in Specific Aim
1. There was a stepwise increase in glucose dynamics comparing frail (who had slightly higher fasting
but much higher 2-hour glucose levels) to either prefrail/nonfrail older women suggesting that
challenge testing evoked more dramatic differences than fasting conditions alone. A similar
comparison of average glucose dynamics by sarcopenia status (n=31 with sarcopenia, n=42 without
sarcopenia) will be performed for Aim 2. The differential responses of insulin and related
hormones/inflammatory markers of energy metabolism have yet to be investigated for both aims.
Implications: This study will provide greater insights into the etiology and mechanisms of frailty; in
particular, how metabolic systems are dysregulated in frailty using a novel approach (dynamic glucose
testing). Pilot data from this study will form the basis for a series of future studies examining the
longitudinal associations of insulin resistance, energy homeostasis and frailty. Such research can
ultimately lead to the development and testing of future hormonal or anti-inflammatory interventions
for the prevention and treatment of frailty.
Updates / Results: As the assays for the various hormones of energy metabolism are being run, I have
started to perform descriptive analyses of the data including box-plots and frequency distributions.
These graphical displays were used to identify and validate outliers, log transform skewed
distributions, and identify co-linearity. Bivariate analyses were performed for each hormone with
frailty status using t-tests for normally distributed variables. The results of bivariate analyses in 73
women without diabetes, who were followed as part of the home-study OGTT visit in WHAS II,
demonstrate that median fasting and 2-hour ghrelin levels are significantly lower in frail versus nonfrail women (p=0.04). 2-hour ghrelin values are significantly different by frailty status, and are lower
in frail versus non-frail women (p=0.04). Mean fasting fatty acids (FFA) are higher in frail versus nonfrail women, with a trend towards significance (p=0.08), however 2-hour FFA levels are not
significantly different by frailty status. Median fasting leptin levels are similar by frailty status though
2-hour leptin levels are higher in frail versus non-frail women (15.8 +/- 18.6 versus 9.5 +/- 9.6;
p=0.68). Median fasting adiponectin levels are similar by frailty status; however, 2-hour adiponectin
levels are lower in frail versus non-frail women (16.6 +/- 15.8 versus 19.4 +/- 13.8, p=0.22). Median
fasting GLP-1 levels are similar by frailty status but 2-hour GLP-1 levels were lower in frail versus
non-frail women (4.7 +/- 1.8 versus 6.0 +/- 5.3, p=0.22). Similarly, fasting median IGF-1 levels were
lower in frail versus non-frail women (64.4 +/- 15.5 versus 70.1 +/- 26.5, p=0.22). In summary, frail
women have lower fasting and 2-hour ghrelin, higher fasting FFA, higher 2-hour leptin, lower 2-hour
adiponectin, lower 2-hour GLP-1, and lower fasting IGF-1 though we were not able to observe
significant associations for all these hormones.
In logistic regression analyses, we examined associations of frailty with free fatty acids, gut(ghrelin, GLP-1) and adipocyte-derived hormones (leptin, adiponectin) at 0, 30, 60, 120, and 180minutes after the 75-g glucose challenge. Frail versus nonfrail women were significantly more likely
to be in the lowest tertile of fasting (p=0.02) and 120-min ghrelin (p=0.03) after age and BMI
adjustment, with borderline significance for 180-min ghrelin (p=0.06) and integrated ghrelin areaunder-the-curve (p=0.06). No significant differences were found for other hormones. Our findings
suggest dysregulation of the orexigenic hormone ghrelin in the frailty syndrome.
These initial results support the use of a glucose challenge test to differentiate derangements in
metabolic hormones by frailty status. After further discussion, we decided not to run IGF-1 assays on
OGTT samples as this protein does not change much minute-to-minute. Instead, we will run
fructosamine, a marker of glucose metabolism that reflects changes in the past 2-3 weeks and is a
relatively good marker of post-prandial glucose elevations, on baseline samples and explore
differences by frailty status.
Publications/Abstracts/Grants:
Papers:
1) Relationship of glucose and insulin measurements from a oral glucose tolerance test with
muscle mass: Baltimore Longitudinal Study of Aging – epublished ahead of print in Feb 2011
in Journal of Gerontology: Medical Sciences. This study found that both fasting and postchallenge glucose and insulin measurements in the non-diabetic range were associated with
lower muscle mass in older adults, and that fasting glucose and the Matsuda index of insulin
sensitivity were the strongest predictors in Bayesian analysis.
2) Frailty status and altered glucose-insulin dynamics in older women: Women's Health and
Aging Studies II – submitted to Diabetes Care. This study in 73 older women without known
diabetes found that frailty was associated with higher post-challenge, but not fasting, glucose
and insulin levels compared to prefrail and frail women. The 2-hour glucose level was robust
even in sensitivity analyses excluding women with undiagnosed diabetes, suggesting clinical
meaningfulness to this testing abnormality.
Grants:
1) Glucose, Insulin and Muscle Loss - K23 Mentored Career Development Award submitted to
the NIDDK in February 2011. The proposed research will examine: 1) the association of high
glucose and high insulin levels with loss of muscle mass and strength over time both crosssectionally and longitudinally in large epidemiological cohorts (NHANES, BLSA); 2) explore
effects of an exercise intervention on the association of glucose metabolism, insulin sensitivity,
and improvements in muscle; and 3) the effect of an insulin sensitizer (pioglitazone) on
clinically assessable changes in muscle and potential underlying pathways in muscle
(mitochondrial dysfunction, protein degradation pathways) using muscle biopsy, and whether
these effects are age-dependent. Pioglitazone has been shown in animal models to be associated
with significant improvements in muscle mass. This work will inform future trials designed to
improve health and physical function in persons with diabetes as they age.
Abstracts:
1) The Frailty Syndrome and Glucose and Insulin Measurements from the Oral Glucose Tolerance
Test – accepted for poster presentation at the 71st American Diabetes Association Scientific
Sessions in June 2011. This abstract is based on the research submitted as part of manuscript #2
above.
2) Frailty and Hormonal Regulation of Energy Metabolism – submitted to Gerontology Society of
America as part of symposium on “Challenge Testing in Frailty”. This abstract is based on
research supported by the OAIC pilot core and found that lower ghrelin levels were associated
with frailty status.
3) Physical activity and glucose tolerance in older women - submitted to Gerontology Society of
America as part of symposium on “Determinants and Outcomes of Physical Inactivity: from
Built Environment to Human Physiology”. This abstract is based on research that found selfreported physical activity level was positively associated with glucose tolerance in older
women.
PES-3: Sevil Yasar, MD, PhD, “The renin-angiotensin system and physical and cognitive
frailty”: Age-related physical and cognitive disability and loss of function are becoming priorities in
public health. Frailty, which is considered synonymous with disability, is highly prevalent in old age
and is associated with increased morbidity and mortality. Although cognitive impairment is not
included in the definition of frailty, there is evidence that frailty can predate cognitive impairment, and
that frailty is associated with cognitive decline and impairment. Evidence suggests that the reninangiotensin system (RAS) plays a role in physical function. The ACE Insertion/Deletion DD
polymorphism genotype, which has higher ACE activity than II and ID genotype, may be associated
with worse physical performance and skeletal muscle function. Similarly, studies suggest that
alterations in components of the brain RAS, such as angiotensin II (Ang II), angiotensin III (Ang III),
angiotensin IV (Ang IV), and angiotensin converting enzyme (ACE), contribute to changes that can
lead to cognitive decline. There are currently no studies available evaluating possible associations
between blood levels of ACE and angiotensins and physically or cognitively impaired patients. Based
on previous findings, we hypothesize 1) that RAS is involved in physical and cognitive frailty, 2) that
elevated levels of Ang II and ACE are associated with worse performance on both physical and
cognitive measures, and that 3) elevated levels of Ang II and ACE are associated increased incidence
of physical and cognitive frailty. We will 1) evaluate cross-sectional associations between baseline
serum levels of Ang II and ACE, and specific components of physical and cognitive functions and 2)
evaluate longitudinal associations between baseline Ang II and ACE, and changes in trajectories of
specific components of physical and cognitive functions over 1 year recruiting participants from
Baltimore Experience Corps Study (BECS) Brain Health Study. We have three specific aims to test our
hypothesis: Specific Aim 1. Identify and describe the distributionof levels of Ang II and ACE, and
describe the associated sociodemographic characteristics in older, community-dwelling participants.
Specific Aim 2. Determine cross-sectional associations between baseline serum levels of Ang II and
ACE, and specific components of physical and cognitive functions. Specific Aim 3. Determine
longitudinal associations between baseline Ang II and ACE, and changes in trajectories of specific
components of physical and cognitive functions. The proposed study will be unique, since it will
evaluate associations between blood levels of both endogenous angiotensisn and related enzyme
activities in patients with physical and cognitive frailty and should allow us to 1) evaluate possible
associations between blood levels of ACE and Ang II and frailty, 2) better understand underlying
pharmacological mechanisms of frailty, 2) develop biomarkers and 3) develop targeted primary and
secondary preventive interventions. The experiments are relevant to the biological focus of the Older
American Independence Center (OAIC) because they capitalize on recent advances in RAS biology to
fill a major gap in our understanding of physical and cognitive frailty and they aim to facilitate the
discovery of new biomarkers and pharmacological therapies for frailty. In addition, this pilot project
will serve as the foundation for a NIH R01 grant for the planned investigators.
Updates / Results: Since 07/2010 a total of N=53 participants of the Baltimore Experience Corps Study
(BECS) Brain Health Study (PI: M. Carlson) have returned for an annual follow up visit. Of the 53
participants 14 have been excluded due to reported use of either angiotensin converting enzyme
inhibitor (ACE-I) or angiotensin receptor blockers (ARB) within the last 3 months (exclusion criteria).
At the annual follow-up visit, interim histories, standardized physical and cognitive exams, and
laboratory studies (serum was collected for measuring ACE and angiotensin levels and was stored in
freezers to measure Ang II levels). All participants gave informed consent to this study, which was
previously approved by the IRB of Johns Hopkins University. On 11/22/2010 plasma levels of ACE
were measured in N=39 participants in the Johns Hopkins Bayview Clinical Research Unit-Core
Laboratory (PI: N. Fedarko). On 01/03/2011 plasma levels of angiotensin were measured in N=39
participants in the Johns Hopkins Bayview Clinical Research Unit-Core Laboratory (PI: N. Fedarko).
On 02/15/2011 obtained data on demographics (age, gender), physiologic measures (vitals, weight,
height), physical (grip strength, gait speed test, chair stand test and cognitive function (Geriatric
Depression Scale, Folstein Mini Mental State Examination, Trail Making Test, Part A and B, Rey
Auditory Verbal Learning Test – immediate and delayed recall), and laboratory studies (ACE and
angiotensin II). On 02/22/2011, the investigator started data cleaning and addressing Specific Aim 1.
Until 2/25 additional N=3 were enrolled in the study increasing the total to N=42, and we are still open
for additional participants. Analyses, for cross-sectional associations between cognitive functions and
plasma levels of ACE and angiotensin II are currently be done, and will be presented at the next JHU
Pepper in May.
Publications/Abstracts/Grants:
Preparations are made for the next round of blood draw, which will enable us to evaluate associations
between changes of ACE and angiotensin II levels and cognitive and physical function. Preliminary
data from the Pepper Pilot Study is being used for a submission (06/2011) of NIH funded R21 grant in
order to support longitudinal data collection and analyses. Additionally, preparations are made to
measure angiotensin II levels in cerebrospinal fluid and evaluate for possible associations between
cognitive and physical function.
PES-4: Qian-Li Xue, PhD, “Effects of Inflammation, Hormonal Alteration and mTOR Signaling
in Modulating Age-related Declines in Muscle Strength” (funded April 2011)
Specific Aims: Aging is associated with the progressive loss of skeletal muscle mass and strength
referred to as sarcopenia, leading to significant adverse functional and clinical consequences in older
adults. Sarcopenia affects approximately 45% of persons aged 65 and older, accounting for 1.8% ($8.5
billion) of total health care expenditures in the US in 2000. Given rapid growth in the nation’s older
population, research to better understand the pathophysiology of age-related muscle weakness is of
substantial importance. Only thereby may targets and strategies to prevent and slow associated declines
in function, health status, and quality of life for older adults be identified. Converging lines of evidence
from human and animal studies suggest that multiple pathophysiologies may be implicated in the
development of muscle weakness1, 3 including oxidative stress, inflammation, hormonal change, and
malnutrition. However, research to date to characterize the etiology of age-related muscle weakness
has had two major limitations. First, most studies have been cross-sectional and correlative; therefore
causal relationships cannot be evidentially inferred. Second, previous studies have focused largely on
the influence of a single physiologic system/signaling pathway on muscle strength. It would seem risky
and even misleading to recommend preventive and treatment interventions based on isolated studies
targeting only an individual system, without a clear understanding of the interrelationships among
multiple physiologic systems and their age-related functional declines. So far, the interactions among
the hypothesized mechanisms have not been evaluated longitudinally.
Building on our earlier work on cross-sectional associations of inflammation and endocrine
dysregulation with muscle strength and frailty in older adults, and the new evidence of antiinflammatory and life-extending effects of the Mammalian Target of Rapamycin (mTOR) inhibitor
rapamycin in mice8, our hypotheses are that (H1) increasing inflammation and decreasing
anabolic hormone levels independently and synergistically contribute to age-related decline in
muscle strength; and (H2) rapamycin ameliorates decline in muscle strength by suppression of
inflammation, and its effects can be enhanced in combination with growth hormone
supplementation and aerobic exercise. We propose to evaluate these hypotheses by conducting a
pilot trial of a multi-faceted intervention in rats selectively bred for low aerobic running capacity [low
capacity runners (LCR)]. The specific aims are to:
1) evaluate the separate and joint effects of age-related changes in biomarkers of inflammation
[Interleukin-6 (IL-6), Tumor Necrosis factor-α (TNF-α)], and anabolic hormone [Insulin-like
growth factor-1 (IGF-1)] on change in muscle strength in LCR rats.
2) pilot test the efficacy of combined treatment with aerobic exercise, rapamycin, and recombinant
rat GH (rrGH) in ameliorating age-related decline in muscle strength in LCR rats. To
accomplish this, we will conduct a 1-year trial with one control arm receiving no treatment and
two treatment arms (i.e. rapamycin alone, aerobic exercise+rapamycin+rrGH) for LCR.
The proposed research will provide the first laboratory evidence on the modulating effects of mTOR
on inflammation and anabolic hormones. The pilot will generate preliminary data that could be used to
strengthen future grant applications to more definitively assess the efficacy of a combined exercise,
rapamycin, and growth hormone intervention on age-related progressive loss of muscle strength in
humans.
PES-5: Ronald D. Cohn, MD, “Role of Increased TGFbeta signaling in age-related muscle loss.”
The work of Dr. Cohn’s Pilot study, which was funded in grant year 7 (2009-2010), has continued
through a diversity supplement to Ms. Tyesha Burks, Dr. Cohn’s graduate student. Details on progress
are provided below in section II.F Diversity Supplement Award to Ms. Tyesha Burks
(3P30AG021334-08S1). Most notably, Dr. Cohn, Ms. Burks and colleagues recently published their
findings in the journal, Science Translational Medicine: Burks TN, Andres-Mateo, E. Marx R, Mejias
R. Van Erp C, Simmers JL, Walston JD, Ward CW, Cohn RD. Losartan restores skeletal muscle
remodeling and protects against disuse atrophy in sarcopenia. Sci Transl Med. 2011 May
11;3(82):82ra37. PMID:21562229.
Year 8 Small Pilot/Exploratory Studies (SPES):
SPES-1: Sean Leng, MD, PhD. This small Pilot was funded in May 2010. Funds have been utilized
for: cytokine measurements, phenotypic and functional studies of t-cells and monocytes /
macgrophages, and mitochondrial functional studies.
Project Overview: The objective of this small pilot grant is to help to develop pilot data demonstrating
LCR (low capacity runner) rats as a useful rat model to study human frailty for an R01 grant proposal
for an RFA “Development and Characterization of Animal Models for Aging Research” (PA-10-014)
from the NIA. The LCR and HCR (high capacity runner) rat model was initially introduced to the PI
(Dr. Leng) in 2007 at a national conference on human healthspan sponsored by the National
Academies of Science and Engineering and Institute of Medicine. Drs. Leng and Koch subsequently
obtained a pilot grant from the University of Michigan Pepper Center on the development of LCR rat
model for studying human frailty. With this collaborative pilot funding, we were able to develop data
on serum cytokine profile data of the LCR and HCR rats which have been submitted for presentation at
2010 GSA meeting 17 and included in a manuscript 4. In addition, we have obtained 28 animals in 4
groups: young LCR (7), young HCR (7), old LCR (7), and old HCR (7) rats. Meanwhile, Dr. Peter
Abadir, a junior faculty in our Biology of Frailty group who has expertise in measuring cytokines and
other factors in local tissues in live rats through microdialysis, will evaluate local cytokine milieu in
these animals. We have purchased the microdialysis equipment for these experiments. Dr. Abadir has
also developed skills in measuring mitochondrial function (using the Seahorse technology) in mouse
tissue which will be instrumental to this project. In addition, Dr. Huifen Li, a research associated in Dr.
Leng’s lab with expertise in immune studies in mouse and rat, will conduct T-cell phenotype analyses.
With the availability of these unique LCR and HCR rats and expertise in our study group, the specific
aims to further demonstrate LCR rats as a useful rat model for human frailty are:
• Aim 1: To conduct further phenotypic characterization of the LCR and HCR rats. Our
hypothesis is that the HCR rats have the phenotypic characteristics that mimic human frailty.
Based on our experience in the study of IL-10 knockout mice18, we measure and compare grip
strength by Grip Strength Meter, balance and gait by Rotorod, physical activity by direct
observation, and weight.
• Aim 2: To measure and compare cytokine milieu in the skeletal muscle tissue in anesthetized
LCR and HCR rats through microdialysis and correlate it with serum cytokine levels. This is
critically important because we do not have routine access to muscle tissue for evaluating local
cytokine milieu. We have an approved animal study protocol (RA08M45) for the proposed
studies in Aims 1-4.
• Aim 3: To measure and compare phenotypes and function of T-cells and
monocytes/macrophages in LCR and HCR rats, including T-cell phenotypes (CD3, CD4, and
CD8) and monocyte/macrophage (ED1/CD68) and their ex vivo production of proinflammatory cytokines upon PHA (for T cells) and LPS stimulation. We isolate peripheral
mononuclear cells from the blood and splenocytes and conduct flow cytometry analysis of their
phenotypic characteristics by surface staining of above CD markers and intracellular staining of
IL-6 and IP-10/CXCL10 production. We will also purify T cells by CD3 or ED1/CD68
magnetic column for ex vivo stimulation experiments. These immune studies are based on our
published data in human frailty studies6-7, 9-10, 12. Cytokines will be measured using
multiplex ELISA (for Aims 2-3) 19.
• Aim 4: To measure and compare mitochondrial function in LCR and HCR rats. We isolate
mitochondria from the fresh skeletal muscle tissue and measure their function by the Seahorse
technology. These studies are built on the ongoing experiences of Dr. Peter Abadir.
This small pilot grant bridges the following specific funding gaps: a) expenses related to cytokine
measurements (Aims 2-3); b) costs for flow cytometry analysis including monoclonal antibodies (Aim
3); and c) expenses for mitochondrial studies (Aim 4). With this help, we expect to accomplish the
proposed studies and develop the R01 grant proposal for an upcoming deadline.
SPES-2: Cindy Roy, PhD. This small Pilot was funded in May 2010. Funds have been utilized for:
Sodium Salicylate Diet, Sodium Salicylate, Placebo Diet, Mouse Cages (6), Complete Blood Count,
ELISA Kits (multiplex analysis), Technical effort (5%), and Consumables.
Project Overview: NF-B, the primary regulator of the inflammatoryresponse, is increasingly
recognized as influential in the biological processes that promote declining health status with age.
Sodium salicylate is a potent inhibitor of NF-B transcriptional activity. Dr. Roy proposed to test the
hypothesis that sodium salicylate treatment will prevent the observed increase in inflammation and
decline of physical performance measures and erythropoiesis in frail (il-10 deficient) mice that have
increased NF-B transcriptional activity. This study aimed to determine whether 3 months of sodium
salicylate treatment:
1) Reduces inflammatory markers, IL-6, KC, MCP-1
2) Prevents the decline of activity, grip strength and rotorod performance
3) Prevents the decline of hemoglobin production and erythroid maturation
In 12 and 18 month old, sodium salicylate-fed frail female mice compared to placebo-fed, age- and
gender-matched frail mice.
This small pilot project was designed to generate preliminary data for an RO1 application that will be
submitted to the NIDDK in October 2010. At minimum, it will generate sufficient data for sample size
calculation. Dr. Roy and colleagues cannot make estimates of how quickly salicylate will reduce
inflammation. At best, it will show protection from anemia. Pilot funds will support a targeted, preclinical intervention in frail mice currently available in the Roy mouse colony. To date, there have
been few attempts to intervene on frailty and its related phenotypic traits of muscle weakness and
anemia. This study will test a relatively safe agent for its ability to improve traits which are clearly
associated with frailty in mice and humans.
Results/Updates: The investigator has observed that aged IL-10-deficient (frail) mice have an anemia
consistent with anemia of inflammation. Dr. Roy and colleagues have treated 20 IL-10-deficient mice
with either sodium salicylate supplemented diet or placebo. Of the 20 mice, 6 (3 salicylate, 3 placebo)
were 20 months of age. Too many of these died before their planned sacrifice at 22 months. The
remaining 14 mice were started on the diet at 12 months of age. The investigators were only able to
treat 5 in each group (5 salicylate, 5 placebo) for 5 months before the diet expired after 6 months. An
additional 2 mice in each group (2 salicylate, 2 placebo) were on the diet for 3 months due to later birth
dates. In comparing the 5 salicylate-treated mice versus 5 placebo-treated mice, they did not find a
statistically significant increase in hemoglobin or erythrocyte number, but the curve was a quadratic,
with a peak after one month on the diet.
Dr. Roy and colleagues have recently found that IL-10-deficient mice are markedly iron-deficient (76
g/g liver versus 180 g/g liver in age- and sex-matched controls, p=0.008), which may explain the
poor hemoglobin response on the salicylate diet. Quantitative real-time PCR (qPCR) for expression of
hepcidin, an iron regulatory hormone, was normal to low in several mice, consistent with iron
deficiency. In the future, they may have to supplement both groups with iron to assess a response to
salicylates.
Interestingly, there was a statistically significant increase in grip strength for the salicylate group upon
cross-sectional analysis of the data at 17 months of age, though no significant changes in activity,
rotorod performance or erythroid parameters were identified. Serum IL-6 concentrations decreased
from 60 pg/mL in the placebo group to 36 pg/mL in the salicylate-treated group, though this result was
not statistically significant. There was no discernable difference in KC concentration. MCP-1 could not
be tested on the 7-plex pro-inflammatory cytokine ELISA that was used to conserve small amounts of
serum. Serum erythropoietin concentration is pending.
Dr. Roy is actively working toward testing this hypothesis in anemic older adults through her
participation in the Partnership for Anemia Clinical and Translational Trials in the Elderly (PACTTE),
an NIA-sponsored, UO1 consortium. As a member of the consortium, Dr. Roy has participated in the
development of a clinical trial acetylated salicylate that is known to inhibit NFB.
•
•
Paper Development: Dr. Roy and colleagues are developing a brief report characterizing the
mixed iron deficient anemia and anemia of inflammation in frail (il-10-deficient) mice.
Grant Development: The RO1 application submitted to NIDDK in October 2010 to develop
pre-clinical trials for the use of non-acetylated salicylates for the treatment of anemia in aged
and chronic disease populations was unscored. After review of summary statements with Dr.
Walston, and publication of the two papers above, Dr. Roy will revise and resubmit.
SPES-3: Arabella Leet, MD, Peter Abadir, MD. This small Pilot was funded in September 2010.
Funds have been utilized for: purchase of mice and for reagents and service fees for immune-electron
microscopy, immunehisto-chemistry, western blotting, different antibodies and for µCT. Additional
supplies that are needed include animal sacrifice, disposable pipette tips and gloves, laboratory
reagents for processing and storage.
Project Overview: Hypothesis: Losartan treatment improves the rate of tibia fracture healing in older
mice compared to age matched mice with similar fracture and no Losartan treatment.
Specific Aim 1: To evaluate the effects of Losartan treatment on rate of fracture healing. Specifically
we aim to conduct a pilot study comparing fracture healing in young and aged mice both at base line
and when treated with Losartan. The mouse population to be studied will consist of 10 young (4 wks)
C57Bl6 female mice and 10 older (52weeks) C57Bl6 female mice given the AT1R blocking agent
Losartan (3) and 10 young (4 weeks) and 10 older (52weeks) C57Bl6 kept in identical conditions but
not given Losartan. All mice will undergo facial bleeding and serum will be stored for later
measurement of cytokines and angiotensin and renin via an ELISA multiplex. Mice will then be given
Losartan mixed in their water bottles or water (control) for 2 weeks.
After pre-treatment, a closed tibia fracture will be performed using previously established and ACUC
approved protocols (MO03M375) and mice will be followed for either 2-3 weeks (soft callus group) or
4-6 weeks (hard callus group). At each of these two time points, five mice from each group will be
sacrificed and the fractured and nonfractured tibia will be removed for histology to include analysis of
cartilage content (safranin O); TRAP staining for osteoclastic activity and picrossirus red staining in
polarized colors for altered collagen content. All histology will be conducted by Dr. Edward McCarthy
in the department of Pathology at Johns Hopkins Hospital. Images will be compared for differences
qualitatively with quantification of callus via µ CT. µCT will be done in the Small Animal Imaging
Resource Program; Dr. Benjamin Tsui will be performing all the imaging studies in the study.
µ CT imaging will be used to determine early stage callus size, rate of mineralization and canal
remodeling comparing age (young and old) and treatment (Losartan and saline) groups. µ CT will be
the primary endpoint for power. Using graph pad statmate 2 for statistical analysis, using 10 animals
per group and values from the literature (with the mean difference .52 and a standard deviation of .20
for density and a mean of .56 and standard deviation of .23 for mass) we conclude that our experiment
has a 90% power to detect a difference between means of just 0.31 with a significance level (alpha) of
0.05 (two-tailed). The serum from the mice will again be sampled at these time points and stored for
future measures of cytokines and RAS related serum markers.
Specific Aim 2: To demonstrate changes in tissue specific markers of bone healing in response to
aging and to long term treatment with the AT1R blocker Losartan. We will compare changes in gene
expression and protein synthesis in bone cells from the four groups of mice described above. Using
RT-PCR, measurements of AT1R and AT2R genes will be performed as well as measurements of bone
specific tissue markers such as bone sialoprotein, alkaline phosphotase or osteocalcin.
SPES-4: Sameera Talegawkar, PhD. This small Pilot was funded in October 2010. Funds have
been utilized for: personnel (graduate research assistant) and other expenses (administrative costs).
Project Overview:
The specific aims are to determine whether in a cohort of older men and women, a greater adherence to
a Mediterranean type of diet: (1) is cross-sectionally associated with presence of frailty at baseline. (2)
predicts the development of frailty after a follow-up of 6-y from baseline. To address these aims, Dr.
Talegawkar assesses the adherence to a Mediterranean diet in 1270 adults, 65 years and older, who
participated in the InCHIANTI study, a population-based study conducted in two small towns, Greve
in Chianti and Bagno a Ripoli, in Tuscany, Italy. Adherence to a Mediterranean diet is assessed using
the Mediterranean Diet Score (MDS) proposed by Trichoupoulou et.al. using dietary data that have
been collected in the cohort at enrollment. Both, cross-sectional and longitudinal relationships between
MDS and frailty are examined. Frailty is based on the definition of Fried et.al. modified by Bartali
et.al. for the InCHIANTI cohort. Dr. Talegawkar and colleagues expect that in the InCHIANTI cohort,
a higher Mediterranean Diet Score at baseline (indicating higher conformity to a Mediterranean-type
diet) is inversely associated with frailty at baseline, and will be associated with a lower risk of
development of frailty after a follow-up of 6 years.
Results/Updates:
This proposal was approved by the OAIC investigators on the 21st of October 2010. Since then, the
Mediterranean Diet Score variable has been derived using the dietary data for the InCHIANTI cohort.
Dr. Talegawkar completed analysis examining its validity using nutrient biomarkers and is now
nearing completion in deriving the frailty variable for the 6-year follow-up. She is currently finishing
up the requested changes for a related manuscript (MDS and cognition/biomarkers), which reflected
the initial project that was proposed and then modified based on reviewer comments to include frailty
as an outcome.
The work on the frailty outcome commenced in late January 2011, after a brief delay due to identifying
a data analyst. The analyses (creation of the frailty variables as well regression analyses) for the frailty
outcome were completed in early April. Dr. Talegawkar and her analyst are working with Karen
Bandeen-Roche and the OAIC Biostatistics Core to finalize our analyses, and complete the project by
the end of May.
SPES-5: Franco D’Alessio, MD. This small Pilot was funded in November 2010. Funds have been
utilized for: mice and Adoptive transfer experiments.
Project Overview: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) cause
severe lung inflammation and refractory hypoxemia and associated high mortality, imposing a
substantial burden on the health care system. In contrast to studies of early pathogenesis, relatively
little is known about the processes leading to resolution of lung inflammation and injury. The
incidence and mortality of ALI are significantly increased by aging (20- and 3-fold respectively).
Although age-associated studies that increase susceptibility in older hosts have been described in
animal models of ALI, mechanisms underlying these differences are not defined. Understanding age-
related differences in ALI and its repair are critical to translating therapeutics to an increasingly aged
population.
Specific Aims:
We hypothesize that aging-related changes in lung immune responses allow unremitting inflammation
after Acute Lung injury (ALI), thus negatively impacting lung repair. We anticipate that targeting
altered aging-induced immune responses after the onset of ALI may prove useful as therapy to
accelerate resolution in older patients. We propose the following specific aims (SA):
1. To determine the impact of aging on alveolar Regulatory T cells-mediated resolution of ALI. Both
in vivo and in vitro studies will be used to evaluate the effect of aging on Treg phenotype and function.
2. To examine mechanisms by which aging modulates alveolar macrophage co-signaling molecules in
resolving lung injury. Using in vivo and in vitro approaches, we will determine the effect of aging on
co-signaling molecules at different stages of injury and resolution using multi-color flow cytometry
and in vivo antibody blockade.
Studies and Results
Over the past 3 months we have made significant progress on assessing mechanism underlying agerelated dysregulated lung immune responses that contribute to unremitting lung inflammation.
Aim 1
We have generated compelling data to support that aging alters Regulatory T cells (Treg) phenotype,
proliferation and function after ALI. When using young (12 weeks) and old (1.5 years) WT mice after
i.t. LPS, old animals had increased mortality, persistent alveolar protein and elevated cell counts out to
7 days later after injury (not shown). Given our previously described critical role for Tregs in
orchestrating lung repair and resolution of lung inflammation we hypothesize that Aging altered Tregs
after ALI. Multicolor flow cytometry revealed marked reduction in alveolar Treg numbers and
suppressive proteins in Tregs 7 days after i.t. LPS in old animals compared to young. Using a live
bacteria model of ALI, after 5 days of i.t. Pseudomonas aeruginosa (PA-01 strain), Tregs numbers and
proliferation (ki-67 expression) was markedly reduced in different compartments in old compared to
young animals, particularly in the alveolar space. To assess a functional impact of decreased number of
Tregs in old mice after ALI, we performed adoptive transfer of Tregs isolated from young and old
mice into injured old animals. Lung H-E sections revealed that supplementing young Tregs into old
animals could rescue the phenotype of unremitting lung inflammation. In contrast, transfer of
supplemental old Tregs failed to improved outcomes.
Aim 2
We have preliminary data supporting the role of co-signalling molecule CD86 in the regulation of lung
inflammation. We immunophenotype alveolar macrophages in young and old mice after i.t. LPS and
found sustained expression of macrophage CD86 in old animals compared to young 7 days after ALI.
To test a functional role for sustained expression of CD86 in old injured mice, we used antibodymediated blockade of CD86 and found accelerated resolution of lung inflammation in old mice treated
with anti0CD86 antibodies compared to isotype Ab-treated.
Significance:
The proportion of individuals above 60 years will increase from 10 to 22% by 2050, creating a
significant challenge for the health community. ALI/ARDS produces tremendous morbidity and
mortality, particularly in the elderly, but to present therapy principally takes the form of supportive
care. Longstanding focus on determinants of injury has limited a broader consideration of determinants
of resolution. Resolution of inflammation is an active process with distinct mechanisms and targets for
therapy. Our data indicates that aging alters lung immune responses critical to resolution of ALI. With
this novel line of investigation, we hope to facilitate identification of new targets for therapy of this
prevalent and often fatal syndrome.
Plans:
Our plans over the next year are to continue experiments to continue examining age-related
dysregulated innate and adaptive lung immune responses after lung injury. We have already made
significant findings and anticipate several manuscripts, scientific meeting presentations and a R01
proposal generated with this line of investigation.
Publications/Abstracts:
D’Alessio FR, Garibaldi BT, Mock JR, Files DC, Eto Y, Aggarwal NR, King LS. Age-Dependent
Impairment in Lung Injury Repair due to Sustained Alveolar Macrophage CD86 Expression. In
preparation. Abstract will be also presented at AJRCC. Denver, May 2011.
SPES-6: John Harmon, MD. This small Pilot was funded in February 2011. Funds have been
utilized for: mouse and caging fees.
Project Overview:
Hypothesis: Intravenous injection of autologous Circulating Angiogenic Cells (CACs) expanded in
tissue culture and activated by Hypoxia Inducible Factor 1 alpha, will correct the impairment in wound
healing seen in elderly mice.
Specific Aims: To assess the rate of wound healing in older (18 month old) mice treated with
autologous CACs. We harvest these cells from the bone marrow, culture them under endothelial
conditions, and call them bone marrow derived angiogenic cells t(BMDACs). To activate these cells
we will utilize a double HIF-1 strategy. This will be done by first culturing the cells with DMOG to
increase HIF-1 levels, and also directly with a DNA plasmid that will express a constitutively active
form of HIF-1.
Methods: 18 month old C57 mice from the NIA-NIH colony will be purchased from NIA aging mouse
colony. Each mouse will have an 8 mm excisional wound made on the dorsum as per standard ACUC
approved protocol.
Experimental Groups:
1) BMDAC Rx vs vehicle N=12 per group Total 24
2) BMDAC+DMOG vs vehicle N=12 per group Total 24
3) BMDAC+DMOG+ HIF to wound vs vehicle N=12 per group Total 24
Two iterations of each experiment: 144 mice total. Assessment of wound healing: Computerized
Plannimetry for wound closure assessment days 0, 3, 7, 14, and 21. Wound Harvest: Day 21 Tissue
samples will be collected from the wound site and from normal skin away from the wound site,
between the shoulder blades, immediately below the neck. One half of each sample will be snap frozen
and stored at -80 degrees Celsius. The other half will be fixed in formalin for histologic exam.
Translational Potential: If successful in frail older mice, this technology could be expanded to human
subjects. Given that the stem cells are autologous, they can be derived from human subjects and grown
in culture with DMOG. Dr. Harmon already has begun work on translational projects through a related
biotechnology startup company named Canton Biotechnologies where he has the capacity to rapidly
move forward promising pre-clinical studies. For example, Canton Biotechnologies is currently
working with the HIF-1 plasmid DNA delivery system for improving healing of diabetic foot ulcers.
This project could be translated for a variety of wound situations including decubitus ulcers and burns
in the elderly where current outcomes are particularly poor.
Results/Updates:
As of April 2011, an ACUC application has been approved to commence with the work. Aged
animals are on order from the NIH NIA. Notably, a project from Dr. Harmon’s lab using BMDACs
to track homing of bone marrow stem cells to wounds in aged animals was selected as the Best Paper
of the Year by the Wound Healing Society. It was presented April 2011 in Dallas at the Annual
Meeting of the WHS.
II.E.
LEADERSHIP ADMINISTRATIVE CORE
Jeremy Walston, M.D., Core Leader
410-550-1003
410-550-2513 FAX
[email protected]
Karen Bandeen-Roche, Ph.D., Co-Core Leader
410-955-3067
410-955-0958 FAX
[email protected]
Brian Buta, Administrator
410-502-3412
410-614-9625 FAX
[email protected]
The Leadership/Administrative Core spearheads the vision for the science of frailty and its translation
in this OAIC. It leads in identifying the next generation of research on frailty that should be created,
supports research planning, recruitment of investigators, and the setting of goals and benchmarks. It
also administrates the OAIC and its Cores and creates visibility for the accomplishments of the OAIC.
Led by the Co-Principal Investigators of this OAIC, in collaboration with the leaders of all other OAIC
Cores and supported by administrative staff, the roles and responsibilities of this LAC include the
provision of essential leadership in planning, integrating, sustaining and monitoring OAIC operations,
the organization and evaluation of all elements of this OAIC, and reporting. Its goals are to ensure the
conduct of these OAIC functions within a broader goal of helping recruit, initiate and nurture creation
of a critical mass of investigators dedicated to advancing discoveries essential to prevention and
treatment of frailty in older adults, and supporting the creation of innovative, high impact research to
this end. The overall goals of workforce development and support of research are to translate the
results of OAIC-supported work into new treatments to enhance independence in older Americans, and
creation of a new generation of research leaders in the field.
To these ends, the specific aims of the Leadership and Administrative Core (LAC) are to:
1. Provide leadership and organization that will stimulate and sustain the development of innovative
research that will lead to new treatments and prevention of frailty in older adults, facilitate translation
between basic and clinical research on frailty, and ensure effective, high impact utilization of each of
the cores within the Center.
2. Identify and attract the next generation of research leaders to obtain training and career development
and conduct cutting edge research that will advance the field, and to develop innovative and
sustainable careers in this field. To this end, this LAC is responsible for visibility for research on
frailty at our institution and implementing the recruitment activities, based on leadership decisions
about target areas for scientific and methodologic development.
3. Provide the intellectual capital and structures for leadership and administration and manage the Core
processes of the OAIC.
4. Organize an independent review panel for proposed Developmental projects, Pilot and Exploratory
Studies, and for the selection of specific junior faculty to receive salary support from the Research
Career Development Core; and organize yearly review by an External Advisory Committee of progress
toward OAIC goals.
5. Preparation of annual reports for non-competing renewal applications, and administrative documents
as needed. This will include the report from the External Advisory Board.
6. Organize and conduct annual retreats, research in progress and research planning meetings to propel
the science and career development of those who participate in the OAIC.
7. Participate in annual national scientific meeting of OAICs.
During this reporting period, the Leadership Administrative Core convened the OAIC Leadership
Council at least monthly to establish, propel, and review overall scientific goals and benchmarks of all
cores, and the training and faculty development goals from the RCDC and Pilot Cores, as well as
ongoing Core progress and accomplishments, and of the supported faculty.
Specifically, the accomplishments of this Core include:
Specific Aim 1:
 The Leadership Council convened for a monthly meeting each month during the past year. In
addition, Drs. Walston and Bandeen-Roche continue to meet on frequent basis with the OAIC
administrator between each Leadership Council meetings.
- Leadership representation from the Department of Medicine has continued in monthly
meetings. Myron Weisfeldt, M.D., Professor and Director, Johns Hopkins Department of
Medicine, joined the council in April, 2008 and has participated faithfully and fully since
then and continues to serve.
- In addition to activities reported below, the Leadership Council continues the effective,
high impact utilization of each of the cores within the Center through the implementation of
a small grants program. Three researchers have been supported during this reporting
period, with two additional proposals currently under review. Details on the investigators,
science at issue and usage of the resources provided may be found in the report for our Pilot
Core.
 The Leadership Council has reviewed, and spearheaded the OAIC portion of, a full update of the
Johns Hopkins Center on Aging and Health Website: please see
http://www.jhsph.edu/agingandhealth/oaic/
 The Leadership Council has established as an unsurpassed priority the development of
interventions to prevent or ameliorate frailty and its ramifications for loss of health and
independence among older adults. To the end of this priority:
- the evaluation of targets for intervention has been an ongoing agenda topic within its
monthly meetings. Inflammatory processes, nutrition, exercise and energy were among the
targets considered. Based on the evidence base as well as feasibility considerations, the
Council opted to pursue Vitamin D as an initial target. The IRB for the proposal has been
approved. Details are provided in the RCDC report. Further targeted biological pathways
include the inflammatory and the renin-angiotensin systems, both areas of active biological
investigation within this OAIC.
Specific Aim 2:
 In the past year, the LAC of this OAIC has made key linkages with investigators in departments
where connections and collaborations have been limited or non-existent in the past. For example,
Dr. Jiou Wang from the Department of Biochemistry and Molecular Biology in the School of
Public Health received Genetics Core developmental project funding; Dr. Frank Lin from the
Department of Otology, Neurotology, and Skull Base Surgery received RCDC funding and Dr.
Yuri Argawal from the same Department was awarded a pilot study; Dr. Aliaksei Pustavoitau from
the Department of Anesthesia and Critical Care Medicine received RCDC funding; and small Pilot
Projects were awarded to Drs. John Harmon (Surgery, Bayview Medical Campus), Arabella Leet
(Orthopedic Surgery) and Sameera Talegawkar (Department of International Health).
 The leadership council and the PIs have further developed connections with individuals in the
Molecular Genetics programs at JHU by facilitating the recent award of a diversity supplement to
Tyesha Burks, a graduate student who works closely with Ronald Cohn, a former Pilot Core
awardee. Ms. Burks is receiving ongoing mentorship from core leaders around key issues in frailty
and aging research from Drs. Walston and Bandeen-Roche, and is participating in all OAIC
activities for junior faculty and other trainees. She has also presented her work at OAIC national
meetings. Her efforts have very recently led to the acceptance of a very high profile manuscript
highlighting her work on the renin-angiotensin system in skeletal muscle in the journal Science
Translation.
 In order to further increase the local and national visibility of our OAIC, the leadership has
instituted an institution-wide Aging Research Initiative that aims to use the OAIC model of frailty
research interdisciplinary collaboration to facilitate cutting edge frailty research to other Hopkins
campuses and Departments that have not been traditionally represented on the medical campus.
Organizational meetings with the Deans of Medicine, Nursing, Public Health, and Arts and
Sciences have already taken place, as well as ongoing conversations with the President of the
University and the Provost. This planning process should enable the establishment of this initiative
during calendar year 2011. These activities will further the OAIC visibility across the Johns
Hopkins Institutions and further attract some of the brightest young scholars to this field of
investigation.


The OAIC continues to interact extensively with the leadership of the University of Maryland
OAIC as described in more detail below. This has allowed additional regional visibility.
The Leadership Council sponsored and implemented a quarterly seminar series of invited scientific
presentations, including a presentation by NIA Director, Dr. Richard Hodes. Those occurring in
the 2010-2011 academic year are listed as follows:
- June 16, 2010: Leon Flicker, Ph.D., Professor of Geriatric Medicine at the University of
Western Australia. Dr. Flicker was a visiting professor at the Center on Aging and Health
during the month of June.
-
-
-
-
Tuesday, September 21, 3:30-5:00PM: Arnold Mitnitski, Ph.D., Professor in the
Department of Medicine at Dalhousie University. Presentation topic: "Measuring individual
and population aging: a deficit accumulation approach." Jointly sponsored with the JHSPH
Department of Biostatistics.
Monday, October 25. 2010: Richard Hodes, M.D., Director, National Institute on Aging.
Presentation topic: Comparative Effectiveness Research in Geriatrics and Gerontology.
December 7, 2010: Knut Wittkowski, Ph.D., Biometrician and Senior Research Associate at
the Rockefeller University. Presentation topic: “µGWAS on a Grid Enabling Small
Sample Screening for Common Complex Conditions.” Jointly sponsored with the JHSPH
Department of Biostatistics.
Wednesday, March 9, 2011: Dr. Karin Wolf-Ostermann, Professor in Empirical Social and
Nursing Research from Alice Salomon University of Applied Sciences in Berlin, Germany,
visiting faculty at the JHU School of Nursing. Presentation topic: “Shared-Housing
Arrangements for People with Dementia in Berlin, Germany: Residents & Caregivers."
Wednesday April 20, 2011: Thomas Glass, Ph.D., Associate Professor in the Department of
Epidemiology at the Johns Hopkins School of Public Health. Presentation topic: Wearable
Computing in Epidemiology: Predicting Activity Type from Accelerometer Data. Jointly
sponsored with the JHSPH Department of Biostatistics.
Specific Aim 3:
 In accordance with timetable set forth in the Leadership and Administrative Core proposal for the
current cycle, the Leadership Council provided oversight of all Cores’ progress. Specifically:
o Each Core presented progress, and was given feedback, at a monthly Leadership Council
meeting.
o The Leadership Council reviewed the progress of projects supported by the Research Cores
and Pepper funds through presentations of work in progress by all junior faculty supported
by our OAIC, and facilitated individual meetings for junior faculty with senior
investigators.
o The Leadership Council continued quarterly progress reports for all supported investigators.
o Specificity of progress expectations for faculty with supported projects was increased to
make continued support contingent on acceptable progress made at interim benchmarks.
 Budgetary oversight was provided. Carryover funds were successfully acquired, and budget for
2010-2011 has been established. External funding opportunities were sought and successfully
obtained.
Specific Aim 4:
 The Leadership Council has successfully implemented the review and award process for new pilot
studies and new junior faculty. Though some of the current awards are continuations from last
year’s grant cycle, it became necessary to seek out new RCDC and Pilot investigators for the next
grant cycle (2010-2011) due to the success of several of our appointees in earning K awards. We
successfully identified, implemented review for, and granted awards to RCDC awardees Frank Lin,
MD, Peter Abadir, MD, Devon Dobrosielski, PhD, and Aliaksei Pustavoitau, MD; and Pilot Core
awardees Yuri Agrawal, MD, Rita Kalyani, MD, Sevil Yasar, MD, PhD, and Qian-Li Xue, PhD.
These projects have commenced during this reporting period, and details are provided in the core
sections later in this report. In brief, our awarding process specifically includes:
-

Targeting of junior faculty and departments/programs with relevant scientific expertise
Distribution and advertisement of Request for Proposals via Center website, University
internet broadcast systems, and Department Chairs and Professors
- Receipt of scientific applications to the Center Administrator
- Review by an internal panel consisting of Core Leaders and Directors, and facilitated by
the Center Administrator
- Selection of semi-finalists by the internal panel
- Review by external reviewers, facilitated by the Center Administrator
- Announcement of awards to finalists by the Center Director
- The External Advisory Board (EAB) meeting was held on August 30, 2010. The EAB
consists of Joan Bailey Wilson, PhD, Harvey Cohen, MD, Deborah Dawson, PhD, ScM,
Luigi Ferrucci, MD, PhD, Kenneth Rockwood, MD, FRCPC. All have relevant expertise
in aging/frailty research or biostatistics.
This was the seventh meeting of the EAB. For this meeting:
- Our most recent progress report was sent to each EAB member along with a review form
to obtain their comments and recommendations on each section of the report. In this way,
Board Members could thoroughly review our progress while allowing us to delimit the
amount of meeting time devoted to de facto reporting.
- These meetings were designed to provide for ample interaction with EAB members and to
engage them to meaningful discussion, provision of recommendations and guidance to
Junior Faculty, and advising the Center’s overall goals, progress and direction. To this
end, the meeting included presentations of the center’s resource cores (Biostatistics and
Genetics), presentations by newly appointed Genetics Core Development Project faculty
and RCDC-supported faculty, presentation on the center’s Pilot Core and small pilots
program, and a presentation and scientific discussion on Biology of Frailty initiatives at
the center. We deemed the format to have accomplished its goal.
Specific Aim 5:
 Final report and recommendations of each EAB meeting were subsequently sent to the NIA
Program officer. Dr. Basil Eldadah.
 All needed administrative reports (including non-competing progress report for Year 7) have been
prepared and submitted.
Specific Aim 6:
 Our PIs and administrator participate regularly in monthly OAIC planning calls.
 Members of the Genetics core have played a leading role in national consortiums that were formed
to study aging and frailty related phenotypes in genome wide association studies and in very large
candidate gene studies. Our investigators have led groups studying muscle strength decline,
frailty, and inflammatory phenotypes and have developed a symposium that was submitted for
review for the Annual Meeting of the Gerontological Society of America. If accepted, that
symposium will be presented in Boston in November of 2011.
 Over the past year, our leadership and that of the University of Maryland OAIC have worked
together on initiatives by which we might leverage our complementary strengths and foci to enrich
the research environment for scholars associated with our OAICs, particularly our junior

colleagues. These discussions have led to individual networking connections, joint participation
in the annual JHU Research on Aging Showcase poster competition for graduate students,
postdoctoral fellows and junior faculty, and two Jointly-Sponsored Symposia presented
collaboratively by our Biostatistics Cores. The first symposium on clinical and comparative
effectiveness research was held on May 24, 2010 at University of Maryland-Baltimore, and the
second symposium on longitudinal data analysis was held on December 6, 2010 at Johns Hopkins
Medical Campus (see Biostatistics Core report).
During this grant cycle, a JHU OAIC collaboration-building project, known as the Pepper
Scholars Program, held ongoing monthly research-in-progress sessions that allow for OAICsupported investigator interaction and discourse, along with progress updates and access to
mentors and methodological experts. The program’s research-in-progress centerpiece is bolstered
by an online collaboration tool, an ongoing seminar series, grant review sessions, and research
facilitation by the center administrator on this effort. The main goal of the Pepper Scholars
Program is to positively affect collaborative behaviors and investigator productivity through
interactive sessions and other mechanisms of interaction and support. This program was
developed during fall 2009 by Drs. Bandeen-Roche, Gerstenblith and Walston, and the center
administrator, Brian Buta; the first session was held in February 2010, and sessions have
continued monthly since that time. More information is available on our website, including a full
list of presentations: http://www.jhsph.edu/agingandhealth/oaic/Pepper%20Scholars%20Program.
Specific Aim 7:
We have organized strong participation from our OAIC in the National Pepper Centers Annual
Meeting held in April 2011. Our PI, and co-PI, along with our Biostatistics Core Director, Dr. Xue,
attended, along with supported investigators Drs. Boyd (former RCDC) Carlson (former RCDC),
Chaves (CTU), Dobrosielski (RCDC), Kalyani (Pilot), Lin (RCDC), Pustavoitau (RCDC), Talegawkar
(Small Pilot), and J. Wang (Genetics Core Development). Dr. Bandeen-Roche and Dr. Walston
participated as Senior Faculty personnel. Dr. Cynthia Boyd led the Junior Faculty Plenary Session on
“Multi-morbidity assessment in aging research: what to measure and how to measure it.” Drs. Frank
Lin and Jiou Wang presented posters, and Ms. Tyesha Burks, a graduate student who is now a diversity
supplement awardee to our center, working with Pepper Scholar Dr. Ronald Cohn, also presented at
the poster session. Dr. Dobrosielski participated in the mock study section.
II.F Diversity Supplement Award to Ms. Tyesha Burks (3P30AG021334-08S1)
Mentors: Ronald Cohn, MD, Jeremy Walston, MD
Background and Overview:
Ms. Burks’s research and career development plan includes laboratory-based experience and
participation in a range of didactic teaching and review sessions that are an integral part of the
Johns Hopkins OAIC. As a pre-doctoral student developing her thesis in molecular biology, she
has performed preliminary studies on skeletal muscle using two experimental approaches in aging
animals. Given the importance of skeletal muscle decline to the syndrome of frailty, the
experiments as described below are well suited to the Hopkins OAIC. Ms. Burks continues a line
of investigation that was supported in 2009-2010 by a peer-reviewed, competitive OAIC pilot
award given to Dr. Cohn. The basis of this study include the documentation that there is an agerelated increase in TGF-beta signaling and that this increase affects the ability of aged satellite cells
to activate upon injury (Carlson et al., 2008) and the work in other mouse models of myopathic
states that showed Losartan can reduce the amount of TGF-beta signaling and improve skeletal
muscle regeneration (Cohn et al., 2007) Ms. Burks continues this line of investigation as part of her
training and evaluate the effect of a reduction of TGF-beta signaling in muscle regeneration during
aging. These laboratory-based studies are highly relevant to frailty research, and have outstanding
translational potential. As part of the original OAIC pilot award, Ms. Burks conducted experiments
in which aging mice were treated with either placebo, Losartan (an angiotensin II type I receptor
blocking agent), or a TGF-beta neutralizing antibody and then injected with a muscle-damaging
agent, cardiotoxin. Preliminary histological results show a striking difference between treatment
groups with recovery of regenerative capacity of muscle tissue after injury in the Losartan-treated
group. Building on these findings, Ms. Burks has hypothesized that Losartan markedly
improves skeletal muscle healing after injury. She has further hypothesized that Losartan will
slow the development of aging-related muscle decline (sarcopenia). She has proposed to test
these hypotheses using the following specific aims and methodology:
Specific Aim 1: To determine if Losartan improves the rate of recovery of injured skeletal muscle
in 21 month old C57Bl6 male mice by comparing muscle morphometry, function and protein
expression between animals treated with Losartan and animals receiving placebo.
Preliminary results have shown that Losartan improves the regenerative capacity of aged skeletal
muscle after injury by increasing the number of newly regenerating fibers at 4 days post-injury and
by reducing the formation of connective tissue by 18 days post-injury. Ms. Burks, Dr. Cohn and
colleagues are interested in investigating if Losartan improves the in vivo function of the muscles at
18 days post-injury after complete regeneration is thought to have occurred. In order to complete
this aim, they obtained 21-month-old C57Bl6 male mice from the NIA repository. The mice were
treated with Losartan or placebo ad libitum for 1 week prior to the cardiotoxin injection into the
tibialis anterior and the treatment continues throughout the duration of the healing process. At the
18 day time-point, the mice were subjected to the in vivo muscle function testing and then sacrificed
using an inhalation overdose of halothane. The skeletal muscles were flash-frozen for biochemical
analyses and embedded for histological analyses. Biochemical analyses were performed using
Western blots of the muscle synthesis/breakdown (AKT-FOXO3a), endurance (PGC-1alphaAMPK), and the resistance (mTor) pathways. Histological analyses included measurement of fiber
size and variation of fiber size as determined by the minimum Feret’s diameter (Cohn et al., 2007).
Furthermore, the investigators performed dedicated analyses of fiber types in these muscles.
Specific Aim 1 has been successfully completed. The histological results obtained in the tibialis
anterior (TA) are similar to the results obtained previously in the gastrocenemius. Additionally,
Losartan improved the function of the regenerated TA muscle as compared to the placebo. The
western blot analyses showed that Losartan modulated both the canonical and non-canonical TGF-beta
pathways and the muscle regulatory factors at 19d post-injection. However, the effects seen at 4d postinjury were treatment-independent. These results will be published in Science Translational Medicine
on May 11, 2011.
Burks TN, Andres-Mateo, E. Marx R, Mejias R. Van Erp C, Simmers JL, Walston JD, Ward CW,
Cohn RD. Losartan restores skeletal muscle remodeling and protects against disuse atrophy in
sarcopenia. Sci Transl Med. 2011 May 11;3(82):82ra37. PMID:21562229
Specific Aim 2: To determine if 3-6 months of Losartan treatment compared to placebo improves
in vivo limb skeletal muscle strength and modify fiber size and number in aging animals.
Given the effects of Losartan on improving muscle regeneration after injury in sarcopenic mice, the
investigators are interested in evaluating the effect of Losartan on the progression of sarcopenia.
Therefore, they obtained 15-month old mice from the NIA repository and treated them with
Losartan ad libitum for a total of 6 months. The mice were subjected to muscle contractile assays at
3- and 6-months of treatment to determine muscle strength and fatigability. The muscle contractile
assay is an in vivo assessment of the tibialis anterior (TA) muscle (Ashton-Miller et al., 1992); the
mice were anesthetized with Avertin and electrical pulses stimulated the TA muscle via electrodes.
This produces a measurement of the isometric tension and rate of fatigue. This protocol is similar
to the in vitro measurements of muscle function (Shtifman et al., 2008). At the completion of the 6
months of treatment and the final muscle function testing, the mice were sacrificed using an
inhalation overdose of halothane and the skeletal muscle flash frozen and embedded. The samples
were subjected to biochemical analyses of the muscle synthesis/breakdown pathway (AKTFOXO3a), endurance (PGC-1alpha-AMPK), and the resistance (mTor) pathways via Western Blots.
And as mentioned above, morphometric analyses were used to determine muscle fiber size,
homogeneity and fiber type.
At present, the preliminary results have been inconsistent. Therefore, Ms. Burks, Dr. Cohn and
colleagues are currently repeating the experiment to increase the n number and determine the effect
of Losartan on sarcopenia.
Career Development Experiences and Mentorship in Aging Research Proposed for Tyesha Burks:
As stated in the application abstract, each OAIC supported investigator received individualized
attention in order to develop well-suited mentorial panels and access to appropriate research programs
and technology that will facilitate aging and frailty-related research. Ms. Burks is embedded within a
rich milieu of clinical and basic scientists who work within the OAIC who help her gain broad
exposure to academic role models who teach her about hypothesis development, study design,
molecular technology, database development, and data analysis. She also has access to a series of
didactic lectures, seminars, and research focused meetings where she gains broad exposure to aging
research that spans from molecular biological to clinical translational. These experiences directly
relate to the research goals and objectives of the parent grant and of the OAIC pilot grant awarded to
Dr. Cohn in 2009. The pilot grant outlined experiments to characterize and evaluate the time course of
alterations in the TGF-beta signaling pathway in aging mice and its impact on skeletal muscle
regeneration in response to injury. Her study is a natural next step in that it builds on previous findings
and experiences from the pilot award. The elucidation of such pathways and the potential application
of this knowledge to interventions that impact frailty are closely aligned with the stated aims of the
parent grant. The project has potential translational implications, which is an integral part of the goal
of fits our OAIC. Ms. Burks’s specific aims fit well within the scope of the Johns Hopkins OAIC as
described in the abstract. Her project benefits directly from the resources of RC-1 and RC-2, and from
the ongoing mentorial relationships that Ms. Burks will have with her primary mentor Dr. Ronald
Cohn and within the OAIC.
Mentorship Team: Dr. Cohn will continue to provide her with primary scientific mentorship related to
the TGF-beta signaling pathway and to pathophysiology of late-life or disease-induced muscle decline
through regular laboratory and mentorship meetings as part of his OAIC and larger laboratory grant
portfolio. He will provide mentorship, oversight on experimental design, basic biology technology
utilization, abstract and manuscript writing. Dr. Cohn and Ms. Burks meet at least 2-3 times per week,
often interacting on a daily basis.
Ms. Burks has also meets monthly with Dr. Walston to review progress and to receive help with
hypothesis and study design issues.
Career Development Experiences: As part of her OAIC mentorship plan, she is integrated into all of
the relevant training experiences of the OAIC. This includes monthly trainee-focused frailty
research conferences. This forum, attended by students, fellows, and senior and junior faculty, is
integral in helping OAIC supported investigators receive critical feedback and collaborative
interactions that help research programs to flourish. In addition, a regular journal club is organized
as part of this initiative where aging, frailty, and Geriatrics-focused literature is reviewed and
potential translational and implications to clinical practice are discussed. Ms. Burks is expected to
present her results at national meetings of the Gerontological Society of America, and at the
Division of Gerontology and Geriatric Medicine at Johns Hopkins University during the research in
progress section of grand rounds. She presented a very well received poster at the OAIC annual
meeting in April, 2010 for her primary mentor Dr. Cohn, and again presented at the 2011 OAIC
annual meeting in April of this year. These presentation opportunities provided her further exposure
to clinically relevant aging research, and help enabled contacts which can lead to translational
projects in the future. This is in addition to her ongoing full participation in the Cohn lab meetings,
which offer the opportunity to practice research presentations, receive constructive criticism, and
develop next generation hypotheses. They also allow for the opportunity to listen to other lab
members’ presentations and offer critiques and new approaches. In addition, she has the opportunity
to work closely with multiple investigators who have great expertise in the analysis of gene expression
data and in biological data related to frailty, and have broad exposure to the network of expertise
available to trainees sponsored by the other OAIC’s in the US.
Classroom Learning: In order to round out her skill set in basic biology, Ms, Burks completed two
graduate courses related to aging. The first was the Biological Basis of Aging, a graduate level course
taught annually at the Johns Hopkins School of Public Health. This course provided important insights
into critical signal transduction pathways and systems that are altered with aging, as well as knowledge
to connect her research into the larger field of biological aging. She has also taken a course called
‘Health Issues for Aging Populations’ in order to gain important insights into how aging impacts
human health, and how her own research may potentially be translated in order to improve the health
and well being of older adults.
Didactic Learning: Ms. Burks also has numerous opportunities to learn more about molecular research
and aging research through a number of journal clubs and lecture series, such as the COAH Seminars
on Aging Series, Johns Hopkins Division of Geriatric Medicine and Gerontology Grand Rounds and
Biology of Frailty meetings, The McKusick-Nathans Institute on Genetic Medicine (IGM) Journal
Club and Seminars, Epidemiology and Biostatistics of Aging Research-in-Progress Meetings, and the
Pepper Scholars Program.
III.
CAREER DEVELOPMENT (new subsequent to Pepper Funding)
Subsequent funding by supported investigators:
Abadir, Peter (RCDC/Small Pilot)
• Peter Abadir. K-23 award: Age Related Changes in Angiotensin Receptors and its Contribution
to Chronic Inflammation. Funded 1/1/2011.
Arking, Dan (Pilot)
• Dan Arking. Association of KLOTHO with sub-clinical measures of cardiovascular disease in
MESA. American Heart Association. Funded 7/1/2007-6/30/2009.
• Dan Arking. Integrative Genetic Analysis of Autism Brains. Simons Foundation Autism
Research Initiative. Funded 07/15/09-06/30/2012.
Boyd, Cynthia (RCDC)
• Cynthia Boyd (Principal Investigator). Pfizer/AGS Foundation for Health in Aging Junior
Faculty Scholars Program for Research on Health Outcomes in Geriatrics. 07/01/2002 to
12/31/04.
• Cynthia Boyd. Treatment Burden in Older Adults with Diabetes and Multimorbidity.
NIA/AFAR/ Beeson. Funded.
Carlson, Michelle (RCDC)
• Michelle C. Carlson, PhD (Principal Investigator). Cognitive pathways to disability. National
Institute on Aging. Period: 9/30/2002-9/1/2007.
• Michelle C. Carlson, PhD (Principal Investigator). Diversity supplement to Cognitive
pathways to disability. National Institute on Aging. Period: 3/1/06-9/1/2007.
• Michelle C. Carlson, PhD. Bechtel Foundation Gift: Toward a Cognitive Frailty Screen
• Period: 12/31/2004-12/31/2007.
Chaves, Paulo (RCDC/CTU)
• Paulo Chaves. Pathogenesis of Disability in Aging Women (R37). Funded 9/1/20088/31/2011.
• Paulo Chaves. Cardiovascular Health Study: Events. NHLBI (Subcontract to Dr. Bruce Psaty,
University of Washington). Funded 12/16-06 – 5/31/14.
• Paulo Chaves. Anemia of Chronic Kidney Disease and Inflammation in Older Adults. Funded
7/1/2007-6/30/2009.
Leng, Sean (RCDC/Pilot)
• Sean X. Leng. Paul Beeson Career Development Award in Aging Research (K23 AG028963):
Vaccine-Induced Immunity against Influenza in frailty. National Institute on Aging (NIA) /
American Federation for Aging Research (AFAR) and private foundations. 9/1/20068/31/2011.
• Sean X. Leng. The Peking Union Medical College Hospital Geriatric Medicine Program.
China Medical Board of New York. Funded 7/1/2006-6/30/2010.
• Sean X. Leng (Principal Investigator). R21 AG024235: Inflammation-Gene Expression by
Monocytes in Frailty. NIH/NIA. 9/1/2004-6/30/2006.
Lin, Frank R. (RCDC)
• Frank Lin. K-23 award: Impact of Hearing Loss on Health and Functioning in Older Adults.
Funded 12/1/2010.
Makary, Martin (RCDC)
• Martin Makary. Dennis W. Jahnigen Career Development Scholars Award. 2005.
Mielke, Michelle (Pilot)
•
•
Michelle Mielke. Blood-based lipid biomarkers reflective of Alzheimer-associated
neurodegeneration (R21). Funded 7/15/2007.
Michelle Mielke. Development of blood lipid biomarkers for Alzheimer’s disease progression.
Funded 9/1/2007.
Neptune, Enid (Pilot)
• Enid Neptune. The role of Hepatocyte Growth Factor Signaling in Airspace Homeostasis.
Funded 8/1/2007-7/31/2012.
• Enid Neptune. Tissue-based validation of COPD Genetic Studies using Ling Health Study
Cohort (R03). Funded 9/30/2008-9/29/2010.
Polotsky, Vsevolod
• Vsevolod. Polotsky Sleep Apnea and Dysregulation of Lipid Metabolism (R01). NIH. Funded
4/1/10 – 3/30/15.
Roy, Cindy (RCDC)
• Cindy Roy. Mechanisms of anemia of chronic inflammation, aging and frailty in mice. NIH.
Funded. 9/15/2009- 8/31/2014.
Semba, Richard (Pilot)
• Richard Semba. Oxidative stress and pathogenesis of sarcopenia and disability in older
women. NIA . Funded 9/1/2005-8/31/2009.
Seplaki, Christopher (RCDC)
• Christopher Seplaki. Aging-related biodemography of life course physiology and
environmental modifiers (K01). Funded 4/1/2009.
Varadhan, Ravi (Pilot/RCDC)
• Ravi Varadhan (PI). Methods to Study the Heterogeneity of Treatment Effects in Comparative
Effectiveness Research. AHRQ. Funded 9/30/2009 to 01/29/2011.
• Ravi Varadhan. 2011 Brookdale Leadership in Aging Fellowship Award: research to better
delineate the applicability of intervention trial findings to populations not well-represented in
trials, such as older adults. Funded 3/1/2011.
Walston, Jeremy (Pilot/Genetics)
• Jeremy Walston. NFkB related genetic influences on inflammation and poor health in older
adults (R01). Funded 9/1/2006-8/31/2010.
• Jeremy Walston. NIA Long Life Family Study (LLFS). Subcontract to University of
Pittsburgh U01AG023744. Funded 5/1/05 – 5/31/10
• Jeremy Walston. Development of a Mouse Model for Frailty (R21). Funded 9/1/20075/31/2010.
• Jeremy Walston and Laura Dugan. Hartford/AFAR Collaborative Beeson Research Award:
Systemic Inflammation and Central Nervous System Dysfunction: A Mechanistic and
Translational Pilot. Funded 8/1/2007-7/31/2009.
Wang, George (RCDC)
• George Wang. Immunologic Dysregulations and Inflammation in the Pathogenesis of Frailty
of Old Age: The Role of CMV Infection. T. Franklin Williams. Funded 7/1/2008-6/30/2010.
•
George Wang. NIH K23: CMV-specific memory CD8+T cells and TCR diversity and frailty.
Funded 10/1/2010.
Yuh, David (RCDC)
• David Yuh. National Institutes on Aging R21 (Submitted 2/2007): Role of Inflammatory StressResponse and Complications among Older Patients Undergoing Coronary Artery Bypass Surgery.
IV.
PUBLICATIONS (directly resulting from Pepper Resources)
2010:
Crentsil V. Mechanistic contribution of carnitine deficiency to geriatric frailty. Ageing Res Rev. 2010
Jul;9(3):265-8. Epub 2010 Mar 17. PMID: 20223299.
Crentsil V, Ricks MO, Xue QL, Fried LP. A pharmacoepidemiologic study of community-dwelling,
disabled older women: Factors associated with medication use. Am J Geriatr Pharmacother. 2010
Jun;8(3):215-24. PMID: 20624611.
Franckowiak SC, Dobrosielski DA, Reilley SM, Walston JD, Andersen RE. Maximal Heart Rate
Prediction in Adults that are Overweight or Obese. J Strength Cond Res. 2010 Nov 24. [Epub ahead of
print]. PMID: 21116203.
Makary MA, Segev DL, Fried LP, Syin D, Bandeen-Roche K, Patel P, Devgan L, Holzmueller CG,
Tian J, Pronovost PR. Frailty as a Predictor of Surgical Outcome in Older Patients. J Am Coll Surg.
2010 Jun;210(6):901-8. Epub 2010 Apr 28. PMID: 20510798.
Matteini AM, Walston JD, Bandeen-Roche K, Arking DE, Allen RH, Fried LP, Chakravarti A, Stabler
SP, Fallin MD. Transcobalamin-II variants, decreased vitamin B12 availability and increased risk of
frailty. J Nutr Health Aging. 2010 Jan;14(1):73-7. PMID: 20082058.
Matteini AM, Fallin MD, Kammerer CM, Schupf N, Yashin AI, Christensen K, Arbeev KG, Barr G,
Mayeux R, Newman AB, Walston JD. Heritability Estimates of Endophenotypes of Long and Health
Life: The Long Life Family Study. J Gerontol A Biol Sci Med Sci. 2010 Sep 2. [Epub ahead of print].
PMID: 20813793
Moore AZ, Biggs ML, Matteini AM, O’Connor A, McGuire S, Beamer B, Fallin MD, Fried LP,
Walston J, Chakravarti A, Arking DE. Polymorphisms in the mitochondrial DNA control region and
frailty in older adults. PLoS One. 2010 Jun 10;5(6):e11069. PMID: 20548781. PMCID:
PMC2883558.
Rosenberg PB, Mielke MM, Xue QL, Carlson MC. Depressive symptoms predict incident cognitive
impairment in cognitive healthy older women. Am J Geriatr Psychiatry. 2010 Mar;18(3):204-11.
PMID: 20224517.
Roy CN. Anemia of inflammation. Hematology Am Soc Hematol Educ Program. 2010;2010:276-80.
PMID:21239806.
Semba RD, Patel KV, Ferrucci L, Sun K, Roy CN, Guralnik JM, Fried LP. Serum antioxidants and
inflammation predict red cell distribution width in older women: The Women's Health and Aging
Study I. Clin Nutr. 2010 Oct;29(5):600-4. 2010 Mar 22. [Epub ahead of print] PMID: 20334961
Sourial N, Wolfson C, Bergman H, Zhu B, Karunananthan S, Quail J, Fletcher J, Weiss D, BandeenRoche K, Béland F. A correspondence analysis revealed frailty deficits aggregate and are
multidimensional. J Clin Epidemiol. 2010 Jun;63(6):638-46. Epub 2009 Nov 6.
Sourial N, Wolfson C, Zhu B, Quail J, Fletcher J, Karunananthan S, Bandeen-Roche K, Béland F,
Bergman H. Correspondence analysis is a useful tool to uncover the relationships among categorical
variables. J Clin Epidemiol. 2010 Jun;63(6):647-54. Epub 2009 Oct 31.
Tanaka T, Roy CN, Yao W, Matteini A, Semba RD, Arking D, Walston JD, Fried LP, Singleton A,
Guralnik J, Abecasis GR, Bandinelli S, Longo DL, and Ferrucci L. A Genome-Wide Association
Analysis of Serum Iron Concentrations. Blood 2010; 115(1):94-96. PMID: 19880490
Varadhan R, Weiss CO, Segal JB, Wu AW, Scharfstein D, Boyd C. Evaluating health outcomes in the
presence of competing risks: a review of statistical methods and clinical applications. Med Care. 2010
Jun;48(6 Suppl):S96-105. PMID: 20473207
Wang GC, Talor MV, Rose NR, Cappola AR, Chiou RB, Weiss C, Walston JD, Fried LP, Caturegli P.
Thyroid autoantibodies are associated with a reduced prevalence of frailty in community-dwelling
older women. J Clin Endocrinol Metab. 2010 Mar;95(3):1161-8. Epub 2010 Jan 8. PMID: 20061418.
Wang GC, Kao WH, Murakami P, Xue QL, Chiou RB, Detrick B, McDyer JF, Semba RD, Casolaro
V, Walston JD, Fried LP. Cytomegalovirus Infection and the Risk of Mortality and Frailty in Older
Women: A Prospective Observational Cohort Study. Am J Epidemiol. 2010 May 15;171(10):1144-52.
Epub 2010 Apr 16. PMID: 20400465.
Weiss CO, Hoenig HH, Varadhan R, Simonsick EM, Fried LP. Relationships of cardiac, pulmonary,
and muscle reserves and frailty to exercise capacity in older women. J Gerontol A Biol Sci Med Sci.
2010 Mar;65(3):287-94. Epub 2009 Oct 12. PMID: 19822621.
Xue QL, Beamer BA, Chaves PH, Guralnik JM, Fried LP. Heterogeneity in rate of decline in grip,
hip, and knee strength and the risk of all-cause mortality: the Women's Health and Aging Study II.J
Am Geriatr Soc. 2010 Nov;58(11):2076-84. PMID:21054287
2011:
Abadir PM. The frail renin-angiotensin system. Clin Geriatr Med. 2011 Feb;27(1):53-65.
PMID:21093722.
Abadir PM, Walston JD, Carey RM, Siragy HM. Angiotensin II Type-2 Receptors Modulate
Inflammation Through Signal Transducer and Activator of Transcription Proteins 3 Phosphorylation
and TNFα Production. J Interferon Cytokine Res. 2011 Jun;31(6):471-4. Epub 2011 Feb 2.
PMID:21288138
Burks TN, Andres-Mateo, E. Marx R, Mejias R. Van Erp C, Simmers JL, Walston JD, Ward CW,
Cohn RD. Losartan restores skeletal muscle remodeling and protects against disuse atrophy in
sarcopenia. Sci Transl Med. 2011 May 11;3(82):82ra37. PMID:21562229
Burks TN and Cohn RD. Role of TGF-β signaling in inherited and acquired myopathies. Skeletal
Muscle. In Press.
Ho YY, Matteini AM, Beamer BA, Fried LP, Xue Q-L, Arking DE, Chakravarti A, Walston JD, Fallin
D. Exploring Biologically Relevant Pathways in Frailty. J Gerontol A Biol Sci Med Sci. 2011; in press.
Kalyani RR, Metter EJ, Ramachandran R, Chia CW, Saudek CD, Ferrucci L. Glucose and Insulin
Measurements From the Oral Glucose Tolerance Test and Relationship to Muscle Mass. J Gerontol A
Biol Sci Med Sci. 2011 Feb 24. [Epub ahead of print] PMID:21350243.
Ko F, Yu Q, Xue QL, Yao W, Brayton C, Yang H, Fedarko N, Walston J. Inflammation and mortality
in a frail mouse model. Age (Dordr). 2011 Jun 2. [Epub ahead of print] PMID: 21633802.
Leng SX, Qu T, Semba RD, Li H, Yao X, Nilles T, Yang X, Manwani B, Walston JD, Ferrucci L,
Fried LP, Margolick JB, Bream JH. Relationship between cytomegalovirus (CMV) IgG serology,
detectable CMV DNA in peripheral monocytes, and CMV pp65(495-503)-specific CD8 (+) T cells in
older adults. Age (Dordr). 2011 Jan 28. [Epub ahead of print]. PMID: 21274637.
Leng SX, Li HF, Xue Q-L, Yao X, Tian J, Yang X, Ferrucci L, Fedarko N, Fried LP, Semba RD.
Association of detectable cytomegalovirus (CMV) DNA in monocytes rather than positive CMV IgG
serology with elevated neopterin levels in community-dwelling older adults. Exp Gerontol. 2011; in
press.
Lin FR, Thorpe R, Gordon-Salant S, Ferrucci L. Hearing Loss Prevalence and Risk Factors Among
Older Adults in the United States. J Gerontol A Biol Sci Med Sci. 2011 Feb 27. [Epub ahead of print].
Moseley KF, Dobrosielski DA, Stewart Kj, Jan De Beur SM, Sellmeyer DE. Lean mass and fat mass
predict bone mineral density in middle-aged individuals with non-insulin -requiring type 2 diabetes
mellitus. Clin Endocrinol (Oxf). 2011 May;74(5):565-71. doi: 10.1111/j.1365-2265.2010.03965.x.
Epub 2010 Dec 24.
Reinke C, Bevans-Fonti S, Grigoryev DN, Drager LF, Myers AC, Wise RA, Schwartz AR, Mitzner W,
Polotsky VY. Chronic intermittent hypoxia induces lung growth in adult mice. Am J Physiol Lung
Cell Mol Physiol. 2011 Feb;300(2):L266-73. Epub 2010 Dec 3. PMID:21131398.
Roy CN. Anemia in frailty. Clin Geriatr Med. 2011 Feb;27(1):67-78. PMID:21093723.
Walston JD. Frailty. Preface. Clin Geriatr Med. 2011 Feb;27(1):xi. No abstract available.
PMID:21093717.
Weiss CO. Frailty and chronic diseases in older adults. Clin Geriatr Med. 2011 Feb;27(1):39-52.
Review. PMID:21093721.
Xue QL. The frailty syndrome: definition and natural history. Clin Geriatr Med. 2011 Feb;27(1):1-15.
Review. PMID:21093718.
Xue Q-L, Walston JD, Fried LP, Beamer BA. Rate of decline in grip strength predicts the risk of
falling, physical disability, and frailty: The Women’s Health and Aging Study. Arch Intern Med. 2011;
in press.
Yao X, Hamilton R, Weng N-P, Xue Q-L, Bream JH, Tian J, Yeh S-H, Resnick B, Xu XY, Walston
JD, Fried LP, Leng SX. Frailty is associated with poor vaccine-induced antibody response and
increased influenza infection in community-dwelling older adults. Vaccine. 2011; in press.
Yao X, Li H, Leng SX. Inflammation and immune system alterations in frailty. Clin Geriatr Med.
2011 Feb;27(1):79-87. PMID: 21093724.
Zhang T, Mullane PC, Periz G, Wang J. TDP-43 neurotoxicity and protein aggregation modulated by
heat shock factor and insulin/IGF-1 signaling. Hum Mol Genet. 2011 Mar 11. [Epub ahead of print]
PMID: 21355045.
The Johns Hopkins University
Claude D. Pepper Older Americans Independence Center
2011 OAIC Annual Directory: Additional Information
1. Recognition and Awards:
•
Peter Abadir, MD, RCDC supported investigator, was selected for the Presidential Poster
Session at the 2010 Annual Scientific Meeting of the American Geriatrics Society. May 2010.
•
Cynthia Boyd, MD, former RCDC supported investigator, was selected as the 2010 recipient of
the AGS Outstanding Scientific Achievement for Clinical Investigation Award. April 2010.
•
Dr. Paulo Chaves, MD, PhD, Clinical Translation Unit Director, was selected for the
Presidential Poster Session at the 2010 American Geriatrics Society Annual Meeting. May
2010.
•
Dr. Frank Lin, MD, PhD, RCDC supported investigator, won the 1st place award at the 4th
Annual Research on Aging Showcase poster competition organized by the Johns Hopkins
Center on Aging and Health and the School of Public Health Gerontology Interest Group, along
with members of the University of Maryland Pepper Center, in April 2011.
•
Dr. Ravi Varadhan, PhD, Biostatistics Core Development Project investigator, received a
Brookdale Leadership in Aging Fellowship Award in March 2011.
•
Dr. Jeremy Walston, MD, Principal Investigator, was installed as the Raymond and Anna
Lublin Professor of Geriatric Medicine in the Johns Hopkins University School of Medicine
Division of Geriatric Medicine and Gerontology, April 2011.
•
Dr. George Wang, MD, PhD, RCDC supported investigator, was selected for the Oral Paper
Presentation at the 2010 American Geriatrics Society Annual Meeting. May 2010.
•
Dr. George Wang, MD, PhD, RCDC supported investigator, was also selected for the Oral
Paper Presentation at the 2011 American Geriatrics Society Annual Meeting. May 2011.
•
Dr. Qian-Li Xue, PhD, Biostatistics Core Director was named the Nathan Shock Scholar in the
Johns Hopkins Division of Geriatric Medicine and Gerontology. The Nathan Shock Scholar
fund is used to support the research career of a junior faculty member in the division. April
2010.
Pilot Project:
Gene-environment Interactions in Aging, Functional Decline and Disease
Svati Shah, M.D., Project Leader
Funding Years 2007-2009
The overall goal of this work is to study the interactions between aging, genetics and
environment on the risk and development of (or protection from) complex diseases that
commonly cause disability and loss of independence in older adults. The study of risk factors
and heritability of key diseases in older adults directly relates and leads to functional decline.
Furthermore, multiple disease pathologies and risk factors likely interact to produce disability
and functional decline in older adults. Moreover, these interactions are not localized to old age
alone, but occur throughout the life span, making the study of complex diseases in younger
individuals (e.g., mid-life) as important as older individuals for advancing the understanding of
how these diseases produce functional decline in late life.
For this pilot study, we will study metabolic risk factors for the complex diseases of
cardiovascular disease (CVD) and osteoarthritis (OA). We have chosen to study CVD and OA
risk for several reasons. First, CVD and OA are the two of the most common disabling
conditions affecting older adults in the US. Second, aging is identified as a major risk element
contributing to the development of each of these conditions. Third, ascertainment of samples
from a large family structure four generations will provide a unique opportunity to study the
interactive effects of aging, genetics and environment on the development of arguably the two
most influential conditions affecting functional decline in the aging US population.
We have the extraordinary opportunity to address these issues through access to medical
information, biomarker and genetic sampling in a large complex ethnically-diverse (primarily
African and Native American) family. The family under study (Family C) is one of the oldest
existing extended families in the United States and has a prevalence of disease that mirrors the
rates in the general population, making it valuable for generalizing findings to the US population.
This large multi-generational family resource will provide an innovative means to study the
effects of aging, trait heritability, genetic and environmental factors, and interactions among
these elements for common inherited conditions. There are three specific aims related to this
project:
1). Quantitative measurement of CVD and OA disease-related biomarkers in all sampled family
members;
2). Quantitative assessment of the heritability of metabolic risk factors for CVD and OA
biomarkers, and their interaction with aging in this family;
3). Perform a genome-wide linkage analysis in this Family to map metabolic risk factors for
CVD and OA susceptibility genes.
2
Johnston County Osteoarthritis Project
Virginia Kraus, M.D., Ph.D., Investigator.
The Johnston County Osteoarthritis Project is an ongoing, community-based study of the
occurrence of knee and hip OA in African American and Caucasian residents in a rural county in
North Carolina. Details of this study have been reported previously 24. Briefly, this study
involved civilian, non-institutionalized adults aged 45 years and older who resided in six
townships in Johnston County. Participants were recruited by probability sampling, with oversampling of African Americans. A total of 3,187 individuals were recruited between May 1991
and December 1997. All participants completed a baseline clinical evaluation. Among the
3,187 participants with baseline data, 1,329 were not eligible or available for follow-up
assessments. Reasons that participants were not eligible or available included emigration from
study area (N=161), refusal (N=435), inability to participate due to physical or mental conditions
(N=234), death (N=411), and inability to contact or find (N=88). Assessments at follow-up were
completed from 1999-2003.
Dr. Kraus’s research in musculoskeletal disease has identified important racial differences in
several biomarkers and pain responses. These results impact the use and interpretation of
biomarkers for personalized medicine applications. While Caucasians had higher serum
Hyaluronan levels (an indicator of knee synovitis) than African Americans, African-Americans
had higher levels of the systemic inflammatory biomarker high-sensitivity C-reactive protein
(hsCRP) . In individuals with hip and knee OA, African Americans had higher pain scores.
Racial differences in pain and function were related to psychological factors, including arthritis
self-efficacy, affect, and use of emotion-focused coping. These symptom and biomarker data will
be of increasing importance for early identification of individuals at risk for disease onset and
progression in order to initiate treatment at very early times to avoid irreversible stages of
disease and functional impairment.
Minority Supplements:
Demark-Wahnefried, Ph.D., RD. NIH Minority Supplement to "Promoting Health in Prostate &
Breast Cancer Survivors 3 R01 CA81191-03S1 Project Period: 03/01/2001 - 12/31/2005
Total award: $212,520
Minority Trainee(s):
Kimberly Johnson, M.D., (mentor in survey research, Elizabeth Clipp, Ph.D., RN), Pepper Center
Minority Supplement. End of Life Experiences among African-American Patients. 2002.
Racial Differences in Self-Reported Exposure to Information about Hospice Care
Over the last decade, there has been considerable growth in the use of hospice due in part to
educational campaigns informing the public about the availability of hospice services. However,
the extent to which this information has reached older African Americans, a group historically
underrepresented in hospice, has not been described. We surveyed 200 community-dwelling
older adults (> age 65) regarding prior exposure to information about hospice care. Compared to
Whites (n = 95), African Americans (n = 105) reported significantly less exposure to information
3
about hospice (p = 0.0004). Only 4% of Whites had never heard of hospice whereas nearly onefifth of African Americans (19%) reported that they had never heard of hospice; 71.6% of
Whites and 47.6% of African Americans had heard a lot about hospice. In multivariate analysis
controlling for demographics and health status, African Americans had a two times higher odds
of reporting that they had never heard of hospice or heard only a little about hospice versus heard
a lot about hospice (OR= 2.24 [1.17, 4.27]. Greater exposure to hospice information was
associated with more favorable beliefs about hospice care among older adults in both racial
groups, including beliefs about the kind of treatment that hospice provides and the desire to use
hospice care in the future. Because knowledge is power, efforts to reduce disparities in hospice
use and improve the quality of end-of-life care should include formal educational programs to
dispel myths about hospice and to provide older African Americans with the tools to make
informed choices about end-of-life care.
Dr. Johnson is recipient of a Beeson Career Development Award for this work. (2007-2012)
Publications Pertaining to Minority Research:
1992
1. Anderson, N. B., McNeilly, M., & Myers, H. (1992). Toward Understanding Race
Differences in Reactivity: A Proposed Contextual Model. In R. Turner, A. Sherwood, &
K. C. Light (Eds.), Individual Differences in Cardiovascular Responses to Stress (pp. 12140): Plenum.
1993
2. Anderson, N. B., & McNeilly, M. (1993). Autonomic Reactivity and Hypertension in
Blacks: Toward a Contextual Model. In J. S. Fray & J. Douglas (Eds.), The
Pathophysiology of Hypertension in Blacks (pp. 107-139): Oxford University Press.
3. Anderson, N. B., McNeilly, M., & Myers, H. (1993). A Biopsychosocial Model of Race
Differences in Vascular Reactivity. In J. Blascovich & E. S. Katkin (Eds.),
Cardiovascular Reactivity to Psychological Stress and Disease (pp. 83-108): American
Psychological Association.
4. Svetkey, L. P., George, L. K., Burchett, B. M., Morgan, P. A., & Blazer, D. G. (1993).
Black/white differences in hypertension in the elderly: an epidemiologic analysis in
central North Carolina. American Journal of Epidemiology, 137(1), 64-73.
1994
5. Bohannon, A. D., Huber, M., & Fillenbaum, G. G. (1994). Racial Differences in
Psychiatric Symptoms Among Severely Cognitively Impaired Elders. The Gerontologist,
34(Special Issue 1), 92.
6. Burke, J. R., Lewis, K. E., Roses, A. D., Ikeuchi, T., Koide, R., Tsuji, S., Yamada, M.,
Pericak-Vance, M. A., & Vance, J. M. (1994). Dentatorubral-palliodoluysian (DRPLA)
and Haw River Syndrome: Evidence for Differences in Population Frequencies of
Intermediate Alleles Explaining Racial Variation in Prevalence of Disease. Lancet, 344,
1711-1712.
4
7. Burke, J. R., Pericak-Vance, M. A., & Vance, J. M. (1994). Haw River Syndrome (HRS)
and Dentatorubropallidoluysian Atrophy (DRPLA): Disorders with an Identical
Trinucleotide Repeat Expansion but Differences in Clinical Expression with Racial
Frequency. Paper presented at the American Society of Human Genetics, Montreal,
Canada.
8. Clark, R., Anderson, N. B., George, L. K., McNeilly, M. D., Broadhead, E., Tse, C. J.,
Blazer, D. G., & Cornoni-Huntley, J. (1994). Socioeconomic Status and Hypertension in
Black and White Elderly. Paper presented at the Presented at the Forty-Seventh National
Conference of the Gerontological Society of, America Atlanta GA.
9. Galanos, A., Strauss, R., & Pieper, C. (1994). Sociodemographic Correlates of Health
Beliefs Among Black and White Community Dwelling Elderly. The International
Journal of Aging and Human Development, 38(4), 277-288.
10. Schmader, K. E., George, L. K., & Hamilton, J. D. (1994). Racial Differences in the
Occurrence of Herpes Zoster. Paper presented at the Journal of the American Geriatrics
Society.
11. Taussig, I. M., Huber, M., & Fillenbaum, G. G. (1994). The Boston Naming Test-Short
Version. Race and Language Performance. The Gerontologist, 34(Special Issue 1), 248.
12. Welsh, K. A., Wilkinson, W., Fillenbaum, G., Harrell, L., Beekly, D., Edland, S., Stern,
Y., & Mohs, R. (1994). Racial Differences in Neuropsychological Performance in
Alzheimer's Disease. Annals of Neurology, 36, 270.
1995
13. Armstead, C. A., Anderson, N. B., & Siegler, I. C. (1995). The Biopsychosocial
Concomitants of Self-reported Hypertension Among Black and White University Alumni.
Paper presented at the Poster presented at the 10th International Conference on
Hypertension in Blacks, Thomas, US Virgin Islands.
14. Bennett, C. L., Horner, R. D., Weinstein, R. A., Dickinson, G. M., DeHovitz, J. A., Cohn,
S. E., Kessler, H. A., Jacobson, J., Goetz, M. B., Simbercoff, M. S., Pitrak, D. L., George,
W. L., Gilman, S. C., & Shapiro, M. F. (1995). Racial Differences in Care Among
Hospitalized Patients with Pneumocystis Carinii Pneumonia in Chicago, New York, Los
Angeles, Miami, and Raleigh-Durham. Archives of Internal Medicine, 155(15), 15861592.
15. Blazer, D. G., Hays, J. C., & Foley, D. (1995). Sleep Complaints in Older Adults: A
Racial Comparison. Journals of Gerontology: Medical Science, 50A, M280-M284.
16. Fillenbaum, G. G., Horner, R. D., Hanlon, J. T., Landerman, L. R., Dawson, D. V., &
Cohen, H. J. (1995). Change in Use of Prescription (Rx) and Nonprescription (nonRx)
Drugs by Black and White Elderly Living at Home. The Gerontologist, 35, 257.
17. Hays, J. C., Fillenbaum, G. G., Gold, D. T., Shanley, M. C., & Blazer, D. G. (1995).
Black-White and Urban-Rural Differences in Stability of Household Composition
Among Elderly Persons. Journal of Gerontology: Social Sciences, 50B, S301-S311.
5
18. Horner, R. D., Kolasa, K. M., & Irons, T. (1995). Racial Differences in Rural Adults'
Attitudes on Adolescent Health and Sexuality Following a 3-year Adolescent Health
Promotion Campaign. Health Values, 19(3), 5-11.
19. Horner, R. D., Oddone, E. Z., & Matchar, D. B. (1995). Theories Explaining Racial
Differences in the Utilization of Diagnostic and Therapeutic Procedures for
Cerebrovascular Disease. Milbank Quarterly, 73(3), 443-462.
20. Mendes de Leon, C. F., Fillenbaum, G. G., Williams, C. S., Brock, D. W., Beckett, L. A.,
& Berkman, L. F. (1995). Functional Disability in Elderly Blacks and Whites Living in
Two Different Geographic Areas: The New Haven and North Carolina EPESE.
American Journal of Public Health, 85, 994-998.
21. Padgett, D. K., Patrick, C., Burns, B. J., & Schlesinger, H. J. (1995). Use of Mental
Health Services by Black and White Elderly. In D. K. Padgett (Ed.), Handbook of
Ethnicity, Aging, and Mental Health (pp. 145-164). Westport, CT: Greenwood Press.
22. Schmader, K. E., George, L. K., Burchett, B. M., Pieper, C. F., & Hamilton, J. (1995).
Racial Differences in the Occurrence of Herpes Zoster. Journal of Infectious Disease,
171, 701-704.
23. Svetkey, L. P., Timmons, P. Z., George, L. K., Tyroler, H. A., Burchett, B. M., & Blazer,
D. G. (1995). Effects of Sex and Race on Blood Pressure Control in the Elderly.
Presented at the Tenth Scientific Meeting of the American Society of Hypertension May
1995. Am J Hypertension, 8, 40A.
1996
24. Cohen, H. J. (1996). Race and Myeloma Survival (Letter to the Editor). Journal of
Clinical Oncology, 14(12), 3175.
25. Cohen, H. J., Pieper, C. F., Rao, K. M. K., Harris, T., & Currie, M. S. (1996). Disease,
Functional-Status Associations and Racial Differences in Plasma D-dimer Levels in
Community Dwelling Elders. Journal of the American Geriatrics Society, 44, P36.
26. Emovon, O. E., Klotman, P. E., Dunnick, N. R., Kadir, S., & Svetkey, L. P. (1996).
Renovascular Hypertension in Blacks. American Journal of Hypertension, 9, 18-23.
27. Fillenbaum, G. G., Horner, R. D., Hanlon, J. T., Landerman, L. R., Dawson, D. V., &
Cohen, H. J. (1996). Factors Predicting Change in Prescription and Nonprescription Drug
Use in a Community-Residing Black and White Elderly Population. Journal of Clinical
Epidemiology, 49(5), 587-593.
28. Gold, D. T., Pieper, C. F., Westlund, R. E., & Blazer, D. G. (1996). Do Racial
Differences in Hypertension Persist in Successful Agers? Findings from the MacArthur
Study of Successful Aging. Journal of Aging and Health, 8(2), 207-219.
29. Schmader, K. E., George, L. K., Burchett, B. M., Pieper, C. F., & Hamilton, J. D. (1996).
Racial Differences in Herpes Zoster and the Age of Varicell Infection: A Reply. Journal
of Infectious Disease, 174, 239-241.
6
30. Svetkey, L. P., Timmons, P. Z., Emovon, O., Dawson, D. V., Lefkowitz, R. J., Anderson,
N. B., & Chen, Y.-T. (1996). Association Between Essential Hypertension in Blacks and
Beta2-Adrenergic Receptor Genotype. Presented at the Council for High Blood Pressure
Research, September 1995. Circulation, 94, I33.
1997
31. Horner, R., Hoenig, H., Sloane, R., Rubenstein, L. V., & Kahn, K. (1997). Racial
Differences in Utilization of Inpatient Rehabilitation Services Among Elderly Stroke
Patients. Stroke, 28(1), 19-25.
32. Mendes de Leon, C. F., Beckett, L. A., Fillenbaum, G. G., Brock, D. B., Branch, L. G.,
Evans, D. A., & Berkman, L. F. (1997). Black-White Differences in Risk of Becoming
Disabled and Recovering from Disability in Old Age: a longitudinal analysis of two
EPESE populations. American Journal of Epidemiology, 145(6), 488-497.
33. Svetkey, L. P., Chen, Y.-T., McKeown, S. P., Preis, L., & Wilson, A. F. (1997).
Preliminary evidence of linkage of salt sensitivity in black Americans at the beta 2adrenergic receptor locus. Hypertension, 29(4), 918-922.
1998
34. Cohen, H. J., Crawford, J., Rao, M. K., Pieper, C. F., & Currie, M. S. (1998). Racial
Differences in the Prevalence of Monoclonal Gammopathy in a Community-Based
Sample of the Elderly. American Journal of Medicine, 104, 439-444.
35. Demark-Wahnefried, W., Schildkraut, J. M., Iselin, C. E., Conlisk, E., Kavee, A.,
Aldrich, T. E., Lengerich, E. J., Walther, P. J., & Paulson, D. F. (1998). Treatment
options, selection and satisfaction among black and white men with prostate cancer in
North Carolina. Cancer, 83, 320-330.
36. Fillenbaum, G. G., Heyman, A., Huber, M. S., Woodbury, M. A., Leiss, J., Schmader, K.
E., Bohannon, A., & Trapp-Moen, B. (1998). Prevalence and three-year incidence of
dementia in older Black and White community residents. Neurology, 50(Supplement 4),
A55.
37. Fillenbaum, G. G., Heyman, A., Huber, M. S., Woodbury, M. A., Leiss, J., Schmader, K.
E., Bohannon, A., & Trapp-Moen, B. (1998). The prevalence and three-year incidence of
dementia in older black and white community residents. Journal of Clinical
Epidemiology, 51, 587-595.
38. Fillenbaum, G. G., Peterson, B., Welsh-Bohmer, K., Kukull, W. A., & Heyman, A.
(1998). Progression of Alzheimer's Disease in Black and White Patients: The CERAD
Experience, Part XVI. Neurology, 51(1), 154-158.
39. Hays, J. C., Galanos, A. N., & Fetzer, D. L. (1998). Epidemiology of Home Deaths in a
Racially Mixed Urban-Rural Community. The Gerontologist, 38, 354.
7
40. Horner, R. D. (1998). Racial Variations in Cancer Care: A Case Study of Prostate
Cancer. In C. Bennett (Ed.), Cancer Policy (2nd Edition ed., pp. 99-114). Norwell, MA:
Kluwer Academic Publishers.
41. Oddone, E. Z., Horner, R. D., Diers, T., Lipscomb, J., McIntyre, L., Sloane, R., Whittle,
J., Passman, L., Patterson, L., Heaney, R., & Matchar, D. (1998). Understanding racial
variation in the utilization of carotid endarterectomy: role of patient preferences. Journal
of National Medical Association, 90(1), 25-33.
42. Schein, R., & Koenig, H. G. (1998). Gender and race effects on the factor structure of
the CES-D in older medical inpatients. Paper presented at the 1998 Gerontological
Society of America 51st Annual Meeting, Washington, DC.
43. Schmader, K. E., George, L. K., Burchett, B. M., & Pieper, C. F. (1998). Racial and
psychosocial risk factors for herpes zoster in the elderly. Journal of Infectious Diseases,
178(Suppl 1), S67-S71.
44. Schmader, K. E., George, L. K., Burchett, B. M., Hamilton, J. D., & Pieper, C. F. (1998).
Race and stress in the incidence of herpes zoster in the elderly. Journal of the American
Geriatrics Society, 46, 973-977.
45. Swartz, M. S., Wagner, H. R., Swanson, J. W., Burns, B. J., George, L. K., & Padgett, D.
K. (1998). Comparing Use of Public and Private Mental Health Services: The Enduring
Barriers of Race and Age. Community Mental Health Journal, 34, 133-143.
1999
46. Blazer, D. G. (1999). Marked racial differences in antidepressant use in an elderly
community study. Paper presented at the Gerontological Society Annual Meeting, San
Francisco.
47. Bohannon, A. D., Hanlon, J. T., Landerman, L. R., Gold, D. T., Langlois, J., & Harris, T.
(1999). Relationship between race and other potential risk factors and nonvertebral
fractures in community-dwelling elderly women. American Journal of Epidemiology,
149, 1002-1009.
48. Bohannon, A. D., Landerman, R., Gold, D., & Hanlon, J. (1999). Association of Race
and Other Potential Risk Factors with Nonvertebral Fractures in Community Dwelling
Elderly Women. Am J Epi, 149, 1002-1009.
49. Campbell, M. K., Demark-Wahnefried, W., Dodds, J., Symons, M., Kalsbeek, W.,
Cowan, A., Motsinger, B., Hoben, K., Lashley, J., Demissie, S., & McClelland, J. (1999).
Improving fruit and vegetable consumption for cancer prevention in communities: the
Black Churches United for Better Health project. Am J Pub Health, 89, 1390-1396.
50. Conlisk, E., Lengerich, E. J., Demark-Wahnefried, W., Schildkraut, J. M., & Aldrich, T.
E. (1999). Prostate cancer: correlates of stage at diagnosis among black and white men in
North Carolina. Abstract # 127. Dallas TX, May 1, 1999. American Urological
Association. Journal of Urology, 161(4S), 36.
8
51. Conlisk, E., Lengerich, E. J., Demark-Wahnefried, W., Schildkraut, J. M., & Aldrich, T.
E. (1999). Prostate cancer: demographic and behavioral correlates of stage at diagnosis
among blacks and whites in North Carolina. Urology, 53(6), 1194-1199.
52. Corti, M. C., Guralnik, J. M., Ferrucci, L., Izmirlian, G., Leveille, S., Pahor, M., Cohen,
H. J., Pieper, C. F., & Havlik, R. (1999). Evidence for a Black-White Crossover in AllCause and Coronary Heart Disease Mortality in an Older Population: The North Carolina
EPESE. American Journal of Public Health, 89(3), 308-314.
53. Fillenbaum, G. G., & Heyman, A. (1999). Diagnostic differences by race: An update
from the CERAD study. A comparison of dementia and AD in Blacks and Whites in
epidemiology studies and in tertiary care. Paper presented at the Presented at 5th Annual
Grayline Conference on Women's Health, Winston-Salem, NC.
54. Oddone, E. Z., Horner, R. D., Sloane, R., McIntyre, L., Ward, A., Whittle, J., Passman,
L. J., Kroupa, L., Heaney, R., Diem, S., & Matchar, D. (1999). Race, presenting signs
and symptoms, use of carotid artery imaging and appropriateness of carotid
endarterectomy. Stroke, 30(7), 1350-1356.
2000
55. Demark-Wahnefried, W., McClelland, J., Jackson, B., Campbell, M. K., Cowan, A.,
Hoben, K., & Rimer, B. K. (2000). Partnering with African American churches to
achieve better health: lessons learned during the Black Churches United for Better Health
5 a Day project. Journal of Cancer Education, 15(3), 164-167.
56. Hegarty, V., Burchett, B. M., Gold, D. T., & Cohen, H. J. (2000). Racial differences in
use of cancer prevention services among older Americans. Journal of the American
Geriatrics Society, 48(7), 735-740.
57. Jones, M. R., Horner, R. D., Edwards, L. J., Hoff, J., Armstrong, S. B., Smith-Hammond,
C. A., Matchar, D. B., & Oddone, E. Z. (2000). Racial variation in initial stroke severity.
Stroke, 31(3), 563-567.
58. Pieper, C., Rao, K., Currie, M., Harris, T., & Cohen, H. (2000). Age, functional status,
and racial differences in plasma d-dimer levels in community-dwelling elderly persons. J
Geront: Med Sci, 55A(11), M649-M657.
59. Wallsten, S. M. (2000). Effects of caregiving, gender, and race on the health, mutuality,
and social supports of older couples. Journal of Aging and Health, 12, 90-111.
60. Whitfield, K. E., Fillenbaum, G. G., Pieper, C., Albert, M. S., Berkman, L. F., Blazer, D.
G., Rowe, J. W., & Seeman, T. (2000). The effect of race and health related factors on
naming and memory: The MacArthur Studies of Successful Aging. Journal of Aging and
Health, 12(1), 69-89.
2001
61. Campbell, MK, Havas, S, Jackson B, Damron, D, McClelland, J, Demark-Wahnfried, W,
Langenberg, P, Cowan , A, Feldman, R, Motsinger, BM. (2001) 5-a-Day research with
9
African American churches and the special supplementation program for women, infants,
and children. NCI Monographs NIH Publication 01-5019-168.
2002
62. Dragomir A, Jordan J, Arab L, Kraus V, Luta G, Stabler T, Renner J, Hochberg M,
Helmick C (2002) Serum cartilage ilogomeric matrix protein (COMP) levels and current
hormone replacement therapy (HRT) in postmenopausal African-American and
Caucasian women. In: Arthritis & Rheumatism. p S373
63. Jordan J, Kraus V, Luta G, Stabler T, Renner J, Dragomir A, Hochberg M, Helmick C
(2002) Serum hyaluronic acid (HA) levels and radiographic knee osteoarthritis (OA) in
African-Americans and Caucasians. In: Arthritis & Rheumtatism. p S464.
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12
Section I. Description of Center
As the home of the first academic department of Geriatrics in the U.S., the Mount Sinai
School of Medicine and the Mount Sinai Medical Center are extremely committed to
Geriatrics and the success of this OAIC. This OAIC responds to the Institute of Medicine
(IOM) report by implementing a rigorous and comprehensive program of research focused on
the increasing numbers of patients and families living with serious and chronic illness.
Specifically, our OAIC builds upon the foundation of pioneering research in aging and
palliative care conducted at Mount Sinai over the past 15 years with the express purpose of
developing and fostering research that, in the words of Claude D. Pepper, will “…lighten the
burden of those who suffer and improve the quality of life and independence for the millions
of older adults living with serious and advanced illness. We intend to accomplish our goal
by addressing the following specific aims:
1. To establish a comprehensive trans-disciplinary research program focused on: a)
exploring the relationship of pain and other distressing symptoms on quality of life,
independence, function, and disability; b) developing interventions directed at the
treatment of pain and other distressing symptoms in older adults; and c) exploring
models of care for older adults living with serious and chronic illness.
2. To identify, recruit, and train leaders in aging and palliative care research through: a)
mentoring relationships with successful investigators; b) strengthening and expanding
Mount Sinai’s existing research training programs in aging and palliative care; and c)
support for pilot projects, statistical and analytic consultation, and instrument
development and measurement.
3. To establish a research infrastructure that will a) support new and ongoing research in
aging and palliative care by providing expertise in research design, measurement, and
analysis, b) develop and apply innovative research designs, analytic techniques, and
measures, and c) apply to aging research, methods not currently in widespread use
(e.g. item response theory, propensity score methods) but which are highly applicable
to geriatrics and gerontology because of the populations studied.
4. To develop a research center that bridges the transdisciplinary specialties of geriatrics
and palliative care that will serve as a model for research that has not been well
addressed by these two specialties.
The overall goal of our center is to bring together a diverse, transdisciplinary group of
distinguished investigators with a strong history of collaboration and research in pain and other
symptoms, functional outcomes, patient-oriented research, research design, biostatistics, and
measurement to establish an OAIC focused on palliative care in older adults.
Section II. Research, Resources and Activities
A. Cores
Our OAIC cores are led by 5 scientists with a strong history of collaboration, expertise in
the OAIC areas of focus, and leadership experience:
Albert Siu, MD (OAIC leader, Leadership and Administrative Core [LAC] leader) The Leadership and Administrative Core (LAC) will be housed in the offices of the
Chairman of the Mount Sinai Department of Geriatrics. Core staff will be the Center PI
and Core Leader (Albert L. Siu, MD), the Leaders of the RCDC (R. Sean Morrison, MD)
PESC (Kenneth Boockvar, MD) RC-RDA (Joan Penrod, PhD, RD-MDM (Jeanne Teresi,
PhD), the Vice-Chair for Education of the Department of Geriatrics (Rosanne Leipzig,
MD, PhD) and the Director of the Center to Advance Palliative Care and the Lilian and
Benjamin Hertzberg Palliative Care Institute (Diane Meier, MD). Three standing
committees advise the Center regarding policy and conduct of its programs: 1) an OAIC
Executive Committee (OAIC EC or EC) of OAIC core leaders and institutional
leadership; 2) a Research Advisory Committee (RAC) of senior investigators not
currently involved in the OAIC as investigators or mentors; and 3) an OAIC External
Advisory Committee (OAIC EAC) of outside experts which meet annually to review
progress.
R. Sean Morrison, MD (Research Career Development Core [RCDC] leader) - The
RCDC addresses the need to train investigators in palliative care and aging research
through Specific Aim 2 of the OAIC: To identify, recruit, and train academic leaders in
geriatrics and palliative care research by: a) establishing formal mentoring relationships
with established and successful senior investigators; b) strengthening and expanding
Mount Sinai’s existing research training programs in geriatrics and palliative care; and c)
by providing core support for pilot projects, design and statistical/ analytic consultation,
and instrument development and measurement. The RCDC contributes to the overall
goals of the OAIC by ensuring the development and sustained availability of welltrained, productive, and established researchers in the field of geriatrics and palliative
care. The RCDC supports recruitment, selection, career development activities,
infrastructure to support training and conduct of research studies, and structured and
consistent advisory and mentoring teams and oversight processes for each investigator.
Tailored to the developmental stage and training needs of each junior faculty member, the
RCDC provides a didactic research training curriculum; biweekly seminars on academic
survival; journal club; monthly research-in-progress seminars for presentation and
discussion of on-going research; individual mentoring; support for measurement and
statistics from the resource cores; and oversight of pilot and exploratory studies within
the OAIC.
Kenneth Boockvar, MD (Pilot and Exploratory Studies Core [PESC] leader) – The
PESC builds upon a 15-year foundation of research in palliative care, disability, and
function at Mount Sinai; an established record of successful mentorship by the OAIC
senior investigators, and a strong and consistent track record in conducting collaborative
and interdisciplinary research that will accomplish the following specific aims:
• Support pilot and exploratory studies that will: a) examine the relationship of pain
and other distressing symptoms to independence, function, and disability; b)
develop interventions directed at the treatment of pain and other distressing
symptoms in older adults; and c) explore interventions to improve quality of life
and promote function and independence for older adults living with serious and
chronic illness.
• Support the development of junior faculty by providing a mechanism to obtain
mentored, hands-on research training and develop preliminary data in aging and
palliative care that will lead to the development of larger federal or foundation
funded research projects and career development awards focused on improving
care and promoting independence for older adults with advanced illness.
• Support senior and mid-level faculty who are conducting: studies in palliative care
and aging and who are embarking on new research projects requiring pilot data;
palliative care research in younger populations and who would like to expand or
shift their research into aging; or aging research unrelated to palliative care who
would like to refocus their work to fit within our OAIC theme.
• Foster collaborative research among investigators from different disciplines,
specialties, and institutions.
Joan Penrod, PhD (Research Core-Research Design and Analysis [RC-RDA]) - The
Research Design and Analysis Core (RC-RDA) contributes to the goals of the OAIC by
providing statistical, methodological and programming expertise, as well as mentoring in
those areas, to investigators in the Mount Sinai OAIC. Expertise is provided in a variety of
ways and throughout all phases of the research process—from design through interpretation
and presentation of findings. The RC-RDA aims are:
o To provide sophisticated, cutting edge methodological, statistical, and recruitment
support to new and existing OAIC investigators by supporting new internal OAIC
(e.g, PESC, RCDC) and external research applications, RCDC and PESC funded
projects, and consultation and services to externally funded research of OAIC
faculty for additional analyses not included in the parent grant.
o To collaborate closely with the Research Career Development Core (RCDC) to
ensure that junior faculty obtain research methods training to advance their
current knowledge and expertise.
o To collaborate with the RC-MDM to obtain data processing and management
appropriate for studies by PESC investigators, junior faculty and other OAIC
investigators.
o To apply sophisticated research and statistical methodology (propensity score
method, instrumental variable estimation, competing risk analysis) used in other
fields but not commonly applied to aging-related research.
o To disseminate this information to other researchers in geriatrics and gerontology
through presentations at scientific meetings and publications in scientific journals.
o To work with and provide consultation to researchers at other OAICs on
methodological challenges of research on older patients with serious and chronic
illness.
Jeanne Teresi, PhD (Research Core –Measurement and Data Management [RCMDM]) – A major barrier to research in this field has been the questionnaire burden on
patients and family members associated with assessing and measuring symptoms,
physical impairment, satisfaction, and caregiver burden. The major goal of the RC-MDM
is to address such measurement challenges using item banking and the methods of
modern psychometric theory through the following specific aims:
o To assist OAIC investigators (from this and other Centers) in evaluating
measures, and, where appropriate, in the selection, use, and construction of item
response theory (IRT) derived measures from existing sources (e.g., the Patient
Reported Outcomes Measurement Information System (PROMIS) Roadmap
Initiative);
o To apply psychometric techniques to items from existing palliative care and
related data sets to test model assumptions, examine distributions and prepare data
for analyses;
o To conduct IRT analyses using data from ongoing NIH funded palliative care
research with the goal of constructing a palliative care item bank as part of a later
developmental project in years 3-5 of this OAIC;
o To provide data management, in coordination with RC-RDA, for studies
supported by the other OAIC cores;
o To disseminate this information to researchers interested in geriatric palliative
care through: a) presentations and publications, b) the National Palliative Care
Research Center (www.npcrc.org) and other major national initiatives; and c)
development of a web site with links to PROMIS and related web sites.
B. Research
1. Palliative Care for Hospitalized Patients with Advanced Cancer (PI: Meier,
NCI/NINR funded). This series of analyses will contribute to the overall OAIC
theme by examining the effect of inpatient palliative care consultation teams
(PCCT) on hospital costs, hospital and intensive care unit lengths of stay, and
readmission rates using sophisticated statistical methods not commonly applied to
aging-related research. The parent study is a multi-site, observational controlled
trial of PCCT compared to usual care for 6900 patients hospitalized with
advanced cancer in five U.S. hospitals. RC-RDA will provide cost and use data
collection, and analyses of cost effects using propensity score matching.
2. Pain and Delirium in an RCT of Perioperative Cognitive Protection (PI:
Silverstein, NIA funded). This series of analyses will contribute to the overall
OAIC theme by examining the relationships among postoperative pain, pain
treatment, delirium and cognitive impairment in older adults using sophisticated
statistical methods. The parent study is an RCT of the effect of perioperative
infusion of dexmedetomidine, an α 2A -adrenergic agonist, compared with standard
care on postoperative delirium and cognitive dysfunction in 706 older adults
undergoing major non-cardiac surgery at 7 U.S. hospitals. We will conduct
analyses not funded by the parent grant first to test the hypothesis that higher pain
scores are associated with an increased incidence of post-operative delirium by
the CAM assessment, using multivariable logistic regression. Second, we will test
the hypotheses that patients receiving patient-controlled analgesia (PCA) will
have lower opioid requirements, reduced pain, and a lower incidence of postoperative delirium, using propensity score methodology to match patients
receiving PCA to those receiving clinician controlled analgesia and using
multivariate logistic regression to examine the association of PCA with postoperative delirium. Third, we will test the hypothesis that opioids with active
metabolites (oxycodone, morphine) are associated with an increased risk of
delirium as compared to opioids without active metabolites (fentanyl,
hydropmorphone), and examine the relationship between opioid dose and
delirium. We hypothesize a U-shaped relationship between opioid dose and
delirium such that low and high doses of opioids will increase the risk of delirium
whereas moderate doses will be protective. We will use propensity score
methodology to match patients receiving each opioid type and multivariable
logistic regression to examine the relationship between drug type and postoperative delirium. To test whether both low and high doses of opioids are
associated with greater delirium, we will include a squared opioid dose term in the
model. The signs on the estimate of the dose and dose squared terms indicate
whether the relationship is U shaped. All models will control for delirium risk
factors, treatment group, opioid dose, and other important covariates. RC-RDA
will provide propensity score methodology, modeling consultation and data
analysis.
3. EP-3: Symptoms and Function during Acute Illness in Nursing Home
Residents (PI: Boockvar; Co-PI Hung, VA funded). This series of analyses
will contribute to the overall OAIC theme by examining the relationships between
pain and other symptoms, medication use, acute illness and function in nursing
home residents using sophisticated statistical methods. The parent study is a
prospective observational cohort of residents of 2 nursing homes in New York
City who have experienced 150 acute illness episodes (e.g., urinary and
respiratory infections). We will conduct analyses not funded by the parent study
to describe the impact on pain, function, and other symptoms of 2 exposures: 1)
periods of acute illness and 2) periods of interruption in opioid analgesics which
are common. Levels of pain, function, and other symptoms during exposure
periods will be compared with pre-exposure periods, controlling for repeated
observations of subjects over time and clustering of subject observations by
provider and nursing home, using GEE. RC-RDA will provide modeling
consultation accounting for clustered observations, and statistical programming
for data analysis.
C. Pilots
Project 1: Cohort Study of Patients with Ventricular Assist Devices to Determine
Symptoms of Patients and their Caregivers
Principal Investigator: Nathan Goldstein, MD Brookdale Department of Geriatrics
and Palliative Medicine, Mount Sinai School of Medicine
Co-Investigators: 1) R. Sean Morrison, MD, Department of Geriatrics and Palliative
Medicine, Mount Sinai School of Medicine 2) Deborah Ascheim, MD, Department of
Health Evidence and Policy, Mount Sinai School of Medicine
Background and Specific Aims: Heart Failure (HF) is a chronic illness typically
associated with multiple co-morbidities, and it is a leading cause of death in the
United States. While medical management is the mainstay therapy for patients with
HF, ventricular assist devices (VADs) are increasingly used to treat HF patients with
end-stage disease. Originally approved as a temporary therapy to “bridge” patients as
they waited for cardiac transplantation, VADs are now implanted in patients whose
eligibility for transplant is unclear (bridge to candidacy) or ineligible for
transplantation (destination therapy). The use of LVADs is expected to increase in the
years to come, especially as devices become smaller and are increasingly associated
with better survival and fewer post-implantation complications (e.g. infection,
bleeding, stroke). While these devices have been shown to improve survival and
quality of life in patients with advanced HF, there are little data exploring the non-HF
physical symptoms (e.g. pain) of patients with these devices or the psychological
symptoms of these patients and their caregivers. This project is a 4-center prospective
cohort study of patients with recently implanted VADs and their caregivers to:
Aim 1: Evaluate baseline prevalence and change over time of physical (pain and
quality of life) and psychological (depression, anxiety, panic disorder) characteristics
and symptoms in patients with VADs.
Aim 2: Evaluate baseline prevalence and change over time of psychological
(depression, anxiety, posttraumatic stress disorder) symptoms in caregivers of
patients with ventricular assist devices.
Aim 2.1: Determine prevalence of prolonged grief disorder among caregivers of
patients with VADs who die.
The project will enroll 100 patients immediately after VAD implantation at Mount
Sinai, Columbia-Presbyterian, University of Pennsylvania, and Jewish Hospital
(Louisville, KY) Medical Centers to determine baseline prevalence of symptoms of
both patients and their caregivers using validated instruments, and then follow them
for up to 12 months to determine how these characteristics change. For those patients
who die during the course of the study, the project will perform after-death interviews
with caregivers. This project will be the first comprehensive exploration dedicated to
determining the non-HF-related physical and psychological symptoms of patients
with VADs and their caregivers. These data will be also be used to support a future
R01 grant application for a randomized controlled trial evaluating whether automatic
palliative care consultation at time of device implant improves outcomes for patients
with VADs and their caregivers.
Project 2: Couple-focused Symptom Management Intervention for Older Lung
Cancer Patients & Their Spousal Caregivers
Principal investigator: Hoda Badr, PhD, Department of Oncological Sciences, Mount
Sinai School of Medicine
Co-Investigators: 1) Juan Wisnivesky, MD; General Internal Medicine, Mount Sinai
School of Medicine; 2) William H. Redd, PhD; Department of Oncological Sciences,
Mount Sinai School of Medicine
Background and specific aims:
Cancer is a disease of the elderly; 50% of all cancer patients are over the age of 65,
and this number is growing rapidly as the population ages. LC patients experience
more debilitating symptoms than other cancer patients and better approaches to
symptom management are needed in this population. With the increasing reliance on
outpatient care, spouses and intimate partners are playing a more critical role in the
care of cancer patients. However, the spousal caregivers of LC patients are also likely
to be elderly and LC couples often leave the hospital with knowledge deficits that can
impede effective symptom management and care. Currently, there are no programs
that: a) take a couples’ approach to LC pain and symptom management; b) provide
practical strategies couples can use to discuss cancer-related symptoms and concerns;
and c) are designed to specifically address the pain/symptom management needs of
older LC patients and their partners.
Thus, the specific aims of this study are to:
1) Use focus groups to develop and refine a couple-focused intervention for
older lung cancer (LC) patients and their partners that prepares and educates
couples about LC symptoms, teaches them techniques for effective symptom
management and home care, and teaches communication skills that couples
can use to effectively problem-solve cancer-related concerns and coordinate
care.
2) Pilot test the intervention in a small randomized controlled trial (RCT) vs. a
usual care control group and to explore whether couples in the intervention
group experience better patient (i.e., symptom burden, symptom distress,
functional disability, general QOL), partner (caregiver strain, competence,
QOL), and relationship outcomes (i.e., relationship satisfaction and intimacy).
The study consists of 2 parts. Part 1 uses 4 focus groups comprising 30 LC patients
and their partners to develop and refine a symptom management intervention for
older LC couples. Preliminary intervention content is based on Dr. Badr’s previously
published studies of couples’ psychosocial adjustment to LC and her research on pain
in advanced cancer. The proposed intervention will encourage couples to view LC as
a ‘we’ disease, work together as a team to problem-solve and effectively manage
symptoms at home, and openly and supportively communicate about both the
practical and emotional challenges that can arise as LC progresses. Through its focus
on communication and the coordination of care between patients and their partners,
the goal of the intervention is to improve patient (i.e., symptom burden, symptom
distress, general QOL), partner (caregiver strain, competence, QOL), and relationship
outcomes (i.e., relationship satisfaction and intimacy) in LC. Part 2 will pilot test the
intervention in a small randomized controlled trial (RCT) vs. a usual care control
group (50 LC couples; 25 couples in each group). Thus, the proposed study will
provide estimates of intervention feasibility, acceptability, and preliminary efficacy
that will inform planning and provide power and sample size calculations for future
larger trials. By taking a coordinated approach to symptom management in LC,
teaching communication skills, and addressing the concerns of both partners, the
proposed intervention may provide maximum benefit and greatly facilitate the
symptom management and adaptation of both elderly LC patients and their spousal
caregivers.
Project 3: Palliation of Depression in Nursing Home Residents with Serious
Illness: A Non-pharmacological Approach
Principal investigator: Joann P. Reinhardt, PhD, Jewish Home Lifecare Institute on
Aging
Co-Investigator: Amy Horowitz, DSW, Department of Social Work, Fordham
University
Background and specific aims.
Geriatric patients residing in long-term care (LTC) facilities are typically
characterized by serious illness, poor life expectancy, and high symptom burden,
attributes which parallel those of palliative care patients across health care settings.
Among the most distressing symptom clusters for both residents and their family is
the experience of significant depressive symptomatology, a common mental health
comorbid condition associated with serious chronic illness in later life. The
consequences of untreated depression can be devastating and include both the
amplification of pain and symptom distress, as well as increased difficulty in treating
these symptoms, along with poor quality of life, and impaired capacity for pleasure,
meaning, and connection with others. Yet, both palliative care interventions, in
general, and treatments for depression, in particular, lack an evidence-base relevant to
the nursing home population, and remain largely inadequate to the need in LTC. The
treatment of first choice for depression in nursing homes is typically antidepressant
medication. However, the complexity of managing multiple concurrent serious
illnesses, along with problems associated with polypharmacy, call for greater
consideration of non-pharmacological, psychotherapeutic interventions, and in
particular cognitive therapeutic interventions appropriate for residents with no or mild
cognitive impairments, who continue to comprise 25-30% of the nursing home
population. Yet, randomized trials of psychotherapy in long term care are largely
lacking. This proposed pilot is a feasibility study of Problem Solving Therapy (PST)
among 40 nursing home patients to treat subsyndromal depression in patients with
serious life-threatening conditions who reside in LTC facilities. The specific aims of
this study are:
1) To demonstrate PST implementation fidelity (recruitment, acceptance, and
adherence to the protocol) within a nursing home setting.
2) To identify the potential of PST for nursing home residents with serious
chronic illness and subthreshold depression relative to: (a) Primary outcomes
of depression remission and clinically significant reductions in depressive
symptoms; and (b). Secondary outcomes of symptom distress (pain, fatigue).
3) To estimate the effect size of the PST intervention compared to Usual Care
with Social Contact for primary and secondary outcomes.
Findings from this study will contribute to the knowledge base on treating emotional
disorders in palliative care and provide the pilot data needed for the design of a larger
scale, multi-site study of PST in LTC. This study is innovative in several ways. First,
it targets older adults with subsyndromal and minor (rather than major) depression,
for who non-pharmacological approaches may be more appropriate but for which
limited effectiveness evidence is available. Second, while there is evidence
supporting the effectiveness of PST with depressed elders among primary, acute, and
home care patients, no prior research has tested the application of this manualized
psychotherapeutic program with a nursing home population. Third, in addition to
primary outcome measures of depression remission and symptom reduction, the team
is also examining secondary effects of PST on reduction of pain and fatigue which are
both key targets of palliative care and symptoms that can be exacerbated by
depression. These data will inform the development of a larger study to test the effect
of this nonpharmacological treatment for subthreshold depression and symptom
distress in this complex, medically ill population.
III. Career Development
Not applicable as Pepper grant was funded last year.
IV. Publications
1. Kelley AS, Meier DE. Palliative Care: A Shifting Paradigm. New England Journal of
Medicine. 363(8):781-782, August 19, 2010.
2. Smith CB, Kelley AS, Meier DE. Evidence for New Standard of Care in Non-Small Cell
Lung Cancer Patients. Seminars in Thoracic and Cardiovascular Surgery. (in press)
3. Kelley AS, Ettner SL, Morrison RS, Wenger NS, Sarkisian CA. Determinants of
Treatment Intensity in the Last 6 Months of Life: The Importance of Patient
Characteristics. (provisionally accepted, Annals of Internal Medicine).
4. Ko F. The clinical care of frail, adult. Clinics in Geriatric Medicine. 2011 Feb;27(1):89100.
5. Ornstein K, Smith KL, Foer DH, Lopez-Cantor T, Soriano T. To the hospital and back
home again: A Nurse Practitioner-based transitional care program for the hospitalized
homebound. Journal of the American Geriatrics Society. 2011; 59: 544-551.
6. Garrido MM, Kane RL, Kaas M, Kane RA. Use of mental health care by communitydwelling older adults. JAGS. 2011; 59(1), 50-56.
7. Garrido MM, Hash-Converse JM, Leventhal H, Leventhal EA. Stress and Chronic
Disease Management. In Contrada RJ, Baum AS, eds. The Handbook of Stress Science:
Psychology, Biology, and Health. New York: Springer; 2010.
8. Gelfman L, Morrison RS. Unavailability of Pain Medicines in Minority Neighborhoods
and Developing Countries. In: Incayawar M, Todd K, eds. Culture, Brain and Analgesia:
Understanding and Managing Pain in Diverse Populations. Oxford University Press,
Expected 2012
9. Kelley AS, Ettner SL, Morrison RS, Du Q, Wenger NS, Sarkisian CA. Determinants of
Medical Expenditures in the Last 6 Months of Life. Ann Intern Med 2011 (154):235-242
10. Leipzig RM, Whitlock EP, Wolff TA, Barton MB, Michael YL, Harris R, Petitti D, Wilt
T, Siu AL, for the U.S. Preventive Services Task Force Geriatric Workgroup –
Reconsidering the Approach to Prevention Recommendations for Older Adults. Ann
Intern Med 2010;153(12):809-814
11. Carlson MDA, Bradley EH, Du Q, Morrison RS. Geographic Access to Hospice in the
United States. J Palliat Med 2010;13(11):1331-1338
12. Carlson MDA, Lim B, Meier, DE – Strategies and Innovative Models for Delivering
Palliative Care in Nursing Homes J Am Med Dir Assoc 2011 Feb;12(2):91-8.
Mount Sinai Recognition and Awards
Mount Sinai Ranked #1 – Best Hospital for Geriatrics. Mount Sinai Hospital was one of
nearly 5,000 that U.S. News evaluated for its “Best Hospitals” rankings. U.S. News & World
Report July 15, 2010
http://health.usnews.com/best-hospitals/rankings/geriatric-care
Albert L. Siu, MD, MSHS –
Elected to the Board of Directors of the Visiting Nurse Service of New York.
Diane E. Meier, MD, FACP –
Presented with the Carol Selinske Founder’s Award for her “outstanding efforts on behalf
of hospice, palliative care and the needs of the terminally ill in New York State.”
Hospice & Palliative Care Association of New York State. Albany May 20, 2011
Received the Contemplative Care Award, which honors leaders in the field of
compassion and contemplative care. New York Zen Center for Contemplative Care.
April 28, 2011
Emphasis on patient will help health-care reform succeed. The Tennessean February 19,
2011
http://www.tennessean.com/article/20110220/OPINION/102200348/Emphasis-patientwill-help-health-care-reform-succeed
Hospitals Increasingly Offer Palliative Care. Washington Post March 28, 2011
http://www.washingtonpost.com/national/hospitals-increasingly-offer-palliativecare/2011/03/24/AFuFAeqB_story.html
Palliative Care Consultations: An Answer to Medicaid's Woes. GeriPal March 8, 2011
http://www.geripal.org/2011/03/palliative-care-consulations-answer-to.html
Interview, The Open Mind on PBS. February 26, 2011
http://www.thirteen.org/openmind/health/palliative-medicine-care-versus-cure/2038/
What Is Palliative Care? WebMD January 31, 2011
http://www.webmd.com/a-to-z-guides/features/what-is-palliative-care
R. Sean Morrison, MD –
The Gerontology Hall of Fame: 14 individuals who merit a “hall of fame” status in this
field. e-Med News. February 6, 2011
Palliative Care Consultations: An Answer to Medicaid's Woes. GeriPal March 8, 2011
http://www.geripal.org/2011/03/palliative-care-consulations-answer-to.html
Study: Third Of Cancer Patients On Opioids Suffer Cognitive Problems. USA Today
March 6, 2011
http://www.usatoday.com/yourlife/health/medical/2011-03-05-opioids_N.htm
Study Finds Third of Cancer Patients on Opioids Are Confused. HealthDay March 3,
2011
http://health.usnews.com/health-news/family-health/cancer/articles/2011/03/03/studyfinds-third-of-cancer-patients-on-opioids-are-confused
Rosanne M. Leipzig, MD, PhD –
Dr. Leipzig has been selected to receive a Career Achievement Award from the Institute
for Medical Education (IME). Selected from a large pool of qualified teachers, she was
chosen by colleagues, learners, and a faculty committee, who felt Dr. Leipzig
demonstrated exceptional skill and dedication as a teacher and has made important
contributions to the educational activities at Mount Sinai and its affiliate hospitals. April,
2011
Dr. Leipzig received an invitation to join the Editorial Board of Annals of Internal
Medicine, a journal of the American College of Physicians (ACP). April, 2011
Kenneth Boockvar, MD –
Dr. Boockvar (mentor) and Dr. Karen Abrashkin (resident) were winners of a 2010
Samuel L. Bronfman Department of Medicine Advancing Clinical Excellence in Medicine
(ACEM) grant for “Inter-hospital Transfers in a Department of Internal Medicine: Effects
of Pre-transfer Communication on Resource Utilization.” MSSM, November, 2010
University of California, Los Angeles (UCLA)
Claude D. Pepper Older Americans Independence Center
David B. Reuben, M.D., Principal Investigator
David Geffen School of Medicine at UCLA
Multicampus Program in Geriatric
Medicine & Gerontology
10945 Le Conte Avenue, Suite 2339
Los Angeles, CA 90095-1687
Phone: 310/825-8253
FAX: 310/794-2199
E-Mail: [email protected]
I.
DESCRIPTION OF CENTER
The UCLA Claude Pepper Older Americans Independence Center (OAIC) is designed to
maintain and restore the independence of older persons. The Center’s theme, “Developing
Interventions to Maintain Independence and Understanding Mechanisms of Successful
Interventions” emphasizes research that builds bridges between basic biomedical science and
clinical science.
In the UCLA OAIC paradigm, basic biomedical research informs clinical research and clinical
research informs basic biomedical research. Accordingly, the UCLA OAIC supports research
that links these two types of research in both directions by 1) examining mechanisms underlying
successful clinical interventions and 2) developing new basic science approaches that will lead to
clinical interventions.
The Center stimulates scientific discovery through 4 Research Cores (Recruitment, Research
Operations, Analysis and Cost-effectiveness, and Inflammatory Biology), a Pilot and Exploratory
Studies Core, a Research Career Development Core, and a Leadership/Administrative Core.
Research Cores provide 4 levels of support (consultation, short-term, ongoing, and partnership
on new projects) for external projects and internal OAIC activities.
The UCLA OAIC specific aims are:
1) To provide intellectual leadership and innovation for geriatrics and aging research on the
Center’s theme and related research
2) To stimulate translational links between basic and clinical research, with an emphasis on
inflammation
3) To facilitate and develop novel multidisciplinary research
4) To stimulate incorporation of emerging technologies
5) To serve as source of advice and collaboration to other institutions
6) To provide career development of future research leaders
II.
A.
RESEARCH, RESOURCES AND ACTIVITIES
CORES
A1. Leadership/Administrative Core
A2. Research Career Development Core
A3. Pilot and Exploratory Studies Core
A1. Leadership/Administrative Core (LAC)
Core leader:
David B. Reuben, MD
Archstone Foundation Chair and Professor of Medicine
David Geffen School of Medicine at UCLA
10945 Le Conte Avenue, Suite 2339
Los Angeles, CA 90095-1687
Ph: 310-825-8253
Fax: 310-794-2199
Email: [email protected]
Core Co-leader:
Debra Saliba, MD, MPH
Director, The Anna and Harry Borun Center for Gerontological Research
Email: [email protected]
Administrator:
Janet C. Frank, DrPH
UCLA Multicampus Program in Geriatric Medicine and Gerontology (MPGMG)
Email: [email protected]
Administrative Manager:
Lucio Arruda
Email: [email protected]
The Leadership/Administrative Core (LAC) provides support for planning, organizational,
evaluation, and administrative activities related to the other OAIC Cores and to the OAIC as a
whole. It monitors, stimulates, sustains, evaluates and reports progress towards the Center’s
overall goals. To do so, the LAC has established eight specific aims:
(1)
(2)
(3)
(4)
to provide day-to-day management of the UCLA OAIC
to provide fiscal management for the UCLA OAIC
to provide administrative oversight for internal quality control of ongoing research
to review utilization of UCLA OAIC resources by other OAIC cores, including
reallocation of resources within and among cores
(5) to create linkages between UCLA OAIC Cores/investigators and other UCLA researchers
whose work relates to the theme and mission of the Center, particularly those that focus
on translational research
(6) to solicit applications for new career development awardees (CDAs), pilots, and
Developmental Projects (DPs) and coordinate the review process for these
(7) to ensure communication, coordination and collaboration among the UCLA OAIC cores,
(intra-OAIC) and between the UCLA OAIC and other OAICs (inter-OAIC) and
(8) to maintain contact with NIA staff, the national OAIC Coordinating Center and the
External Advisory Committee, and External Selection Panel.
A2. Research Career Development Core (RCDC)
Core leader:
Theodore J. Hahn, MD
Deputy Director, Geriatric Research Education and Clinical Center (GRECC)
VA Greater Los Angeles Healthcare System
11301 Wilshire Blvd., (11G)
Los Angeles, CA 90073
Ph: 310-268-4110
Fax: 310-268-4842
Email: [email protected]
Core co-leaders:
Alison A. Moore, MD, MPH
David Geffen School of Medicine at UCLA
Email: [email protected]
Catherine Sarkisian, MD
David Geffen School of Medicine at UCLA
Email: [email protected]
Thomas Yoshikawa, MD
David Geffen School of Medicine at UCLA
Email: [email protected]
The goal of the Research Career Development Core (RCDC) is to train junior faculty members to
become future academic leaders in translational basic, clinical and health services research
directed toward improving the independence of older persons. Related goals involve attracting
new faculty from various disciplines into aging research and serving as a resource in aging
education and research to the UCLA community.
Features of the RCDC include:
(1) a Career Development Award (CDA) program comprised of up to 3 junior faculty members
and their mentorship committees in a structured interdisciplinary program that provides
integrated training in translational mechanistic and outcomes research, and promotes faculty
career development;
(2) an organized program of instruction to enhance the research training of all junior faculty and
fellows, the latter representing our future junior faculty;
(3) a Research Development Mentorship Panel, comprised of senior faculty with a wide range of
expertise, to provide junior faculty awardees with individualized interdisciplinary training in
translational research and career development; and
(4) an interdisciplinary RCDC Committee to monitor the progress of RCDC awardees and assure
that the RCDC contributes to the enhancement of aging-related research and training at UCLA.
CDA funding generally starts July 1 and requests for applications are announced in the winter.
A3. Pilot and Exploratory Studies Core (P/EC)
Core leader:
Gail Greendale, MD
Professor of Medicine and Obstetrics & Gynecology
David Geffen School of Medicine at UCLA
10945 Le Conte Avenue, Suite 2339
Box 951687
Los Angeles, CA 90095-1687
Ph: 310-825-8253
Fax: 310-794-2199
Email: [email protected]
Core co-leaders:
Rita B. Effros, PhD
David Geffen School of Medicine at UCLA
Email: [email protected]
Peifeng Hu, MD
David Geffen School of Medicine at UCLA
Email: [email protected]
The purpose of the UCLA P/EC is to promote innovative basic and clinical research, conducted
by collaborating teams of junior and senior investigators through pilots and exploratory studies,
that falls within the UCLA OAIC’s research theme of “Developing Interventions to Maintain
Independence and Understanding Mechanisms of Successful Interventions.” These studies will
serve as the basis for additional studies that help the UCLA OAIC fulfill its mission.
The UCLA OAIC’s emphasis is on research that bridges basic biomedical research and clinical
science. Although the path from basic to applied medical science is generally conceived to move
unidirectionally from basic research to applied health, in fact, communication in both directions
is essential: basic biomedical research must inform clinical research and clinical research must
inform basic biomedical research.
Pilot funding generally starts July 1 and requests for proposal are announced in the fall. The total
number of pilot projects to be funded will be determined by the total annual budget of the P/EC
core and the budgets of the selected pilot projects.
In January 2008, the UCLA P/EC instituted a new pilot grant mechanism, the “Rapid Grants
Program.” The goal of the rapid grants program is to provide small-to-moderate sized funding
($500 to $10,000) to advance the independent research careers of junior faculty and advanced
trainees. A rolling application process is used for this mechanism and requests for proposals are
announced in the winter.
B.
RESEARCH CORES
B1. Analysis/Cost-Effectiveness Core (A/CE)
B2. Inflammatory Biology Core (IBC)
B3. Recruitment Core (RC)
B4. Research Operations Core (ROC)
Levels of service provided by the UCLA OAIC Research Cores
•
Consultation (e.g., providing up to several hours of advice, reading a paper or a proposal).
The wealth of resources in the UCLA OAIC and diversity of viewpoints have provided a
rigorous level of internal review of publications and proposals. This level of support is
provided to many investigators who are directly supported by the OAIC and others whose
research may relate to the OAIC’s theme and goals.
•
Short-term (e.g., up to a couple days of consultation, performing assays).
For selected projects and pilots, Research Cores will provide more in-depth services such as
conducting specific analyses and performing assays. Decisions about whether these can be
supported through a Core’s basic budget versus requiring additional funds will be made on a
case-by-case basis depending upon the cost of the request, potential to lead to future funding
for OAIC-related research, and level of investigator (junior faculty will receive priority for
uncompensated core support).
•
Ongoing or long-term support (e.g., ongoing, part of the project team).
In general, when ongoing support from a core is needed by a project, the effort of core
personnel and resources will be budgeted as part of the research proposal or additional funds
will be sought. In these instances, investigators will gain the experience, efficiency, and
reliability of core services by purchasing them as part of their budget. Some exceptions to the
rule that studies must bear these costs will be made to support pilots and junior faculty
conducting small studies.
•
Partnership on new proposals
Investigators may enlist OAIC Cores as partners to perform key functions of new research
and introduce OAIC-related research questions and hypotheses.
•
Research Services Funding Program
Research support of up to $10,000 is provided to small projects by UCLA faculty members
conducting aging research for the use of services provided by the OAIC Research Cores
(Analysis/Cost-Effectiveness, Inflammatory Biology, Recruitment and Research Operations).
In this mechanism, the funds are transferred to the OAIC research core providing support, not
the investigator. A rolling application process is used and requests for proposals are
announced once a year.
B1. Analysis/Cost-Effectiveness Core (A/CE)
Core leader:
Emmett Keeler, PhD
RAND Corporation
1776 Main St., Box 2138
Santa Monica, CA 90407-2138
Ph: 310-393-0411 ext7239
Fax: (310) 260-8155
Email: [email protected]
Core co-leaders:
John Adams, PhD
RAND Corporation
Email: [email protected]
Ron Hays, PhD
UCLA Dept. of Medicine
Email: [email protected]
Arun Karlamangla, MD
UCLA Dept. of Medicine
Email: [email protected]
There is concern over the costs of providing services to improve the health and independence of
the nation’s elderly. Interventions that improve health are also evaluated in terms of the
resources needed to so. This research core aims to advise and work with the other projects and
trainees of the center on the methodological issues and problems specific to the design and
statistical analysis of studies of interventions, assessment of their immediate and longer-term
outcomes, preferences, and costs. The A/CE aims to maximize the validity and value of those
studies through the application of appropriate state-of-the-art statistical methods.
B2. Inflammatory Biology Core (IBC)
Core leader:
Michael Irwin, MD, PhD
Professor of Psychiatry and Biobehavioral Sciences
David Geffen School of Medicine at UCLA
300 Medical Plaza, Suite 3109
BOX 957076
Los Angeles, CA 90095-7076
Ph: 310-825-8281
Fax: 310-794-9247
Email: [email protected]
Core co-leaders:
Elizabeth Breen, PhD
David Geffen School of Medicine at UCLA
[email protected]
Steven Cole, PhD
Associate Professor of Hematology-Oncology
David Geffen School of Medicine at UCLA
Email: [email protected]
Otoniel Martinez-Maza, PhD
Professor of Obstetrics/Gynecology
David Geffen School of Medicine at UCLA
Email: [email protected]
Inflammatory biology plays a central role in illness and disability among older people. The
OAIC IBC at UCLA provides intellectual and technical support for the analysis of inflammatory
dynamics in OAIC research programs. In addition to conventional blood-based measures of
inflammatory markers, the IBC also provides extensive molecular biology infrastructure for
mapping upstream signaling processes that cause aberrant inflammation, and for defining the
down-stream impact of inflammatory signaling on target issues.
The OAIC IBC works to generate new technical approaches for assessing molecular bases of
inflammatory signaling during aging, measuring functional impacts of genetic polymorphisms,
and monitoring the activity pro-inflammatory cytokines and hormones using genomics-based
biomarkers. The OAIC IBC includes multi-disciplinary intellectual support (behavior, genetics,
and immunology), vertical integration of inflammatory biology into the full range of research
program development, training in molecular analyses of inflammation, and development of new
strategies for assessing the sources and targets of inflammatory signals in aging individuals.
B3. Recruitment Core (RC)
Core leader:
Carol M. Mangione, MD
Professor of Medicine
David Geffen School of Medicine at UCLA
911 Broxton Plaza
Los Angeles, CA 90095-1736
Ph: 310-794-2298
Fax: 310-794-0723
Email: [email protected]
Core co-leaders:
Loretta Jones, MA
Healthy African American Families (HAAF)
Email: [email protected]
Keith Norris, MD
Charles R. Drew University of Medicine and Science
Email: [email protected]
Michael Rodriguez, MD
David Geffen School of Medicine at UCLA
Email: [email protected]
The UCLA OAIC Recruitment Core (RC) enhances participation of older persons from diverse
communities who are at greatest risk for functional decline and poor health outcomes in studies
by providing a structure for sharing expertise in this essential area with a larger group of faculty
who are conducting clinical research with the UCLA OAIC. Given the disproportionate burden
of chronic diseases and functional impairment among minority elders, and consistent with the
theme of the UCLA OAIC, it is critical to have participation of older African Americans and
Latinos in the studies linked to the UCLA OAIC so that the interventions developed to maintain
independence are generalizable to the populations most in need of them. Additionally, inclusion
of minority elders in studies designed to examine the biological mechanisms of successful
interventions provides the data needed to examine whether these mechanisms vary by race and
ethnicity.
B4. Research Operations Core (ROC)
Core leader:
Teresa E. Seeman, PhD
Professor of Medicine/Geriatrics
David Geffen School of Medicine at UCLA
10945 Le Conte Avenue, Suite 2339
Box 951687
Los Angeles, CA 90095-1687
Ph: 310-825-8253
Fax: 310-794-2199
Email: [email protected]
Core co-leader:
Heather McCreath, PhD
Researcher
Department of Medicine/Division of Geriatrics
David Geffen School of Medicine at UCLA
Email: [email protected]
The OAIC Research Operations Core (ROC) is an extension and expansion of the Data
Management Core funded through the previous OAIC grant. To contribute to the UCLA OAIC’s
twin goals of promoting development of interventions to maintain independence and
understanding the biological mechanisms contributing to successful interventions, the ROC
provides state-of-the-art data collection and data management services to support the successful
implementation of OAIC- and externally-funded projects that address questions relevant to the
UCLA OAIC’s themes and mission.
ROC services encompass consultations during proposal preparation as well as assistance in
development and implementation of data collection and data management protocols for funded
research projects. Specific data collection and data management services available through the
ROC include advising investigators on data collection tools; developing and maintaining tracking
systems to monitor subject recruitment and scheduling of data collection activity; data entry,
verification, and data cleaning services; and providing data documentation for all project
databases.
The ROC also offers custom programming to meet special project needs and run regular training
workshops for junior faculty and research staff, focusing on theoretical and practical aspects of
research operations.
C.
PILOTS
YEAR 20 (JULY 2010 – JUNE 2011)
Identification of the High-Affinity Endothelial Cell Signaling Receptors for Pigment
Epithelium-Derived Factor
Hui Sun, Ph.D.
Professor of Physiology, David Geffen School of Medicine at UCLA
Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly in the
United States, currently affecting more than 10 million Americans. Vision loss can severely limit
the independence of older Americans. The aging of the population, especially the Baby Boomer
generation, will further substantially increase the incidence of this aging disease, and new
treatments are desperately needed. Pathological angiogenesis is the primary cause of legal
blindness in AMD. Pigment epithelium-derived factor (PEDF) is a remarkably effective and
specific endogenous antiangiogenic factor with tremendous therapeutic value, but the difficulties
in producing and delivering protein-based drugs have seriously limited its therapeutic
application. This project aims to identify the endothelial cell signaling receptors for PEDF using
novel technical strategies. This fundamental knowledge will greatly facilitate the development of
new therapies for AMD. As demonstrated by the enormous clinical success of targeting Gprotein coupled receptors, receptors are ideal therapeutic targets to treat human diseases. More
specific and effective antiangiogenic therapies will benefit the treatment of not only AMD but
also other angiogenesis-based diseases such as cancer and inflammatory disorders that lead to
disability of the elderly.
Examining genome-wide alterations in gene expression in long-lived Drosophila mutants
David W. Walker, PhD
Assistant Professor of Physiological Science, UCLA
Aging is due to the accumulation of damage over time that affects the function and survival of
the organism; however, it has proven difficult to infer the relative importance of the many
processes that contribute to aging. Alterations in mitochondrial energy metabolism may be
particularly important because it affects a wide range of cellular processes, and will have
widespread consequences for other metabolic systems within the cell.
Our lab is using the powerful genetics of the fruit fly Drosophila to better understand the role of
mitochondrial electron transport chain (ETC) function in modulating the aging process.
Recently, we reported the results of an in vivo RNA interference (RNAi) screen to identify ETC
genes important for longevity (Copeland et al., 2009). In performing this screen, we discovered
that RNAi of five genes encoding components of mitochondrial respiratory complexes I, III, IV,
and V can retard the aging process in flies. Moreover, RNAi of certain ETC genes in neuronal
tissue alone was sufficient to delay aging in the whole animal. Here, we propose to extend these
studies to better understand the underlying molecular mechanisms at play. We will use DNA
microarray technology to examine alterations in gene expression, at the whole-genome level, in
long-lived flies. Upon identifying downstream molecular targets of ETC-mediated longevity we
will next examine genetic interactions between these genes and ETC genes. This approach will
facilitate the identification of novel genes and associated genetic pathways important for ETCmediated longevity.
Histone Acetylation and Cognitive Aging
Cui-Wei Xie, PhD, MD
Professor, Department of Psychiatry and Biobehavioral Sciences and Semel Institute for
Neuroscience, UCLA
Studies in humans and rodents show aging-related deficits in cognitive function such as learning
and memory. The cellular basis for such deficits is less clear. Our goals are to determine key
synaptic and signaling events responsible for cognitive aging and to explore potential
therapeutics for retaining cognitive function during aging. We are particularly interested in agedependent changes in epigenetic regulation of gene expression and resulting alterations of
synaptic function and structure. Our preliminary studies in old rodents demonstrated agedependent impairement in hippocampal long-term potentiation (LTP), a synaptic model of
learning and memory. The LTP impairment was closely associated with reductions in histone
acetylation and brain-derived neurotrophic factor (BDNF) lelvels in hippocampal neurons.
Increasing histone acetylation with inhibitors of histone deacetylase (HDAC) enahnced BDNF
levels, and rescued LTP in a transcription- and BDNF-dependent manner. We therefore propose
that age-dependent declines in chromatin histone acetylation and BDNF expression play key
roles in aging-related hippocampal dysfunction; drugs that increase histone acetylation can
enhance BDNF expression and signaling to improve synaptic function and memory in aging
animals. We will test these hypotheses in three specific aims using a combination of
electrophysiological, biochemical, neural imaging and behavioral approaches.
Aim 1. To determine whether the decline in histone acetylation is responsible for reduced BDNF
expression and LTP deficits in aging rats, and how aging may affect activity of two BDNFregulated protein kinases, calcium/ calmodulin-dependent protein kinase II (CaMKII) and
extracellular signal-regulated kinases (Erk), both essential for LTP and memory.
Aim 2. To examine whether the density of dendritic spines is reduced in aging hippocampi and
whether HDAC inhibitors and BDNF can counter aging effect to increase spine density.
Aim 3. To detetmine whether aging-related deficits in behavioral learning and memory,
measured by fear conditioning, can be rescued by HDAC inhibitors via enhancement of BDNF
expression. These studies will provide novel information for epigenetic regulation of cognitive
aging and interventions.
YEAR 01 TO YEAR 19 PILOTS (JULY 1991 – JUNE 2010)
Validation of a Kilocalorie Expenditure Questionnaire (Kalculate) Employed in a Walking
Program – Year 01 (1991-92)
David A. Leaf, MD, MPH – [email protected]
Adjunct Associate Professor of Medicine
Sleep and Behavior in the Impaired Nursing Home Resident – Years 01-03 (1991-94)
Cathy A. Alessi, MD – [email protected]
Professor of Medicine
Walking Disabilities in the Elderly Board and Care Population – Year 02 (1992-93)
Nancy Harada, PhD, PT – [email protected]
Adjunct Professor of Medicine
Non-Pharmacologic Pain Management – Year 02 (1992-93)
Bruce A. Ferrell, MD – [email protected]
Professor of Medicine
The Effects of a Six-Month Walking Program on Functional and Biomedical Markers of
Health in Nursing Home Residents – Year 03 (1993-94)
Priscilla Gilliam MacRae, PhD
Professor of Sports Medicine, Pepperdine University - 310-456-4162
Investigating the Bone-Trophic Mechanisms of a Weighted Vest - Year 03 (1993-94)
Gail A. Greendale, MD – [email protected]
Professor of Medicine
Exploring the Prevalence of Menopausal Symptoms and Defining the Role of Estrogens
and Androgens in Sexual Function Among Postmenopausal Breast Cancer Survivors –
Year 04 (1994-95)
Patricia A. Ganz, MD – [email protected]
Professor of Public Health and Medicine
Gail A. Greendale, MD - [email protected]
Professor of Medicine
Development of Methods in the Study of Costs, Efficacy and Satisfaction of Advance
Healthcare Directives – Year 04 (1994-95)
Alexander J. Tymchuk, PhD – [email protected]
Associate Professor of Psychiatry and Biobehavioral Sciences
Prospective Validation of a Prediction Rule for Improvement Following Cataract
Extraction Preparation of a Randomized Trial of Cost Effectiveness and Visual Functional
Outcome After Cataract Extraction Versus Non-Surgical Care – Year 04 (1994-95)
Carol M. Mangione, MD – [email protected]
Professor of Medicine
Enhancement of Influenza Vaccine Immunogenicity in the Elderly – Year 04 (1994-95)
Rita B. Effros, PhD – [email protected]
Professor of Pathology-Laboratory Medicine
Melatonin Levels and Sleep in Impaired Nursing Home Residents – Year 04-05 (1994-96)
Cathy A. Alessi, MD – [email protected]
Professor of Medicine
F. Eugene Yates, PhD - [email protected]
Professor, Medical Monitoring Unit
Immunodeficiency of Aging: Replicative Senescence of T Lymphocytes – Year 05 (1995-96)
Rita B. Effros, PhD – [email protected]
Professor of Pathology-Laboratory Medicine
Total Energy Expenditure and Cardiorespiratory Function in Frail Nursing Home
Residents – Year 05 (1995-96)
Holden MacRae, PhD - 310-456-4278
Associate Professor of Sports Medicine, Pepperdine University
Utility Assessment and Barriers to Randomization to Surgical vs Non-Surgical Care
Among Persons With Cataract – Year 05 (1995-96)
Carol M. Mangione, MD – [email protected]
Professor of Medicine
Dysregulation of Cytokine Balance of Antigen-Presenting Cells in Age-Related Immune
Dysfunction – Year 05 (1995-96)
Steven C. Castle, MD – [email protected]
Professor of Medicine
Age Associated Changes in Lymphocyte Apoptosis Triggered by Galectin-1 – Year 06
(1996-97)
Linda G. Baum, MD, PhD – [email protected]
Professor of Pathology and Laboratory Medicine
Age Defect in Antigen Presentation-T Cell Interaction to Tuberculosis – Year 06 (1996-97)
Takashi Makinodan, PhD – [email protected]
Professor of Medicine
Development and Preliminary Testing of a Nutritional Intervention for Older Persons With
Protein-energy Undernutrition – Year 06 (1996-97)
David B. Reuben, MD – [email protected]
Professor of Medicine
Fibronectin Alternate Splice Isoforms in Osteoarthritis – Year 07 (1997-98)
John H. Peters, MD - (916) 366-5332
Assistant Professor of Medicine in Residence, UC Davis School of Medicine
Preferences for Health Outcomes in Older Adults – Year 07 (1997-98)
Cathy D. Sherboune, PhD - 310-393-0411 x7216
Behavioral Scientist, Social Policy Department, The Rand Corporation
Validation of the Alcohol-Related Problems in the Elderly Survey (ARPS): A Screening
Measure for Identifying Harmful and Hazardous Drinking in Older Persons – Year 07
(1997-98)
Alison A. Moore, MD, MPH – [email protected]
Professor of Medicine
Effects of Oxidized Lipids on Osteogenic Potential of Marrow Stromal Cells – Year 08
(1998-99)
Farhad Parhami, PhD – [email protected]
Associate Professor of Medicine
ERT: Does it Protect Against Increase in HPA Axis Reactivity? – Year 08 (1998-99)
Teresa E. Seeman, PhD – [email protected]
Professor of Medicine
Effects of Testosterone Replacement Therapy on Alzheimer’s Disease Immunopathogenesis
– Year 08 (1998-99)
Verna R. Porter, MD – [email protected]
Assistant Clinical Professor, Department of Neurology; Chief, Division of Neurology,
UCLA/Santa Monica Medical Center
Developing Nursing Home Quality-of-Life Interventions Based on Preference and
Satisfaction Measures – Year 08 (1998-99)
John F. Schnelle, PhD - [email protected]
Director, Vanderbilt Center for Quality Aging
Sandra Simmons, PhD - [email protected]
Associate Professor, Vanderbilt University
Molecular Mechanism of Postmenopausal Osteoporosis – Year 09 (1999-2000)
Ichiro Nishimura, DDS, DMSc, DMD - [email protected]
Professor of Dentistry
Parathyroid Hormone Induces Novel Primary Response Genes in Osteoblasts –
Year 09 (1999-2000)
Sotirio Tetradis, DDS, PhD - [email protected]
Associate Professor of Dentistry
Biomechanics of Crashes, Injuries, and Protective Devices Among Elderly Occupants in
Motor Vehicle Crashes – Year 09 (1999-2000)
Corinne Peek-Asa, PhD – (319) 335-4895
Associate Professor of Public Health
Iowa Injury Prevention Research Center, University of Iowa
Estrogen Receptor Expression and Function in Human T Cells – Year 09 (1999-2000)
Rita B. Effros, PhD –[email protected]
Professor of Pathology-Laboratory Medicine
Development of an Intervention to Prevent Functional Decline among Community-residing
Older Minority Adults with Diabetes Mellitus – Year 09 (1999-2000)
Carol M. Mangione, MD – [email protected]
Professor of Medicine
Investigating Nutritional Care Staffing in Nursing Homes – Year 09 (1999-2000)
Shan Cretin, PhD - 310-393-0411 x7322
Senior Scientist, Health Program, RAND
Hatha Yoga to Improve Kyphotic Posture and its Complications – Year 10 (2000-2001)
Gail A. Greendale, MD – [email protected]
Professor of Medicine
A Measurement Protocol of Individualized Care in Nursing Homes – Year 10 (2000-2001)
Lené Levy-Storms, PhD – [email protected]
Assistant Professor, UCLA School of Public Affairs/Social Welfare
Social Control of Health Behaviors Among Older Adults – Year 10 (2000-2001)
Joan S. Tucker, PhD - 310-393-0411 x7519
Associate Behavioral Scientist, RAND
Estrogen/Telomerase Interaction in Normal Human T Cells – Year 11 (2001-2002)
Rita B. Effros, PhD – [email protected]
Professor of Pathology-Laboratory Medicine
The Effect of a Feeding Assistance Program to Improve Nutrition on Skin Health
Outcomes in Nursing Home Residents – Year 12 (2002-2003)
Barbara M. Bates-Jensen, PhD, RN – [email protected]
Adjunct Assistant Professor of Medicine
The Epidemiology of Kyphosis in Older Persons: A New Geriatric Syndrome? –
Year 12 (2002-2003)
Deborah M. Kado, MD, MS – [email protected]
Assistant Professor of Medicine
Effect of Alendronate on Structural Engineering Measures of Femoral Neck Strength in
the Fracture Intervention Trial – Year 12 (2002-2003)
Arun S. Karlamangla, MD, PhD – [email protected]
Assistant Professor of Medicine
The New ERA Pilot Study: Pilot Testing of an Intervention to Raise Physical Activity
Levels among Community-residing Older Adults by Raising Expectations Regarding Aging
Year 12 (2002-2003)
Catherine A. Sarkisian, MD, MSPH – [email protected]
Assistant Professor of Medicine
How Often do Physicians Address Cognitive Issues in Patients 75 and Older? –
Year 13 (2003-2004)
Joshua Chodosh, MD, MSHS – [email protected]
Assistant Professor of Medicine
Effect of Senescent T Cells on Bone Physiology - Year 13 (2003-2004)
Farhad Parhami, PhD – [email protected]
Associate Professor of Medicine
Translation of Feeding Assistance Interventions Into Daily Nursing Home Care Practice
Year 13 (2003-2004)
Sandra Simmons, PhD - [email protected]
Associate Professor, Vanderbilt University
Using Information Technology to Improve Care of Vulnerable Veterans –
Year 14 (2004-2005)
Constance H. Fung, MD, MSHS – [email protected]
Assistant Professor of Medicine
Therapeutic Potential of Demethylasterriquinone B1 (DAQ B1), a Small Molecule Insulin
Mimetic, in Alzheimer’s Disease – Year 14 (2004-2005)
Lixia Zhao, PhD (currently in medical school at Harvard)
Greg Cole, PhD – [email protected]
Professor of Medicine and Neurology
The Relationship Between Sleep and Inflammatory Markers Among Older Adults
Undergoing Post-Acute Rehabilitation – Year 15 (2005-2006)
Jennifer Martin, PhD – [email protected]
Assistant Researcher
Hepcidin Antagonists to Treat Anemia of Inflammation (Two-Year pilot: Year 16 and 17:
2006-2008)
Tom Ganz, MD, PhD – [email protected]
Professor of Medicine, David Geffen School of Medicine at UCLA
Novel Drugs for Age-Related Cognitive and Synaptic Deficits (Two-Year pilot: Year 16 and
17: 2006-2008)
Greg Cole, PhD – [email protected]
Professor of Medicine, David Geffen School of Medicine at UCLA
Upper-Extremity Function Following Yoga for Hyperkyphosis (Two-Year pilot: Year 16
and 17: 2006-2008)
George Salem, PhD – [email protected]
Associate Professor of Biokinesiology & Physical Therapy, USC School of Medicine
Yoga for Older Breast Cancer Survivors with Fatigue (Two-Year pilot: Year 16 and 17:
2006-2008)
Julie Bower, PhD – [email protected]
Assistant Professor of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine
at UCLA
Identifying predictors of transitions between physical activity and inactivity among
community-dwelling older persons – Year 17 (2007-2008)
O. Kenrik Duru, MD – [email protected]
Assistant Professor of Medicine, David Geffen School of Medicine at UCLA
Study to Evaluate the Effect of Aging on CD8 T cell Phenotypes in HIV-infected
Individuals Receiving Potent Antiretroviral Therapy – Year 17 (2007-2008)
Ronald Mitsuyasu, MD - [email protected]
Professor of Medicine/Hematology and Oncology, David Geffen School of Medicine at UCLA
Investigation of the Pathophysiology of bisphosphonate related osteonecrosis of the jaws –
Year 17 (2007-2008)
Tara L. Aghaloo, DDS, MD, PhD - [email protected]
Assistant Professor, Oral and Maxillofacial Surgery, UCLA School of Dentistry
Development of Puromycin Sensitive Aminopeptidase (PSA) activity for the small molecule
high-throughput screen (HTS) - Year 17 (2007-2008)
Stanislav Karsten, PhD - [email protected]
Assistant Professor of Neurology, David Geffen School of Medicine at UCLA
Validation of Multiplex Analyses in the Inflammatory Biology Core Laboratory – Year 17
(2007-2008)
Mary Frances O’Connor, PhD - [email protected]
Assistant Professor of Psychiatry and Biobehavioral Sciences
David Geffen School of Medicine at UCLA
Epigenetic Control of Neural Repair in the Aged Brain after Stroke – Two Year Pilot (year
17 and 18: 2007-2009)
Stanley Thomas Carmichael, MD, PhD – [email protected]
Associate Professor of Neurology, David Geffen School of Medicine
UCLA Mind/Body Study: Managing stress and social ties for healthy aging Two Year Pilot
(year 17 and 18: 2007-2009)
Sarosh Motivala, PhD – [email protected]
Assistant Professor of Psychiatry and Biobehavioral Sciences
David Geffen School of Medicine at UCLA
Nutraceutical intervention in the Nrf2-mediated anti-oxidant and anti-inflammatory
pathway to suppress inflamm-aging in mice - Two Year Pilot (year 17 and 18: 2007-2009)
Andre Nel, MD, PhD – [email protected]
Professor of Medicine/NanoMedicine, David Geffen School of Medicine at UCLA
Enhancing Physiological Function by Removal of Damaged Proteins from Aging Cells –
Year 18 (2008-2009)
Steven G. Clarke, PhD - [email protected]
Professor Chemistry and Biochemistry and Director
UCLA Molecular Biology Institute
Oxidative Stress Induces Age-related Osteoporotic Bone Loss by Inhibiting the Hedgehog
and Notch Signaling Pathways – Year 18 (2008-2009)
Woo-Kyun Kim, Ph.D. – [email protected]
Assistant Researcher, Department of Medicine, UCLA
Farhad Parhami, Ph.D.
Associate Professor of Medicine, UCLA
Immunophenotyping of regulatory T cells in young and older RA patients - Year 18 (20082009)
Ram P. Singh, PhD – [email protected]
Associate Researcher, Department of Medicine/Rheumatology
David Geffen School of Medicine at UCLA
Vasoactive intestinal peptide (VIP) restores age-related sleep and circadian dysfunctions Year 18 (2008-2009)
Takahiro Nakamura, PhD - [email protected]
Postdoctoral Scholar
UCLA Department of Psychiatry
Development of a flow cytometry method for sensitive detection of multifunctional varicella
zoster virus-specific T-cells - Year 18 (2008-2009)
Stoyan Dimitrov, PhD – [email protected]
Postdoctoral Fellow
UCLA Department of Psychiatry
The Role of Hedgehog Signaling in Spinal Fusion - Year 18 (2008-2009)
Jeong-Hyun Yoo, MD, Postdoctoral Scholar – [email protected]
Farhad Parhami, PhD, Associate Professor of Medicine/Cardiology
Jeffrey Wang, MD, Associate Professor of Orthopaedic Surgery and Neurosurgery
UCLA David Geffen School of Medicine
Identification of Transcriptional Regulators of Puromycin Sensitive Aminopeptidase - Year
18 (2008-2009)
Liubov Parfenova, PhD, Postdoctoral Scholar - [email protected]
Stanislav Karsten, PhD
Assistant Professor of Neurology
David Geffen School of Medicine at UCLA
Identification of pre-malignant serum profiles in mature HIV-infected individuals – Year
19 (2009-2010)
Elizabeth Crabb Breen, PhD – [email protected]
Associate Professor of Psychiatry and Biobehavioral Sciences
David Geffen School of Medicine at UCLA
Do women with vasomotor symptoms have higher bone turnover than women without
vasomotor symptoms? – Year 19 (2009-2010)
Carolyn J. Crandall, MD, MS – [email protected]
Associate Professor of Medicine
David Geffen School of Medicine at UCLA
Regulation of beta cell proliferation and regeneration with aging – Year 19 (2009 – 2010)
Sangeeta Dhawan, PhD – [email protected]
Postdoctoral Fellow, Larry L. Hillblom Islet Research Center, UCLA
Anil Bhushan, PhD – [email protected]
Assistant Professor, Larry L. Hillblom Islet Research Center, UCLA
Implementation of a Geriatric Surgery Clinical Pathway to Increase Post-Operative
Function and Independence – Year 19 (2009 – 2010)
David Chen, MD – [email protected]
Assistant Clinical Professor of Surgery
David Geffen School of Medicine at UCLA
Probing the Role of Rare Gene Expression Outliers in Neurodegenerative Dementia – Year
19 (2009 – 2010)
Giovanni Coppola, MD – [email protected]
Assistant Professor of Neurology
David Geffen School of Medicine at UCLA
Investigation of a Novel Collagen Sponge Platform for Bone Formation and Regeneration –
Year 19 (2009 – 2010)
Maie St. John, MD, PhD – [email protected]
Assistant Professor of Surgery
David Geffen School of Medicine at UCLA
Inflammatory Markers, Daytime Sleeping and Functional Recovery among Older Adults in
Post-Acute Rehabilitation - Year 19 (2009 – 2010)
Jennifer Martin, PhD – [email protected]
Assistant Professor of Medicine
David Geffen School of Medicine at UCLA
III.
CAREER DEVELOPMENT AWARDS
David Walker, PhD (2009-2011) – [email protected]
Assistant Professor of Physiological Sciences
Title of Research: Genes that protect against oxidative stress and aging in Drosophila
Aging is characterized by a general decline in physiological function that leads to morbidity and
mortality. Specific causes of this decline are not known, although various lines of evidence
implicate oxidative stress as being a fundamental driving force behind this process. The
mitochondrial electron transport chain (ETC) is the principal source of reactive oxygen species
(ROS) within cells. Despite considerable medical interest, the molecular mechanisms that
regulate ROS-mediated pathogenesis remain poorly understood. The potential contribution of
Drosophila genetics to understanding mitochondrial dysfunction has been largely neglected. The
isolation of genetic modifiers of mitochondrial dysfunction in vivo may identify potential
therapeutic targets for a number of age-related diseases.
The goal of this project is to harness the powerful genetics of the fruit fly Drosophila to better
understand the damaging effects of ROS and to develop strategies to counteract the damage.
Previously, we reported the isolation and characterization of a fly mutant with a defect in subunit
b of mitochondrial respiratory complex II (sdhB). The complex II defect leads to elevated
oxidative stress and hallmarks of accelerated pathological and behavioral aging. The isolation
and characterization of this complex II mutant provides an excellent starting point for a
comprehensive analysis of the role of mitochondrial oxidants in modulating lifespan in
Drosophila. We will investigate the phenotypic, biochemical and physiological consequences of
respiratory complex II deficiency in different cells and tissues. To manipulate respiratory
complex II activity, we will use a combination of RNA interference (RNAi) and tissue-specific
transgenic rescue with the wild-type gene. Moreover, we have discovered that increased
expression of the sdhB gene can extend the lifespan of normal flies by up to 50%. Here, we
propose to examine the underlying physiological and biochemical mechanisms at play.
A major advantage of Drosophila as a model is the ability to conduct unbiased genetic modifier
screens for enhancers and suppressors of mutant phenotypes in vivo. The characterization of the
complex II mutant provides an excellent starting point for the initiation of modifier screens to
identify the molecular mediators of ROS-mediated pathogenesis. We will carry out genetic
screens to identify suppressors and enhancers of complex II deficiency.
During my postdoctoral training, I identified an additional five genes that protect against
oxidative stress and aging that await further characterization. At present, several of these genes
have no annotated functions. In each case, transgenic lines will be generated and the effects of
spatial and temporal manipulation of the gene on longevity will be examined. To do so, we will
use the latest molecular genetic tools available in Drosophila: in vivo RNAi under the control of
an inducible gene expression system.
Michael Yeh, MD (2009-2011) – [email protected]
Assistant Professor of Surgery
Title of Research: Primary hyperparathyroidism as a risk factor for cardiovascular disease in the
elderly
Primary hyperparathyroidism (PHPT) is a disease that disproportionately affects the elderly.
Existing data regarding the natural history of PHPT and outcomes of surgical management in the
elderly are limited. We will examine the utilization of parathyroid surgery and the potential
adverse health effects of primary hyperparathyroidism in this population, using two
complementary administrative databases. Cardiovascular disease will receive particular
attention, as prior epidemiologic studies have suggested an association between primary
hyperparathyroidism and premature death from cardiovascular causes.
These studies will examine the hypothesis that in elderly patients primary hyperparathyroidism is
an undertreated disease that contributes to excess cardiovascular morbidity and mortality, by
pursuing the following specific aims:
1) Compare the utilization of parathyroid surgery in elderly vs. non-elderly individuals,
while controlling for comorbidities and disease severity.
2) Evaluate the impact of PHPT on rates of hospitalization for cardiovascular diagnoses in
elderly individuals.
3) Examine the impact of PHPT on premature death from cardiovascular causes in elderly
individuals.
4) Evaluate the effect of surgical intervention on the clinical endpoints mentioned in aims #2
and #3.
Diana Tisnado, PhD (2008 – 2011*) – [email protected]
Associate Professor of Medicine
*Dr. Tisnado originally received her CDA in 2008, but shortly thereafter received a diversity
supplement from the NIA-funded RCMAR program at UCLA which replaced the first 2 years of
her CDA. OAIC support for her 3rd year will be completed on June 30, 2011.
Title of Research: An evaluation of lay navigators as an intervention to improve breast cancer
screening among Pacific Islanders
Approximately 60% of new breast cancer cases each year are in women 60 years or older, the
fastest growing segment of our population. Existing literature generally portrays older Asian
American and Pacific Islanders in aggregate as experiencing equal or better health than whites.
However, aggregating these data masks the high variability among sub-groups. Breast cancer is
the leading cancer site among Pacific Islander women, with high rates of late-stage diagnosis.
Pacific Islanders overall experience worse 5-year mortality rates than whites, and Samoans
experience worse 5-year mortality rates than all other ethnic groups. Late diagnosis appears to be
a significant determinant of these poor survival rates. Pacific Islanders experience screening rates
that are far below national recommendations, and that decrease with increasing age. Therefore,
there is great potential for targeted screening interventions to reduce cancer mortality in these
groups. Cultural beliefs, lack of knowledge, and distrust of Western healthcare are significant
barriers to cancer screening among Southeast Asian and Pacific Islanders.
Patient navigation services have been gaining attention as a promising intervention to address
barriers to healthcare experienced by underserved patients. However, little work has been
published describing evaluations of the effectiveness of patient navigators, particularly
community-based, lay navigators. The Orange County Asian and Pacific Islander Community
Alliance (OCAPICA) and Sora ParkTanjasiri have obtained a 5-year Centers for Disease Control
and Prevention (CDC) Center for Excellence in the Elimination of Disparities (CEED) grant to
improve cancer screening rates among Southeast Asians and Pacific Islanders in the U.S. and its
territories.
Dr. Tisnado works in collaboration with the OCAPICA CEED to examine the use of communitybased lay navigators as an intervention to assist older Pacific Islander women with access to
breast cancer screening services in Southern California.
UCLA OAIC CDA Awardees (Current Cycle 2006 – 2011)
Name
Current Status
FORMER AWARDEES
OAIC CDA Award/
Year of Award
Jennifer Martin, PhD
Assistant Research Professor, of
Medicine, David Geffen School of
Medicine at UCLA
2004-2007
Subsequent Grants, Career Development Awards
1.
UCLA Claude Pepper Older Americans Independence Center. (AG-10415). “The relationship
between sleep and inflammatory markers among older adults undergoing post-acute
rehabilitation.” Role on project: PI. September 2005- June 2006. Total direct costs: $20,000.
2. VA Health Services Research and Development. (IIR 04-321-2). “Non-pharmacological
interventions on sleep in post-acute rehabilitation.” Role on project: Co-Investigator (PI:
Cathy A. Alessi, MD). July 2006–June 2010. Total direct costs: $851,195.
3. UCLA Claude Pepper Older Americans Independence Center. (AG-10415). “Inflammatory
Markers, Daytime Sleeping and Functional Recovery among Older Adults in Post-Acute
Rehabilitation.” Role on project: PI. April 2010-June 2010. Total direct costs: $9,000.
4. National Institutes of Health, National Institute on Aging. (K23 AG028452). "Sleep-related
predictors of function and health among vulnerable older people." Role on project: PI.
July 2007- June 2011. Total direct costs: $375,000.
5. National Institutes of Health, National Institute on Aging. Clinical Research Loan repayment
Program (L30 AG032916). "Sleep and Health in Vulnerable Older People.” Role on project:
PI. July 2008-June 2011. Total award: $40,000.
6. VA Health Services Research and Development. (IIR 08-295-1). "Implementing Sleep
Interventions for Older Veterans." Role on project: Co- investigator (PI: Cathy A. Alessi,
MD). July 2009-June 2013. Total direct costs: $899,900.
7. VA Rehabilitation Research and Development. (1RX000135-01). "Treating sleep problems in
VA Adult Day Health Care." Role on project: PI. January 2010-December 2012. Total direct
costs: $595,800.
8. National Institutes of Health, National Institute on Aging. (1R01AG034588-01). "Subjective
Social Isolation and Sleep Disturbances: Inflammatory Mechanisms in Aging." Role on
Project: Co-I. September 2009–June 2014. Total direct costs: $1,306,735.
9. VA Health Services Research and Development. (PPO 09-282-1). "Women Veterans with
Insomnia: Characteristics and Treatment Preferences." Role on project: PI. Funding period:
TBA. Total direct costs: $100,000.
10. VA Health Services Research and Development. (PPO 09-239-1). “Treatment of Insomnia in
Older Veterans: Identifying Obstacles to Best Practices.” Role on project: Co-investigator (PI:
Cathy Alessi). June 2010-May 2011. Total direct costs: $100,000
UCLA OAIC CDA Awardees (Current Cycle 2006 – 2011)
Name
Current Status
Tara Gruenewald, PhD
Assistant Professor of Medicine
David Geffen School of Medicine
at UCLA
OAIC CDA Award/
Year of Award
2005-2007
Subsequent Grants, Career Development Awards
1.
2.
3.
4.
5.
Kathrin Maedler, PhD
Director, Islet Research Laboratory,
University of Breman Germany
2005-2007
1.
2.
3.
4.
5.
6.
7.
8.
National Institutes of Health, National Institute on Aging. (K01 AG028582-01A).
“Perceptions of Social Value/Usefulness as Predictors of Health in Older Adults.” Role on
Project: PI. July 2007-June 2012. Total direct costs: $619,106.
National Institutes of Health, National Institute on Aging. (K01 AG028582-03S1).
“Experience Corps Volunteer Experiences Survey.” Role on project: PI. September 2009August 2011. Total direct costs: $100,000.
National Institutes of Health, National Institute on Aging. (P01 AG027735-01). Subcontract
from Johns Hopkins University. “Improving Health of Older Populations through
Generativity.” Role on project: Co-investigator (PI: Fried). December 2006-November 2011.
Total direct costs: $15,000.
UCLA Faculty Research Grant. “Development of a Measure of Perceived Usefulness to
Others for Use in Older Adults.” Role on project: PI. July 2006-June 2007. TDC: $3,000.
National Institutes of Health, National Institute on Aging. (P30 AG017265). “USC/UCLA
Center for Biodemography.” Role on project: Co-investigator (PI: Crimmins). October 2005June 2006. Total direct costs: $20,000.
Juvenile Diabetes Research Foundation. JDRF Regeneration Program. “Beta Cell
Regeneration in humans, a therapy for type 1 diabetes?” Role on project: Coinvestigator/Core B. August 2005-July 2007. Total direct costs: $1,122,136.
UCLA 2006-07 COR FGP Faculty Research Award. “Why do pancreatic beta cells undergo
cell death in diabetes?” Role on project: PI. August 2006-July 2007. Total direct costs:
$6,000.
Stein Oppenheimer Foundation. “Mechanisms and modulation of TOSO, a signal for
proliferation, in pancreatic B-Cells.” Role on project: PI. July 2006-June 2007. Total direct
costs: $20,000.
Larry L. Hillblom Foundation. “Inflammatory mechanisms in Type 2 Diabetes: the role of IP10 and SOCS-3 in glucose induced B-Cell apoptosis.” Role on project: PI. June 2005-May
2008. Total direct costs: $210,000.
American Diabetes Association Junior Faculty Award. (7-06-JF-41). “The potent role of IL1Ra to improve beta cell survival in obesity and diabetes.” Role on project: PI. August 2006July 2009. Total direct costs: $360,000.
National Institute of Health, National Institute on Aging. (NIH-RFA-DK-05-011). “Animal
models of diabetic complications consortium.” Role on project: Co-investigator. September
2006-August 2011. Total direct costs: $1,250,000.
German Research Foundation, Emmy Noether Program. “Chemokines in Diabetes.” Role on
project: PI. Funding period: 2008-2009. Total direct costs: Unknown.
European Foundation for the Study of Diabetes. EFSD-MSD basic program. “TCF7L2 in
T2DM.” Role on project: PI. Funding period: July 2008-June 2010. Total direct costs:
100,000 EURO ($139,176.68 USD).
UCLA OAIC CDA Awardees (Current Cycle 2006 – 2011)
Name
Current Status
David A. Ganz, MD, PhD
Assistant Professor of
Medicine/Geriatrics, David Geffen
School of Medicine at UCLA
OAIC CDA Award/
Year of Award
2007-2008
Subsequent Grants, Career Development Awards
VA Health Services Research and Development. (VA CD2 08-012-1). “CDA: Improving
Implementation of Fall Prevention Programs in Older Veterans.” August 2008-July 2013.
Total direct costs: $1,050,235.
2. VA/Robert Wood Johnson Foundation. VA Physician Faculty Scholars Program. “Improving
Implementation of Fall Prevention Programs in Older Veterans.” July 2009-June 2012. Total
direct costs: In-kind support.
3. VA Quality Enhancement Research Initiative. (VA RRP 09-202). “Improving Quality of
Primary Care for Fall Prevention in Older Veterans.” April 2010-March 2011. Total direct
costs: $83,365.
4. Hartford/UCLA Geriatrics Center of Excellence. “Improving Implementation of Fall
Prevention Programs in Older Veterans.” July 2010-June 2011. Total direct costs: $28,435.
5. VA Health Services Research and Development. (VA LIP 65-127). “Evaluation of a primary
care quality improvement program to prevent falls.” August 2010-July 2011. Total direct
costs: $20,196.
6. The California Endowment. (UCLA 2007-2075). “Blue Sky Initiative, Phase III.” Role on
project: Co-investigator (PI: Halfon). February 2008-June 2010. Total direct costs:
$1,450,000.
7. RAND Internal Research and Development. (RAND RSU08HE). “Linking quality measures
with electronic health records.” Role on project: Co-investigator (PI: Bell). October 2007September 2008. Total direct costs: $177,322.
8. United HealthCare. (RAND HQ046). “Evercare project.” Role on project: Co-investigator
(PI: Wenger). November 2007-March 2010. Total direct costs: $1,380,000.
9. Atlantic Philanthropies. (RAND HE962). “ACP Geriatric Care Improvement Grant
Supplement, subcontract to RAND.” Role on project: Co-investigator (PI’s: Reuben/Wenger).
July 2008-January 2009. Total direct costs: $249,430.
10. VA Quality enhancement Research Initiative. (VA RRP 08-382). “Rapid Response Project:
Survey of VA Clinicians’ Falls Prevention and Assessment Practices.” Role on project: Coinvestigator (PI: Kramer). October 2008-March 2009. Total direct costs: $53,260.
11. VA Health Services Research and Development Nursing Research Institute. (VA NRI 08370). “Pilot study: Preparing for a Parkinson’s Disease Care Management QI Trial.” Role on
project: Co-investigator (PI: Connor). February 2009-July 2010. Total direct costs: $99,277.
12. The SCAN Foundation. (VA PROMISE #0004). “SCAN Memory Program Evaluation
Study.” Role on project: Co-investigator (PI: Chodosh). June 2009-May 2012. Total direct
costs: $725,530.
1.
UCLA OAIC CDA Awardees (Current Cycle 2006 – 2011)
Name
Current Status
Veena Ranganath, MD
Assistant Professor of Medicine,
David Geffen School of Medicine
at UCLA
OAIC CDA Award/
Year of Award
2006-2009
Subsequent Grants, Career Development Awards
1.
2.
3.
4.
5.
6.
7.
8.
O. Kenrik Duru, MD
Assistant Professor of Medicine,
David Geffen School of Medicine
at UCLA
2008-2009
1.
2.
3.
4.
NIH-mentored Patient-Oriented Research CDA. (K23 AR057818-01A1). “Biomarkers for
Early Therapeutic Response in Older RA Patients.” Role on project: PI. July 2010-June 2015.
Total direct costs: $121,230/yr.
ACR/REF/AF Career Development Bridge Funding Award. Provides funding until PI obtains
NIH K23 grant. Role on project: PI. August 2009. Total direct costs: $75,000.
Iris Cantor-UCLA Women’s Health Center Pilot Award. “Prospective Study of Aromatase
Inhibitor-associated Musculoskeletal Symptoms in Non-Metastatic, Post menopausal Breast
Cancer Patients.” Role on project: PI. August 2009. Total direct costs: $45,000.
OAIC Research Funding Grant. “Potential Markers of Response to Therapy in RA Patients: a
pilot study.” Role on project: PI. September 2008. Total direct costs: $20,000.
UCLA GCRC Grant. “Potential Markers of Response to Therapy in RA Patients: A Pilot
Study.” Role on project: PI. December 2008. Total direct costs: $20,000.
ACR/RFA. “Guidelines for the Prevention and Management of Glucocorticoid-induced
Osteoporosis.” Role on project: Co-investigator (PI: Grossman). 2008. Total direct costs:
$60,000.
ACR/REF Within Our Reach Award. “Joint MRI to Validate Clinical Remission Criteria in
Early RA.” Role on project: Co-investigator (PI: Paulus). 2007-2009. Total direct costs:
$200,000/yr.
ACR/REF Clinical Investigator Fellowship Award. “Genetic Factors in Older Onset
rheumatoid arthritis.” Role on project: PI. 2007-2009. Total direct costs: $90,000/yr.
Robert Wood Johnson Foundation. Harold Amos Medical Faculty Development Award.
“Mail-order Pharmacy Use and Adherence to Diabetes-related Medications.” Role on project:
PI. January 2009-December 2012.
National Institutes of Health, National Institute on Aging. (K08 AG033630-01A1). “Mentored
Clinical Scientist Research CDA.” Role on project: PI. September 2009-August 2014.
National Institutes of Health, NIDDK. (1R03DK089122-01). “The Coverage Gap and
Clinical Outcomes in a Medicate Advantage Part D Population.” Role on project: PI. July
2010-June 2013.
Centers for Disease Control and Prevention. (1U58DP002722-01). “The Diabetes Health
Plan: a System Level Intervention to Prevent and Treat Diabetes.” Role on project: Coinvestigator (PI: Mangione). September 2010-September 2015.
UCLA OAIC CDA Awardees (Current Cycle 2006 – 2011)
Name
Current Status
CURRENT AWARDEES
OAIC CDA Award/
Year of Award
Diana Tisnado, PhD
Adjunct Asst Prof
Medicine/GIM/HSR
7/08-12/08 and
7/10-present
Subsequent Grants, Career Development Awards
1.
2.
3.
David Walker, PhD
Asst Prof
Physiological Sciences
7/09-present
Michael Yeh, MD
Asst. Prof of Surgery and Medicine
7/09 - present
1.
2.
Drew/UCLA/RAND Project EXPORT. (2P20MD000182-06). “Fatalism and Religiosity:
Concepts Addressing Preventive Health Behaviors Among Latinas.” Role on project: PI of
pilot (PI: Norris/Shapiro). July 2010-June 2011. Total direct costs: $20,000.
UCLA Center for Health Improvement of Minority Elderly/ NIA Resource Centers for
Minority Aging Research. (3P30 AG021684:07S2). “Lay Navigators as an Intervention to
Improve Breast Cancer Services among Pacific Islanders (Supplement).” Role on project: PI
of supplement (PI: Mangione). September 2008-June 2010. Total direct costs: $94,966.
California Breast Cancer Research Program Community Research Collaborative. (14AB2000). “Latina Breast Cancer Survivors: Our Experience.” Role on project: PI. July 2008March 2010. Total direct costs: $150,000.
National Institutes of Health, National Institute on Aging. (R01). “Increased respiratory chain
activity and animal aging.” Role on project: PI. July 2010-June 2015.
UCLA Claude Pepper Older Americans Independence Center. Pilot Grant. “Examining
genome-wide alterations in gene expression in long-lived Drosophila mutants.” Role in
project: PI of pilot (PI: Reuben). July 2010-June 2011.
Pending:
1.
2.
NIA GEMSSTAR R03: "Long term impact of primary hyperparathyroidism in the elderly"” 07/11 - 06/13
Jahnigen Career Development Award/ GEMSSTAR Program: "Long term impact of primary
hyperparathyroidism in the elderly"” - 07/11 - 06/13
University of California, Los Angeles
David Geffen School of Medicine at UCLA
Claude D. Pepper Older Americans Independence Center
2010/2011 SCIENTIFIC AWARDS
Carol Mangione, MD
•
•
•
•
2010 Will Solimene Award for Excellence in Medical Communication, American
Medical Writers Association, New England Chapter, "Living with Diabetes:
Making Lifestyle Changes to Last a Lifetime", content editor
2010 Will Solimene Award for Excellence in Medical Communication, American
Medical Writers Association, New England Chapter, "Growing Older, Staying
Well", content editor
2010 Bronze Medal, National Health Information Awards, Patient Information
Category, "Growing Older, Staying Well", content editor
2010 Platinum EMPixx Award, Corporate Videos and Films Category, "Growing
Older, Staying Well", content editor
Alison Moore, MD, MPH
•
•
Dorothy Dillon Eweson Lecturer on Advances in Aging Research, awarded by the
American Federation for Aging Research (2011)
Invited Professor, Division of Geriatric and Palliative Medicine, University of Texas
Health Science Center at Houston (2011)
Mary-Frances O’Connor, PhD
•
•
NSF/University of Arizona ADVANCE Junior Scientist Award (2010)
Advanced Research Institute in Geriatric Mental Health Scholar (2011)
Maie St. John, MD, PhD
•
•
•
•
•
•
•
UCLA Health System Humanism Award – one of the top 10 most humanistic
physicians at UCLA, 2011
Head and Neck Triological Society – Honor Award for Triological Society Thesis
2011
Los Angeles “Superdoctor,” Otolaryngology, 2011, Los Angeles Magazine
Award for the best clinical paper at the ACS International Conference, Santa
Barbara, CA, 2011
Award for the best paper at the AHNS International Conference, Chicago, Ill,
2011
Award for the best paper at the Triological Conference, Chicago, Ill, 2011
Award for the best paper at the AHNS International Conference, Las Vegas, NV,
2010
Benjamin Sun, MD
•
Society for Academic Emergency Medicine Young Investigator Award, 2010
Derjung Mimi Tarn, MD, PhD
•
2010 California Academy of Family Physicians (CAFP) Researcher of the Year
Michael Yeh, MD
•
2010 UCLA Alpha Omega Faculty Inductee
University of California, Los Angeles
David Geffen School of Medicine at UCLA
Claude D. Pepper Older Americans Independence Center
MINORITY RESEARCH AT UCLA PEPPER CENTER
2010/2011
General Brief Description of Minority Activities:
RCMAR Initiative:
The UCLA OAIC provides ongoing operational assistance to the new UCLA Resource Center
for Minority Aging Research (RCMAR), one of six centers funded for the 2007-2012 cycle of
this NIH initiative. Carol M. Mangione, MD, MSPH, director of the UCLA OAIC Recruitment
Core, is also the principal investigator of the UCLA RCMAR program, called the Center for
Health Improvement for Minority Elders (CHIME).
CHIME is a collaborative research and mentoring program with faculty at UCLA and Charles R.
Drew University that addresses health disparities for African American and Latino elders
through training and mentorship of minority faculty. CHIME also provides the research
infrastructure needed to improve the health of minority elders through participatory research
within local communities. The center is active in the recruitment, retention, and promotion of
minority junior faculty through mentorship and support of research efforts on the health of
minority elders.
In addition, Janet C. Frank, DrPH, MSG, administrator of the UCLA OAIC Leadership Core, is
director of the RCMAR National Coordinating Center (CC) for the 2007-2012 funding cycle.
The CC provides logistical support to the six RCMAR centers and leads the effort to ensure their
research is disseminated to the larger research and health professional communities, public
policy makers, and consumers. The CC also serves as the national clearinghouse for
measurement tools, instruments, and other resources developed by RCMAR investigators for use
by health researchers and other professionals. The RCMAR CC plans to include Pepper Centers,
Alzheimer’s Disease Centers, Roybal Centers and others in future activities that are focused on
minority faculty development and minority aging research.
Minority Trainees:
O. Kenrik Duru, MD: Dr. Duru is an assistant professor at UCLA. Dr. Duru received a one-year
OAIC pilot grant, “Identifying predictors of transitions between physical activity and inactivity
among community-dwelling older persons.” His one-year pilot award started in July 2007.
Additionally, he was awarded a 3-year OAIC Career Development Award, “Developing “Sisters
in Motion 2 – Evaluation and Refinement of an Existing Physical Activity Intervention for Older
African American Women.”
Carolyn Mendez-Luck, PhD: Dr. Mendez-Luck is an adjunct assistant professor in the
Department of Community Health Sciences in the UCLA School of Public Health. Her research
interests are: informal caregiving, health and aging of Latino populations, health insurance
coverage and access to care for racial/ethnic minorities.
Didra Brown Taylor, PhD: Dr. Brown-Taylor is a visiting researcher in the Integrated Substance
Abuse Program in the Department of Psychiatry. Her research interests are alcohol abuse issues
among African-Americans.
Marie Fongwa, RN, MPH, PhD: Dr. Fongwa is an assistant professor at the UCLA School of
Nursing. Her research has focused on quality of care with special interests in patient satisfaction
and culture.
Arleen F. Brown, MD: Dr. Brown is a general internist and health services researcher with
expertise in quality of care for older adults and minorities with diabetes. Dr. Brown’s work has
focused on health care system, social, and individual level determinants of health for persons
with diabetes.
Michael Rodriguez, MD, MPH: Dr. Rodriguez is an associate professor in the Department of
Family Medicine at UCLA. Dr. Rodriguez conducts research, works with direct service and
advocacy organizations, and helps inform policy on violence prevention and the healthcare needs
of vulnerable populations. He is currently a co-director of the UCLA OAIC Recruitment Core.
Marta Epeldegui is a doctoral student in Microbiology, Immunology and Molecular Genetics,
working on the pathogenesis of B cell lymphoma under the supervision of Otoniel MartinezMaza. Her research has focused on the role of activation-induced cytidine deaminase (AID) in
non-Hodgkin’s lymphoma. In a study recently published in Molecular Immunology, Ms.
Epeldegui found that Epstein-Barr virus (EBV) exposed B cells rapidly express AID and that this
results in oncogene mutation.
Diana Tisnado, PhD. is an adjunct assistant professor in the Division of General Internal
Medicine at UCLA. Dr. Tisnado received an NIA Diversity Supplement Award and is currently
an OAIC CDA recipient. She is working in collaboration with the Orange County Asian and
Pacific Islander Community Alliance (OCAPICA) Center for Excellence in Eliminating
Disparities to examine the use of community-based lay navigators as an intervention to assist
older Pacific Islander women with access to breast cancer screening in Southern California.
Minority-Related Research Projects:
Alison A. Moore, MD, MPH, UCLA OAIC Research Career Development Core (RCDC) codirector, is conducting research among older Latinos to determine whether a screening and
advice intervention to reduce risky drinking she had previously developed is relevant for this
population and to make changes to the intervention if not.
Publications (2010-2011)
1.
2.
3.
4.
Duru OK, Sarkisian CA, Leng M, Mangione CM. Sisters in Motion: A Randomized
Controlled Trial of a Faith-Based Physical Activity Intervention. Journal of the American
Geriatrics Society 2010 Oct;58(10):183-9
Tisnado DM, Sablan-Santos L, Quenga J, Guevara L, Quitugua L, Castro K, Aromin J,
Tran J. Evaluating community-based navigation as an intervention to improve access to
breast cancer services among the Chamorro: Community and academic engagement for a
community partnered research approach. Californian Journal of Health Promotion. 2010:
8(SE): 39-51.
Vaivao DES, Lutu G, Hannemann M, Tulua-Tata A, Tisnado DM. Assessing the
effectiveness of educational workshops for breast cancer prevention in Samoan women in
Southern California. Californian Journal of Health Promotion. 2010; 8(SE): 1-10.
Walker KO, Steers WN, Liang L, Morales LS, Jones L, Brown AF. The vulnerability of
older minorities without insurance for delays in care and preventive service use in south Los
Angeles.” J Am Ger Soc 2010 Dec;58(12):2416-22
University of Florida
Claude D. Pepper Older Americans Independence Center
Marco Pahor, M.D.
Principal Investigator
Department of Aging and Geriatrics
College of Medicine
University of Florida
PO Box 100107
Gainesville, FL 32610
Phone: 352-265-7227 Fax: 352-265-7228
Email: [email protected]
I.
Lauren Crump, M.P.H.
Project Director
Department of Aging and Geriatrics
College of Medicine
University of Florida
PO Box 100107
Gainesville, FL 32610
Phone: 352-265-7227 Fax: 352-265-7228
Email: [email protected]
CENTER DESCRIPTON
The mission of the UF OAIC is (1) to assess the risk factors and better understand the biological
mechanisms of physical disability in older adults, (2) to develop and test effective prevention and
rehabilitation therapies, and (3) to educate and train new investigators in research on aging and disability,
while developing their leadership qualities and roles. Our overall strategy is to attract studies and investigators
from diverse behavioral, clinical and basic science disciplines towards research on aging focusing on a
common theme. This, in turn will allow us to accomplish our mission. Our research theme is “Sarcopenia,
prevention and rehabilitation of disability” examined from interdisciplinary perspectives translating across
the entire spectrum of biomedical investigation, including molecular biology, animal studies, clinical research,
behavioral and social sciences, and epidemiology. We have assembled an outstanding interdisciplinary team
of investigators and we have successfully developed special areas of expertise and competencies, which are
represented in the integrated cores that support our research and training program. The following integrated
structure will allow us to achieve the OAIC mission:
The Leadership and Administrative Core (LAC, Leader: Marco Pahor, MD) is responsible for
scientific leadership, strategic planning, organization, administrative operations, review, evaluation, tracking
and monitoring of the OAIC research and training program. It is supported by the OAIC Executive Committee,
the Independent Review Advisory Panel, and the External Advisory Committee.
The Research Career Development Core (RCDC, Leader: Elena Andresen, PhD; Co-Leader
Christiaan Leeuwenburgh, PhD) seeks to promote and augment the development of future research leaders in
the area of focus of this OAIC application, i.e., “Sarcopenia, prevention and rehabilitation of disability”. The
core emphasizes development of multidisciplinary skills for translating across traditional boundaries of
scientific disciplines. Resources of this core are being integrated with other sources for career support, such as
institutional support, the NIH and other source career development and research awards. It employs structured
education and a formal mentoring process for Junior Scholars, who are stringently selected to join the core.
The Pilot / Exploratory Studies Core (P/EC, Leader; Christy Carter, PhD; Susan Nayfield, MD)
supports research to acquire information needed to select or design future clinical and preclinical research
studies in the OAIC areas of focus.
The Clinical Research Core (RC 1, Leader: Susan Nayfield, MD) supports research in human
subjects, including controlled trials, observational studies, pilot studies, and research development studies. The
goals of the RC1 are (a) to select and utilize optimal measures for clinical trials and observational studies, (b)
to understand the physiological and biomechanical mechanisms contributing to changes in walking, (c) in
collaboration with the Biostatistics, Data Management Core to conduct secondary analyses of randomized
clinical trials or observational studies and (d) to develop behavioral interventions to improve physical function
and quality of life of older individuals.
The Preclinical Research Core (RC 2, Leader: Philip Scarpace, PhD, Co-Leader: Christy Carter, PhD)
supports both mechanistic and intervention studies in animals models in the OAIC area of focus. Results and
hypotheses tested in this Core and in the Genomics and Biomarkers Core are translated and applied to clinical
studies by the Clinical Research Core. Concepts on disability that are developed in the Clinical Research and
the Genomics and Biomarkers Cores are applied in this Core.
The Biostatistics and Data Management Core (RC 3, Leader: Michael Daniels) supports all research
activities in the planning, implementation and analytical phases, and develops novel analytical methodologies.
RC 3 is responsible for data management and quality control. This Core devises analytical strategies, which
will take advantage of the uniform measures of physical function and biomarkers assessed across all OAIC
studies.
The Recruitment Core (RC 4, Leader: Michael Marsiske, PhD, Co-Leader: Susan Nayfield, MD)
develops novel recruitment, retention and adherence strategies (with particular focus on minorities), supports
recruitment of participants and promotes adherence in OAIC studies.
The Genomics and Biomarkers Core (RC 5, Leader: Christiaan Leeuwenburgh, PhD) conducts
studies on biomarkers and genetics of sarcopenia, physical function and disability. The core primarily focused
on mitochondrial energy utilization, inflammation, oxidative stress, and apoptosis.
We plan to attract investigators and independently funded studies in the area of research on aging that are
specifically targeted towards the main theme of “Sarcopenia, prevention and rehabilitation of disability”. We
support expertise, resources, and measures, which address this theme. The UF OAIC focuses primarily on, but
is not limited to, mechanistic and intervention studies in humans and small animals. Our research program
maximizes the translation of information, knowledge, hypotheses, and resources across basic, clinical,
behavioral and social sciences. This approach helps to further develop and strengthen our environment for
educating new investigators and future leaders in research on aging. A major strength of the UF OAIC consists
of the concerted action of a broad range of interdisciplinary cores and projects that address one common
research theme, to be pursued through the whole spectrum of biomedical investigation.
II. RESEARCH, RESOURCES AND ACTIVITIES
A. Cores
Leadership and Administrative Core (LAC)
Leader: Marco Pahor, M.D.
Phone: 352-265-7227
Fax: 352-265-7228
Email: [email protected]
The Leadership and Administrative Core (LAC) is responsible for strategic planning, organization,
administrative operations and evaluation of the OAIC Research and Training program. A special effort
is being devoted to ensure the coherence of the Center and maintaining an interdisciplinary focus on
the common research theme, which is “sarcopenia, prevention and rehabilitation of disability”. The
LAC tasks are being achieved by the Core Leader and three committees: the Executive Committee, the
Independent Review Advisory Panel and the External Advisory Committee. The specific functions of
the Leadership Core are:
- To provide overall scientific leadership and direction for the OAIC research and training program.
- To render administrative and budgetary support for the program
- To coordinate the functions of the OAIC cores and projects in order to facilitate communication
and foster translation between basic and clinical research and ensure access of investigators to core
resources.
- To assure the coordination of OAIC resources and functions with other research and training grants
and institutional resources
- To communicate with other OAICs and the NIA, and to foster collaborations with other OAICs
- To facilitate compliance with guidelines and regulations regarding fiscal policy, human subjects,
and animal care and use. The LAC has implemented procedures to ensure that all OAIC supported
studies comply with the HIPAA regulations. The Safety Committee has been named and meets
-
-
semiannually by conference call. The Safety Committee members are the following:
- Steve Kritchevsky, PhD. Expertise in Clinical trials, observational studies, disability
- John Meuleman, MD. Expertise in geriatric medicine
- Jing Chen, PhD. Expertise in biostatistics
To set productivity benchmarks and monitor progress of individual projects and progress of junior
investigators (this aim is shared with the RCDC), and deal with inadequate progress
To promote quality, productivity and efficiency (timeliness) in all OAIC activities
To arrange the annual meeting of the OAIC External Advisory Committee. The annual meeting of
the OAIC External Advisory Committee took place in January 2011. The invited External Advisory
Committee Members are Dr. George Taffett, Baylor University, Dr. Doug Miller, Indiana
University, Dr. Jeremy Walston, Johns Hopkins University, and Dr. Russ Tracy, University of
Vermont.
To maintain the OAIC web-based tracking and monitoring system to facilitate communication
To promote the use of uniform assessment batteries in OAIC supported clinical research studies to
optimize the use of OAIC resources
To maintain the OAIC website and publish the OAIC newsletter
Research Career Development Core (RCDC)
Leader: Elena Andresen, PhD
Phone: 352-273-5359
Fax: 352-273-5365 Email: [email protected]
Co-Leader: Christiaan Leeuwenburgh, Ph.D.
Phone: 352-273-5913
Fax: 352-273-5920 Email: [email protected]
The RCDC promotes the development of independent investigators in interdisciplinary research on
aging relevant to the independence of older Americans. This core emphasizes the development of
leadership skills for translating basic findings into clinical research and clinical findings into basic
research. The RCDC supports the research training of OAIC Junior Scholars who are trainees that span
the spectrum from beginning trainees who are not yet funded with an external career development
award or independent R01 type grant or its equivalent to advanced trainees who already have competed
successfully for career development or grants that provide substantial salary support. Currently, the
RCDC supports 7 Junior Scholars; 2 women, 5 men, from 2 colleges Medicine, Public Health and
Health Professions).
Under the direction of the RCDC Core leaders, each Junior Scholar has assembled a mentoring
committee with one primary mentor, and 2-4 secondary mentors who have formally met to discuss and
strategically plan their research agenda, training and development activities and trajectory for
independent funding. The mentorship model is based on the National Academy of Sciences, "Advisory,
Teacher, Role Model, Friend" model. One of the secondary mentors is not directly involved in the
mentee's research or clinical training. Mentors are chosen from a pool of basic, translational, social,
behavioral, epidemiological and clinical mentors, and matched to each Scholar in order to optimize
"translational thinking". Thus, the RCDC strives to identify mentors who can bridge basic and clinical
concepts. The RCDC provides the infrastructure support for each Scholar to acquire skills and
mentoring via a structured mentorship program that fosters basic and clinical sciences approaches
directly linked to other Cores of the OAIC. Scholars have regular meetings with their primary mentors
and quarterly meetings with their full mentoring team to assess their progress in relation to their
benchmarks, provide feedback, and career advice with formal progress reports.
In addition to their individualized training and educational plans, the RCDC in conjunction with its
academic partners in the UF Institute on Aging, Department of Aging and Geriatrics, VA Geriatric
Research Education and Clinical Center, VA Rehabilitation and Outcomes Center, and VA Brain
Rehabilitation Research Center provides ongoing seminars and educational activities. These formal
activities include a weekly one-hour interdisciplinary Aging and Rehabilitation Research Seminar, a
one-hour monthly research in progress meeting, a regular monthly “Scholars’ Roundtable, and a onehour weekly clinical geriatrics seminar. Campus-wide, grant writing courses are available to each
Scholar. Interaction with the biostatistical, pilot, and recruitment core is provided in the planning and
execution stages of their projects, and on an as-needed basis.
Currently, the RCDC supports 7 Junior Scholars; 2 women, 5 men, from distinct disciplines that
include, physiology, exercise science, basic laboratory science, and health psychology. Our current
Scholars are the following individuals. Thomas Buford, PhD, Lecturer, Department of Aging and
Geriatric Research, is investigating muscle regeneration and satellite cells. This study is in progress.
Andrew Judge, PhD, Assistant Professor, Department of Physical Therapy, is examining basic muscle
biology and plasticity. This study is in progress. Todd Manini, PhD, Assistant Professor, Department
of Aging and Geriatric Research, is an exercise physiologist who is studying the acute responses to
blood flow-restricted exercise in older adults. Dr Manini’s study is also underway and he has enrolled
24 of 25 patients to date, 22 of which are completed. Dr. Joe Nocera, PhD, is a VA Career Development
Awardee Research Scientist at the Malcom Randall VAMC as part of the BRRC. Dr. Nocera’s research
focuses on elucidating the impact of cognitive impairment on mobility disability, specifically gait and
postural control, in older adults with Parkinson’s disease. His research also indentifies behavioral
intervention as a means to improve/limit cognitive impairment and mobility disability. His long-term
research ambitions are to identify novel interventions that can limit and/or improve both the motor and
non-motor consequences on aging and neurological disease. His RCDC project is based on his VA
CDA “Aerobic exercise to improve executive language function in older adults.” Dr. David Clark,
ScD, is a Research Health Science Specialist with the Brain Rehabilitation Research Center at the
Malcom Randall VA Medical Center. His primary research interests involve elucidating the
neuromuscular and biomechanical impairments underlying mobility deficits in older adults and persons
post-stroke. His current OAIC research project is entitled “Locomotor reserve: a novel approach for
detecting mobility deficits with aging”, and aims to improve the early detection of emerging mobility
deficits in older adults, with particular emphasis on neuromuscular factors. Kevin Vincent, MD,
Assistant Professor in Orthopedics is a clinical studying osteoarthritis and eccentric exercise intervent.
Stephanie Woghlemuth, PhD, Assistant Professor, Department of Animal Sciences, is a zoologist in
stress physiology who is examining autophagy and sarcopenia in a transgenic mouse model. In her
project, she has found that the heterozygous transgenic mutator mice have a high mtDNA mutational
load, but they did not display the premature aging phenotype. This work has led her to an in-depth
investigation of autophagy, mitochondrial function and organ function of heart and skeletal muscle that
is ongoing. Jinze Xu, PhD, Post-Doctoral Associate, Department of Aging and Geriatric Research, is
studying iron homeostasis and mitochondrial dysfunction. This research is in progress. Dr. Xu has
transitioned from a funded post-doctoral fellowship to a supported Pepper Scholar. Zvinka Zlator,
Graduate Assistant, Department of Clinical and Health Psychology, is studying cognitive aging and this
research is ongoing. A Minority Supplement supports Ms. Zlator’s doctoral training. Each Scholar has
assembled their mentoring committee, formally met and agreed upon their career goals and research
benchmarks for their first year, and for the upcoming second year investigator meetings. Mentor
meetings have been held at least every six months.
Table 5. Junior Scholars supported by the OAIC 2007-2010
Stephen Anton, PhD (Aging, Psychology) (June 2007 – ongoing) Mentor, Michael Perri, PhD (Public Health &
Health Professions)
Papers Published/in Press: 33
Papers Submitted: 3
Grants Awarded
1. Dose-response effects of weight loss on systemic Levels of inflammation and oxidative stress, OAIC Pilot,
completed.
2. Dose response effects of weight loss on oxidative stress and inflammation, Anton PI, AHA, $149,825.
3. Investigations of botanicals on food intake, satiety, weight loss & oxidative stress, Anton PI, NIH K23,
$631,892.
4. Resveratrol supplementation and memory dysfunction in older adults, McKnight Brain Research Foundation
Dual PI with Manini, Brain Research Foundation, $100,000, completed.
5. Resveratrol supplementation for improved performance in the elderly: the RIPE trial, Anton PI, Thomas Maren
Jr Investigators Award, $40,000.
6. Reversal of age-related obesity by an unexpected synergy between leptin and wheel running, Shapiro PI,
OAIC pilot, completed.
7. The testosterone trial, Snyder PI, Pahor Local PI, Anton CoI, NIH U01AG030644, $2,217,324.
8. Rural lifestyle intervention treatment effectiveness trial (Rural LITE) minority suppl., Perri PI, NIH
R18HL087800, $293,000.
Grants Pending
1. Effects of naturally sourced lipid and chromium on glucose response, Lipid Nutrition, Anton PI, $177,229.
2. The papaya study, Anton PI, Osato Research Institute, Japan, $112,000.
3. Comparison of health approaches for improving mobility and physical performance in seniors (CHAMPS), NIH
K22MD006143, $4,428,988.
Grants Submitted, not Awarded
1. Synergistic effect of leptin and wheel running, University of Florida Institute on Aging
2. Effects of chewing gum on food intake, satiety, and body weight, Anton PI, Wrigley Science Institute, $25,000.
3. Effects of weight loss on novel cardiovascular risk factors, Anton PI, AHA, $110,000.
4. REACH-Reaching elder adults to improve access to cost effective healthcare, Anton PI, USDA, $350,000.
5. TOURS weight loss maintenance study, Anton PI, NAASO Obesity Society, $25,000.
6. Resveratrol for improved performance in the elderly: the RIPE trial, Anton PI, Brookdale Foundation,
$100,000.
Formal Courses Taken/Degrees Achieved
Introduction to Clinical/Translational Research Course (GMS 7093) July 21 – August 1, 2008
Miho Bautista, MD (Aging and VA GRECC) (April 2007 – July 2009) Mentor, Ronald Shorr, MD (Aging)
Degrees Achieved: Masters of Science (MS) in Clinical Investigation, August 2008 with the UF College of
Medicine via NIH K-30 award
Papers Published: 3
Papers Submitted: 1
Grants Completed:
1. Advanced postgraduate program in clinical investigation fellowship faculty research award. University of
Florida College of Medicine. 1/1- 12/31 2008
Thomas Buford, PhD (Aging) (June 2009 - ongoing) Mentor, Christiaan Leeuwenburgh, PhD (Aging)
Papers Published/in Press: 8
Papers Submitted: 1
Grants Awarded
1.Role of skeletal muscle blood flow in regeneration and sarcopenia (CTSI), Buford PI, University of Florida,
$164,000
2.Graded Vascular Occlusion, Buford PI, American College of Sports Medicine, $10,000
3.Muscle regeneration and sarcopenia, Buford, PI, Merck, $79,000
Andrew Judge, PhD (Kinesiology) (July 2008 – ongoing) Mentor, Lucia Notterpek, PhD (Neurosciences)
Papers Published/in Press: 8
Papers Submitted: 4
Grants Awarded
1. Cytokine-induced muscle atrophy following exercise claudication, Judge PI, James and Esther King
Biomedical Research Program, $169,063.
2. Heat shock proteins and disuse muscle atrophy, Judge PI, NIH R03AR056418, $327,930.
3. Heat shock protein 70, recovery of muscle mass & function following cast immobilization in old rats, Judge PI,
OAIC Pilot.
4. Role of NF kappa B and Foxo in the regulation of muscle atrophy genes and muscle atrophy during
experimental cancer cachexia, Judge PI, Bankhead-Coley Cancer Research Program, $231,744.
Sooyeon Kwon, PhD (Pharmacy) (April 2007 – June 2008) Mentor, Pamela Duncan, PhD (Aging)
Dr. Kwon relocated to the Medical University of South Carolina for family reasons in July 2008.
Papers Published/in Press: 2 (listed in RCDC section C.2.)
Todd Manini, PhD (Aging) (April 2007 – ongoing) Mentor, Marco Pahor, MD (Aging)
Papers Published/in Press: 27
Papers Submitted: 4
Grants Awarded
1. Acute responses to blood flow restricted exercise, Manini PI, OAIC Pilot, completed.
2. Resveratrol supplementation and memory dysfunction in older adults, Dual PI with Anton, McKnight Brain
Research Foundation, $100,000, completed.
3. The epidemiology of activity energy expenditure in late-life, Manini PI, American College of Sports Medicine,
$10,000, completed.
4. Myogenic and proteolytic regulators following blood flow restricted exercise, Manini PI, State of FL, $56,000,
completed.
5. Resveratrol for improved muscle lipid content in older adults, Manini PI, OAIC Pilot, completed.
6. Molecular mechanisms of skeletal muscle loss in HIV-infected older persons, Pahor, OAIC supplement NIH
P30AG028740-02S1, $146,500.
7. Chemotherapy, fatigue and functional limitation in older breast cancer survivors, Manini PI, Moffitt/Shands
Cancer Center, $44,939, completed.
8. Task-specific exercise for the pre-clinically disabled, Manini PI, NIH R21AG031974, $327,903.
9. Physical exercise to prevent disability, Pahor PI, NIH U01AG22376, $64,403,014.
10. OAIC pilot ARRA NOT-OD-09-058, Mitochondrial function and fatigue, Pahor PI, NIH P30AG028740.
Grants Pending
1. Haptic enhanced lower-limb prosthetic/orthotic for improved rehabilitation (HELPIR), Manini Site PI (Raj),
DOD
2. Chemotherapy-induced fatigue & functional limitation in older breast cancer survivors, R21AG031974 ACS
Chris DiMarco Grant
3. Blood flow restricted exercise – a novel method to promote skeletal muscle health (sub from Ohio Univ), NIH
DP2, $10,991.
4. Culturally sensitive spirituality-anchored health smart church center program, Tucker PI, NIH R21, $4,538
5. Longitudinal relationship between activity, energy expenditure, and function, NIH R01DK090049, $313,188.
6. Impact of physical activity on muscle strength, power and quality in aging, NIH R01AR057863, $577,394.
7. Tai-Chi to reduce physical disability among older adults, Roberts PI, NIH R01AG036880, $43,776.
Grants in Preparation
1. Non-exercise activity as a mediator of health in older adults, Manini PI, NIH R01, $2,158,247.
2. Non-exercise activity as a mediator of cardiovascular health in older adults, Manini PI, AHA, $431,250.
3. HIV and aging phenotypes, Manini PI, NIH R01, $1,465,000.
Grants Submitted, not Awarded
1. Mitochondrial dysfunction and the adipogenic phenotype in the elderly: effects of disability and exercise,
AFAR, $60,000.
2. Rehabilitation innovation: a novel approach to increasing skeletal muscle health (sub with Ohio U.), NIH
3. Wearable isotonic strength maintenance, NASA, $80,000.
4. Blood flow restricted exercise to prevent muscle dysfunction due to unloading, NASA, $125,000.
5. Thomas Maren junior investigator award, $80,000.
Emanuele Marzetti, MD, PhD (Aging) (April 2007 – March 2010) Mentor, Christiaan Leeuwenburgh, PhD
(Aging). Dr. Marzetti has relocated to the Catholic University in Rome, Italy where he holds an Assistant
Professor position.
Papers Published/in Press: 29
Papers Submitted: 1
Grants Pending
1. Myonuclear apoptosis in human sarcopenia, NIH RC2AG036551, Leeuwenburgh, $1,841,720
Grants Submitted not Awarded
1. Age-related changes in apoptosis signaling in human skeletal muscle, Marzetti PI, The Ellison Medical
Foundation, $400,000.
Formal Courses Taken
1. Structural Biochemistry, BCH 6740
2. Clinical and Translational Science Seminar Series, GMS 6893
2. Real Time qRT-PCR Hands On Training Workshop. From Tissue/Cells to Real time qRT-PCR
Bridgett Rahim-Williams, MA, MPH, PhD (Dentistry) (April 2007 – January 2011) Mentors, Roger Fillingim,
PhD (Dentistry); Elena Andresen (PHHP)
Papers Published/in Press: 3
Papers Submitted: 5
Grants Awarded
1. Pain, physical activity and functional mobility among women with knee osteoarthritis, Pahor PI, NIH,
$168,378.
Grants in Preparation
1. Exergaming for Physical Activity among Women with Type 2 Diabetes; NIH.
Grants Submitted, not Awarded
1. Pain, Physical Activity & Functional Mobility among Older Women with Knee Osteoarthritis (UF, CTSI).
Formal Courses Taken/Degrees Achieved
1. Issues & Concepts in Gerontology GEY 6646
2. Introduction to SAS
3. Biostatistics II GMS 5905”
4. Grant Writing in Epi & Health Policy Research GMS 6811
5. Graduate Certificate in Geriatric Care Management (Currently enrolled in program)
Stephanie Wohlgemuth, PhD (Aging) (April 2007 – March 2011) Mentor, Christiaan Leeuwenburgh, PhD
(Aging)
Papers Published/in Press: 12
Papers Submitted: 0
Grants Awarded:
1.Cummings PI. Study of energy and aging (SEA), NIH RC2AG036594, $261,197.
2.Pahor PI. OAIC pilot, ARRA NOT-OD-09-058, Mitochondrial function and fatigue, NIH P30AG028740,
$219,747.
Grants in Preparation
1.”Grand Opportunities”: Myocyte apoptosis in the development of sarcopenia and frailty at old age, NIH,
$2,021,000.
Grants Submitted, not Awarded
1.Wohlgemuth PI. Mitochondrial damage and autophagy in the aging heart, The Ellison Medical Foundation,
New Scholar in Aging, $200,000.
2.Wohlgemuth PI. AFAR. Autophagy and aging in prematurely aging transgenic Polg D257A mice, AFAR,
$59,999.
Dunn PI. Quality Control Mechanisms in Aging: Chaperone and Autophagy Responses, NIH R21, $50,034.
Formal Courses Taken:
1. Real Time qRT-PCR Hands On Training Workshop. From Tissue/Cells to Real time qRT-PCR.
Kevin Vincent, MD (Orthopedics) (May 2009 – ongoing) Mentor, Marco Pahor, MD (Aging)
Papers Published/in Press: 12
Grants Awarded:
1. An exploratory study of resistance exercise prehabilitation effects on physical function, psychosocial distress
and quality of life outcomes in patients undergoing treatment for soft tissue sarcoma, Vincent PI, Foundation for
Physical Medicine and Rehabilitation, $10,000, completed.
2. Resistance exercise and bone metabolism in stroke patients, Vincent PI, State of FL, $150,000, completed.
3. Comparative resistance exercise effects on knew osteoarthritis pain, functional impairment and cartilage
turnover, Vincent PI, K03AR059786, $219,750.
Grants in Preparation:
1. Relative Efficacy of Eccentric and Concentric Resistance Exercise on Knee Osteoarthritis Relative Efficacy of
Eccentric and Concentric Resistance Exercise on Knee Osteoarthritis Symptoms and Cartilage Turnover, Doris
Duke Charitable Foundation.
2. K23 Comparative Resistance Exercise Effects on Knee Osteoarthritis Pain, Functional Impairment and
Cartilage Turnover, NIH
Grants submitted, not awarded:
1. Eccentric Resistance Exercise Effects on Pain and Function in Knee OA, Arthritis Foundation
2. R03 Comparative Resistance Exercise Effects on Knee Osteoarthritis Pain, Functional Impairment and
Cartilage Turnover, NIH
Zvinka Zlatar, PhD Student (VA Brain Rehabilitation Research Outcomes Center - BRRC) (August 2008 –
ongoing) Mentor, Bruce Crosson, PhD (BRRC), Todd Manini, PhD (Aging)
Grants Awarded:
OAIC Minority Supplement, Pahor PI, NIHP30AG028740-01A3
Clinical Research Core (RC 1)
Leader: Susan Nayfield, M.D.
Phone: 352-273-5922
Fax: 352-273-5920
Email: [email protected]
The Clinical Research Core (RC 1) is a key resource for the UF OAIC in providing the infrastructure
and investigators for conducting clinical research -- randomized controlled trials and observational
studies. The clinical research core has four primary goals: 1) optimal selection and utilization of
measures for clinical trials and observational studies 2) understanding the physiological and
biomechanical mechanisms contributing to changes in walking speed, 3) in collaboration with the
Biostatistics and Data Management Core, conduct secondary analyses of randomized clinical trials and
observational studies to provide preliminary data to support the rationale for future clinical trials, and
4) development of behavioral and pharmacological interventions to improve physical function and
quality of life of older adults. The RC 1 offers state-of the art infrastructure and experienced personnel
to support the conduction of observational studies, and Phase 2 and 3 randomized controlled trials that
involve behavioral and pharmacological interventions. Senior researchers with NIH and VA funding,
who also have established track records as mentors for career development, lead each one of these
goals.
Specifically, the RC 1 conducts clinical research studies to assess, in conjunction with the Genomics
and Biomarkers Core, the effects of behavioral interventions (exercise and weight loss) on
inflammatory markers, oxidative stress, and apoptosis. Particular attention is being given to selection
and standardization of physical function and disability measures. The RC 1 supports the utilization of a
uniform battery of measures: physical function, biomechanics, disability, depression, and measures of
co-morbidity. State of the art and science facilities and muscle activated dynamic simulations of the
gait cycle are available to investigators to understand the biomechanical mechanisms that may explain
changes in walking. An experienced team of investigators supports development and standardization of
behavioral interventions.
Preclinical Research Core (RC 2)
Leader: Philip J. Scarpace, PhD
Phone: 352-392-8435
Fax: 352-392-9696
Co-Leader: Christy Carter, PhD
Phone: 352-273-5727
Fax: 352-273-5737
E-mail: [email protected]
Email: [email protected]
The Preclinical Research Core (PCRC) provides the infrastructure and investigators for conducting
preclinical research in rodent models of aging in order to test new interventions for preventing
disability. This approach is based on the similarities between age-related physical decline in humans
and rodents, and that interventional protocols designed to retard such declining physical function in
humans is limited by time and ethical constraints. We are engaging in an interactively translational
approach by which therapies are studied in rodents so that they may accelerate the pace of research in
humans, by 1) elucidating the biological mechanisms contributing to declining performance; and 2)
guiding future clinical treatments and trials by providing paradigms in which to test preclinical
interventions. Towards this end, the PCRC has three primary goals designed to enhance preclinical
rodent research, translational research, and educational and career development. As such, the PCRC
supports externally funded grants, development projects, pilot/exploratory studies, and career
development programs, all of which address the overall research theme of “Sarcopenia, prevention, and
rehabilitation of disability”.
Biostatistics and Data Management Core (RC 3)
Leader: Michael Daniels, Sc.D.
Phone: 352-273-6882
Fax: 352-273-5365
Email: [email protected]
The Biostatistics and Data Management Core is one of five research cores in the OAIC at UF. The
mission of the OAIC at UF is to assess risk factors of physical disability in older adults, to develop and
test effective prevention and rehabilitation therapies, and to train new investigators in research on aging
and disability. The Biostatistics and Data Management Core is a key cog in the interaction among
scientists from many disciplines to accomplish this mission. The core provides data coordination
including: developing data collection forms, designing web based capture systems, and managing the
data (including quality control) for studies conducted within the OAIC. The core also is involved in all
phases of these studies including initial study design and sample size calculations pre-proposal,
randomization, and state-of-the-art statistical analyses once the data are completed. For study designs
and data for which current methodology is lacking, the core has the expertise to develop new state of
the art methodology to perform correct and appropriate analyses of data collected in the Center. The
Biostatistics and Data Management Core will also be involved in preparation of manuscripts for
dissemination within the research community.
Recruitment Core (RC 4)
Core Leader: Michael Marsiske, Ph.D.
Phone: 352-273-5097
Fax:
Co-Leader: Susan Nayfield, MD
Phone: 352-273-5922
Fax: 352-273-5920
Email: [email protected]
Email: [email protected]
The Recruitment Core provides services to support recruitment, including development and
implementation of recruitment strategies, monitoring and reporting recruitment progress, and
development of recruitment materials. The Recruitment Core will also help OAIC-affiliated studies and
investigators, with a particular emphasis on Pepper Junior Scholars, to develop strategies for
monitoring and improving participants’ adherence and retention in clinical research studies. Core
investigators have substantial experience with the recruitment of older adults, especially persons of
color, both in the Gainesville/Alachua County region, and in other settings nationally. The presence of
a dedicated core also facilitates enrollment of women, ethnic minorities, and elders with disabilities, all
of whom have often been under-represented in both observational and intervention studies. The
Recruitment Core also has a scientific focus, conducting studies to (1) evaluate the success of strategies
to facilitate participation, retention and adherence in OAIC-associated research, and 2) to identify the
most effective and efficient RAR strategies. In both the services provided and studies conducted by the
Recruitment Core, a particular emphasis will be on the participation of ethnic minorities and persons
with physical disability into research on aging.
Genomics and Biomarkers Core (RC 5)
Core Leader: Christiaan Leeuwenburgh, Ph.D.
Phone: 352-273-6796
Fax: 352-273-5920
Email: [email protected]
The Genomics and Biomarkers Core provides the infrastructure, laboratory space, trained personnel,
consultative and collaborative scientific expertise and a wide spectrum of established methodologies of
biochemistry and molecular biology (Northern, Western blot and Quantitative-PCR, enzyme-linked
immunosorbent assays), genome-wide gene expression analysis using a novel microarray technology,
analytical chemistry (liquid chromatography-mass spectrometry-mass spectrometry and gas
chromatography mass spectrometry using stable isotope dilution techniques) and selected measures of
metabolism (i.e., ATP measures and enzymes of metabolism) that will address a set of genetic and
biological themes focused on causes for sarcopenia and disability. The Genomics and Biomarkers Core
utilizes this state-of-the-art technology to determine specific mechanisms of sarcopenia and the cause
of reduced physical function present in elderly populations. The Core provides support for numerous
independently funded studies, development projects, pilot studies and exploratory studies. Analyses of
levels of biomarkers or cell signaling molecules will help to identify specific biological pathways of
aging implicated in the development of sarcopenia. If the precise mechanisms underlying ageassociated cellular deterioration can be identified, it will explain the loss of muscle mass and function
with age and provide us with potential targets for intervention. In this context, we will also test if
specific rehabilitation, physical activity and dietary interventions can attenuate biological pathways
leading to sarcopenia and functional impairment.
Pilots/Exploratory Studies Core (PEC)
Core Leader: Christy S. Carter, Ph.D.
Phone: 352-273-5727
Fax: 352-273-5737
Co-Leader: Susan Nayfield, M.D.
Phone: 352-273-5922
Fax: 352-273-5920
Email: [email protected]
Email: [email protected]
The Pilot/Exploratory Studies Core serves to develop key information needed to select and design
future, original and independently funded studies that can advance our insight into sarcopenia,
prevention, and rehabilitation of disability in older Americans. Specifically, the core fosters the Pilot
and Exploratory studies by ensuring the availability of optimal infrastructure, environment, funding,
expertise, and instrumentation. Pilot and Exploratory studies foster Junior Scholars in their efforts to
develop research careers in aging by providing opportunities for meaningful participation in welldesigned research studies and by collecting the needed preliminary data for independent research
applications. Furthermore, these studies will allow investigators already accomplished in aging
research to gather data that will extend and broaden their focus of research. Finally, these studies will
also be a vehicle to encourage and facilitate experienced investigators traditionally working in other
research fields to focus on aging.
B. RESEARCH
The UF OAIC has demonstrated outstanding productivity in supporting and contributing to externally
funded grants through its integrated Core infrastructure, pilot funding and mentoring. The UF OAIC
supports and contributes to a total of 87 active grants with a total cost of $173 million (Table 3a). Of
the 87 active grants, 10 were awarded in the past 18 months. The UF OAIC has also supported 38
grants that have been completed.
Table 3a. OAIC support and contributions to active external grants
Award
Date
Proposed
End Date
Source
OAIC
Core
support
7/1/2007
3/31/2012
CDC
U59DD000273
RCDC,
RC 1
10/1/2008
9/30/2013
National Institute
on Disability and
Rehabilitation
Research
U59DD000266
RC 1
Andresen, E
(Miller)
7/1/2007
4/30/2012
NIH R01AG010436
RCDC
Anton, S
7/1/2009
6/30/2011
AHA
09CRP2390173
PESC
RCDC,
RC 1,
2, 3, 4
Title of Grant
PI
Florida disability &
health project (state
capacity building)
Andresen, E
Disability and
rehabilitation
research project on
health disparities and
disabilities
Andresen, E
(Drum)
Physical frailty in
urban African
Americans
Dose response
effects of weight loss
on oxidative stress
and inflammation
Investigations of
botanicals on food
intake, satiety,
weight loss and
oxidative stress
Anton, S
9/1/2009
8/31/2014
NIH K23AT004251
PESC
RCDC,
RC 1,
2, 3, 4
Resveratrol for
improved
performance in the
elderly: the RIPE trial
Anton, S
1/1/2010
12/31/2011
Thomas Maren Jr
Invest. Award
PESC
RCDC,
RC 1
Beginning to teach
safe hospital
discharge
Bautista, M
8/2/2010
6/17/2011
UF Award
Guideline adherence
in elders with heart
failure and multiple
comorbidities
Beyth, R
(Steinman)
7/1/2007
6/30/2011
VA HSRD IIR
RCDC
Biopsychosocial
influence on
shoulder pain
Borsa (George)
6/30/2008
5/31/2012
NIH R01AR055899
RC 2
PESC
Bone Content and
Metabolism of Sex
Steroid Hormones
Borst, S
10/1/2009
9/30/2013
1I01RX000142-01
RC 2
Graded vascular
occlusion
Buford, T
4/1/2010
4/20/2011
American College
of Sports Medicine
RCDC,
RC 1, 3,
4
Muscle regeneration
and sarcopenia
Buford, T
1/1/2010
6/30/2011
Merck 37268
RCDC,
RC1, 2,
3, 4
Role of skeletal
muscle blood flow in
regeneration and
sarcopenia (CTSI)
Buford, T
(Nelson)
8/20/2009
3/31/2011
NIH L2RR02988
RCDC,
RC1, 2,
3, 4
ACE inhibition and
physical
performance in aged
rats
Carter, C
8/1/2005
7/31/2011
NIH R01AG024526
RC
2,3,5,
PESC
Obesity and age
impaired physical
performance: gene
therapy
Carter, C
2/15/2008
2/14/2011
VA GRECC
contract
RC 5
PESC
Chmielewski, T
9/30/2007
8/31/2012
NIH K01HD052713
RC 2
Dahm, P
7/1/2009
6/30/2011
American
Geriatrics Society
RCDC
Dahm, P
7/1/2008
6/30/2011
Society of Urology
Chairpersons
RCDC
Bayesian methods
for (Incomplete)
longitudinal cancer
data
Daniels, M
6/1/2009
5/31/2013
NIH R01CA085295
PESC
RC 3
New approaches to
mediation analysis
using causal
inference methods
Daniels, M
(Hogan)
9/30/2009
8/31/2011
NIH
RC1AA019186
PESC
RC 3
Mitochondrial
dysfunction and the
role of autophagy in
cardiomyocytes
Dutta, P
(Leeuwenburgh)
7/1/2010
6/30/2012
AHA
10PRE4310091
RC 2
3/31/2011
Univ of Medicine
and Dentistry of
New Jersey
Foundation
7/31/2011
Univ of Medicine
and Dentistry of
New Jersey
Foundation
Muscle weakness
and post-traumatic
knee
Evidence based
decision making in
geriatric
genitourinary
oncology
Evidence based
medicine training in
urology residency
Validation of an
improved method to
study mycobacterium
tuberculosis
transmission in
humans
Fennelly, K
Positron emission
tomography with F18 flurodeoxyglucose
to identify early
events in latent
infection with
mycobacterium
tuberculosis
Fennelly, K
(Ghesani)
4/1/2009
8/1/2009
Sex-related genetic
influences on pain
and analgesia
Fillingim, R
9/1/2000
7/31/2011
NIH R01NS041670
RCDC,
RC 3
Ethnic differences in
responses to painful
stimuli
Fillingim/RahimWilliams
9/30/2009
8/31/2011
NIH R01AG033906
RCDC,
RC 1, 4
Mechanisms for
altered synaptic
function during aging
Foster, T
(Leeuwenburgh)
5/15/2004
5/31/2012
NIH R01AG014979
RC 2, 5
Estrogen and
cognition over the
lifespan
Foster, T
3/16/2004
2/28/2011
NIH
R01MH059891
RC 2, 5
Cellular events in
heritable peripheral
neuropathies
Foster, T
(Notterpek)
7/1/2005
5/31/2014
NIH R01NS041012
RC 2, 5
Signaling cascades
and memory deficits
during aging
Foster, T
12/1/2010
11/30/2014
NIH
R01AG03680001A1
RC 2
Role of NF kappa B
and Foxo in the
regulation of muscle
atrophy genes and
muscle atrophy
during experimental
cancer cachexia
Judge, A
7/1/2009
6/30/2012
Bankhead-Coley
Cancer Research
Program 09BN-09
PESC
RC 5
Heat shock proteins
and disuse muscle
atrophy
Judge, A
3/1/2009
2/28/2012
NIH R03AR056418
PESC
RC 2, 5
PESC
K8RC 5
Cytokine-induced
muscle atrophy
following exercise
claudication
Judge, A
7/1/2008
6/30/2011
James and Esther
King Biomedical
Research Program
08KN-07
Intermuscular
coordination of
hemiparetic walking
Kautz, S
6/1/2004
8/31/2011
NIH R01HD046820
RCDC
Autophagy in liver
injury
Kim, J-S
3/5/2009
12/31/2013
NIH R01DK079879
RC 2
ZIP proteins and iron
metabolism
Knutson, M
8/1/2008
7/31/2013
NIH R01DK080706
RC 2
Study of Energy and
Aging
Leeuwenburgh,
C (Cummings)
9/30/2009
8/31/2011
NIH
RC2AG036594
RCDC
RC 2
PESC
Molecular
mechanisms of
oxidative stress in
aging muscle
Leeuwenburgh,
C
7/1/2006
6/30/2011
NIH R01AG017994
RC 2
Diaphragm
mitochondrial
dysfunction during
prolonged
mechanical
ventilation (CTSI)
Leeuwenburgh,
C (Nelson)
12/1/2009
11/30/2010
NIH L2RR02988
RCDC,
RC 1
Women's health
initiative
Limacher, M
9/30/1994
9/29/2010
NIH N01WH42129
RCDC
Women's health
initiative memory
study MRI-2
Limacher, M
8/1/2008
12/31/2010
NIH
N01WH424221
RCDC
Women's Health
Initiative Extension
2010-2015
Limacher, M
10/1/2010
90/30/11
WFUHS 30305
RCDC
Task specific
exercise for the
clinically disabled
Manini, T
9/15/2009
8/31/2011
NIH R21AG031974
RCDC,
RC 1,
2, 3, 4
PESC
ACTIVE Phase III:
UF/WSU Field Site
Marsiske, M
5/1/2006
3/27/2011
NIH U01AG014276
RC 4
Physical, cognitive
and mental health in
social contact
Marsiske, M
7/1/2002
4/30/2013
NIH T32AG020499
RCDC
Platform for multimodal cognitive
enhancement in the
elderly (the wellness
study)
Marsiske, M
(Bowers, D)
7/2/2010
7/1/2013
McKnight Brain
Research
Foundation
RC 4
Genetic variation of
allele-specific
transcriptome in
drosophila
McIntyre, L
2/1/2007
1/31/2011
NIH
R01GM077618
RC 2, 3
Novel 5HT2C
agonist drugs with
5HT2A antagonist
activity for cocaine
addiction
Morgan (Booth)
9/30/2007
8/31/2011
NIH R01DA023928
RCDC,
RC5
Aspirin in reducing
events in the elderly
Nayfield, S
(Grimm)
9/15/2009
8/31/2016
NIH U01AG029824
RC 1,
2, 4
RCDC,
LAC,
RC 1, 2,
3, 4
UF clinical and
translational science
award
Nelson, D
7/14/2009
3/31/2014
NIH U54RR025208
Aerobic exercise to
improve executive
language function in
older adults
Nocera, J
10/1/2009
9/30/2011
Veterans Affairs
E6860M
Hormonal control of
plasticity of
neurogenesis:
understanding gene
dynamics memory
Ogle, W
7/1/2006
6/30/2011
Ellison Med.
Found. AG-NS-0373-06
RCDC
Institute on Aging
clinical translational
research building
Pahor, M
1/14/2010
1/13/2015
NIH C06RR029852
RCDC,
RC 1, 2,
3, 4, 5,
PESC
The LIFE study
Pahor, M
9/1/2009
8/31/2015
NIH U01AG022376
RCDC,
RC 1, 2,
3, 4
PESC
8/31/2015
NIH U01
AG022376-05A2
RCDC
RC 1, 2,
3, 4
PESC
The LIFE study
Pahor, M
4/1/2010
Cognitive aging and
memory clinical
translational
research program
Pahor, M
6/1/2009
5/31/2014
McKnight Brain
Research
Foundation
RC 1,
3, 4
Exercise training and
inflammatory risk
factors for disability
Pahor, M
(Nicklas)
9/15/2006
8/31/2011
NIH R01AG027529
RC 1
Latent mobility
abnormalities and
frailty
Pahor, M
(Verghese)
8/1/2005
6/30/2011
NIH R01AG025119
RC 1
Pahor, M
9/30/2009
8/31/2011
NIH
P30AG02874003S1
RCDC,
RC 1, 2,
3, 4
Pahor, Manini
9/1/2008
3/31/2012
NIH
P30AG02874002S1
RCDC,
RC 1, 2,
3, 4
OAIC Supp-Physical
activity, pain and
functional mobility
among
women..diversity (B.
Rahim-Williams)
Pahor, M
9/30/2008
3/31/2011
NIH
P30AG02874002S2
RCDC,
RC 1, 4
OAIC Supp Diversity Z. Zlatar
Pahor, M
1/1/2009
3/31/2011
OAIC Supp - RCDC
projects
Pahor, M
9/30/2009
3/31/2012
Oxidative damage,
disability and
mortality in elders
Pahor, M
7/1/2007
6/30/2011
NIH R01AG026556
RC 1,
RC 2
Testosterone trial
Pahor, M
(Snyder)
4/15/2009
4/30/2015
NIH U01AG030644
PESC,
RCDC,
RC 1, 4
Perri, M
6/1/2008
5/31/2013
NIH R18HL087800
PESC
Perri, M
(Janicke)
8/1/2009
7/31/2014
NIH R18DK082374
RCDC
Perri, M
(Kiernan)
7/11/2007
5/31/2011
NIH R01CA112594
RCDC
Perri, M (Helal)
9/26/2007
7/31/2011
NIH R21DA024294
RCDC
Perri, M
(Rejeski)
8/1/2005
4/30/2011
NIH R01HL076441
RC 1
Perri, M (Pahor)
8/1/2005
4/30/2010
NIH/NHLBI
R01HL076441-01
RC 1
OAIC pilot study
"Mitochondrial
function and fatigue"
OAIC Supp.Molecular
mechanisms of
skeletal muscle loss
in HIV-infected older
persons
Rural lifestyle
intervention
treatment
effectiveness trial
(rural LITE)
Extension family
lifestyle intervention
project
Promoting healthy
weight with "stability
first"
Smart home-based
health platform for
behavioral
monitoring diabetes
and obesity
Cooperative lifestyle
intervention program
Claude D Pepper
Older American
Independence
Center (OAIC)
NIH
P30AG02874001A3
NIH
P30AG02874003S2
RCDC,
RC 1
RCDC
Training in the
neurobiology of
aging
Scarpace, P
5/1/2007
4/30/2012
NIH T32AG000196
RCDC,
RC 5
PESC
CMS nonpayment for
nosocomial injury
and the risk of falls in
hospitals
Shorr, R
9/30/2009
8/31/2011
NIH R01AG033005
RC 1
Depressed mood
and anti-depressant
treatment among
post-stroke veterans
Shorr, R
4/1/2009
3/31/2014
VA-822 Rehab
Research
RC 1
Gait and balance
assessment with live
video from the
computerized patient
record system
(CPRS) interface
with vista imaging
Shorr, R
7/1/2009
6/30/2011
VA (Greenfield
Innovators Award)
RC 1
Systolic blood
pressure intervention
trial (SPRINT)
clinical center
networks
Shorr, R
9/1/2010
9/1/2011
Research, INC (VA
non-profit
foundation)
RC 1
Web-based
informational
materials for stroke
caregivers
Uphold, C
5/1/2008
4/30/2011
VA SDP 06 -237
RCDC
Vandenborne, K
9/28/2004
1/31/2011
NIH R01HD048051
Rehabilitation
research career
development
program
Vandenborne, K
(Ottenbacher)
9/25/2007
8/31/2012
NIH K12HD055929
RCDC
Interdisciplinary
training in
rehabilitation and
neuromuscular
plasticity
Vandenborne, K
6/11/2003
4/30/2013
NIH T32HD043730
LAC,
RCDC
Developing a
computer adaptive
test for assessing
safety after traumatic
brain injury
Velozo, C (Seel)
10/1/2008
9/30/2011
Shepherd Center
PESC
RC1
Velozo, C
(Shulman)
9/30/2009
7/31/2013
NIH U01AR057967
PESC
RC1
Vincent, K
7/9/2010
5/31/2013
NIH R03AR059786
PESC,
RCDC,
RC 4
Wohlgemuth, S
(Cummings)
9/30/2009
8/31/2011
NIH
RC2AG036594
RC 2
Molecular signatures
of muscle
rehabilitation
Development and
validation of a selfefficacy item bank
Comparative
resistance exercise
effects on knew
osteoarthritis pain,
functional
impairment and
cartilage turnover
Study of energy and
aging
RCDC
AHA fellowship
Xu, J
7/1/2009
6/30/2011
AHA
09POST2060112
RC 2
Integrative and
translational training
in pain research
Yezierski, R
7/1/2005
6/30/2015
NIH T32NS045551
RC 5
Effects of age on
thermal sensitivity
Yezierski, R
9/30/2008
8/31/2011
NIH R21AG031821
RC 5
Leptin function and
resistance in
midbrain VTA & SN
in reward eating and
obesity
Zhang, X
(Scarpace)
10/1/2009
9/30/2013
VA Merit Review
PESC
RC 5
Active
Grants
87
Table 3b. OAIC support and contributions to completed external grants
Award
Date
End Date
Source
Anton/Perri
5/1/2006
6/30/2009
UF Opportunity
Fund
RCDC, RC1,
2, 3, 4, PESC
Anton (Shapiro)
1/1/2008
1/1/2009
UF Opportunity
Fund
RC5
Anton/Manini
1/1/2008
9/30/2010
McKnight Brain
Research
Foundation
PESC,
RCDC, RC1,
3, 4
Beyth, R
(Uphold)
10/1/2002
9/30/2009
NIH
R01HL070794
RCDC
Effects of EECP on arterial
function
Braith, R
8/15/2004
7/31/2009
NIH
R01HL077571
RCDC
Adapting tools to
implement stroke risk
management to veterans
Damush, T
(Beyth)
7/1/2006
6/30/2009
VA Health
Services
Research and
Development
RCDC
Beyth/Shorr
7/1/2008
6/30/2010
Am. Geriatric
Society
RCDC
Title of Grant
Biological effects of weight
loss plus exercise in older
obese African-American
women
Prevention of age-related
obesity, sarcopenia, and
decline in physical
performance through
synergistic effect of leptin
and wheel running
Resveratrol
supplementation and
memory dysfunction in
older adults
Improving anti-thrombotic
use for stroke prevention
Evidence based decision
making in geriatric
genitourinary oncology
Effect of plyometric
exercise on function &
articular cartilage
metabolism after ACL
reconstruction
Urinary levels of
osteoarthritis biomarkers
during the early period
after ACL reconstruction
Resident educational grant
PI
Chmielewski, T
(Leeuwenburgh)
National
Football
League
OAIC Core
support
7/1/2007
8/13/2010
RC 2
Chmielewski, T
(Leeuwenburgh)
7/7/2009
9/30/2010
UF Foundation
007474
RC 2
Dahm, P
7/1/2008
7/21/2010
Am. Geriatric
Society
RCDC
Locomotor experience
applied post stroke
(LEAPS)
Computer adaptive
measure for cognitive
stroke
NIH
R01NS050506
Duncan, P
9/25/2005
6/3/2007
Duncan, P
(Velozo)
3/1/2006
4/9/2009
Neuromechanical modeling
of human movement
Kautz, S
2/15/008
2/14/2009
Function, characterization
& stability of bioactive
hydrolysates peptides
Kristinsson, H
9/1/2006
8/31/2009
USDA 220635503-1755
RC 2
DNA/RNA/urine oxidative
damage analysis
Leeuwenburgh,
C
5/5/2008
5/4/2009
Lifegen Tech.
RC 5
Apoptosis and life-long
caloric restriction
Leeuwenburgh,
C
8/1/2003
7/31/2009
NIH
R01AG021042
RC 2
Eufortin/Sharper study
Leeuwenburgh,
C
11/1/2007
12/31/2009
Sharper
RC 2
Limacher, M
9/1/1999
5/31/2010
NIH
K30RR022258
RCDC
Manini, T
1/1/2009
12/31/2009
Moffitt Cancer
Center
RCDC, RC
1, 3, 4
Advanced postgraduate
program in clinical
investigation
Chemotherapy, weakness
& function in older breast
cancer survivors
Glaxo
SmithKline
VA Medical
Center
VA248PO405
RC 1, 4
RC 1, 4
RCDC
RCDC,RC1,2,
3, 4
Manini, T
7/1/2008
5/11/2010
American
College of
Sports
Medicine
Manini, T
1/1/2008
6/30/2009
State of Florida
RCDC, RC
1, 3, 4, PESC
Marsiske, M
(Belchoir)
5/1/2008
4/30/2010
Robert Wood J
Foundation
RC 4
Chronic opioids and aging
Morgan, D
7/1/2007
5/31/2010
NIH
R21DA023022
RC 5
Testosterone trial IVR pilot
#2
The epidemiology of stress
and the metabolic
syndrome
Physical exercise to
prevent disability pilot
study (LIFE-P)
Treatment of obesity in
underserved rural settings
- TOURS
Pahor, M
(Snyder)
9/15/2005
8/31/2009
NIH
U01AG027016
RCDC, RC 1,
4
Pahor, M
10/1/2005
8/31/2008
NIH
R01HL072972
RC 1, 3
Pahor, M
9/1/2005
8/31/2009
NIH
U01AG022376
RC 1
Perri, M
6/1/2003
5/31/2008
NIH
R01HL073326
RCDC
RC 1
The epidemiology of
activity energy expenditure
in late life
Myogenic and proteolytic
regulators following blood
flow restricted exercise
Action video games to
improve cognitive function
in elders
Effects of Tai Chi on
physical performance,
functional limitation and
disability
Roberts, B
7/1/2006
11/30/2007
University of
Florida
Opportunity
Grant
Leptin resistance: 1
mechanism underlying
age-related obesity
Scarpace, P
(Tumer)
9/1/2004
8/31/2010
NIH
R01AG026159
PESC RC 5
Obesity and age impaired
physical performance:
gene therapy
Scarpace, P
(Tumer)
9/1/2007
8/1/2010
VA Merit
Review
RC 5
Trial of proximity alarms to
reduce patient falls
Shorr, R
6/1/2007
4/30/2009
NIH
R01AG025285
RCDC
Institutional CTSA planning
grant
Stacpoole, P
9/21/2006
9/20/2008
NIH
P20RR023488
LAC, RCDC,
RC 1
Obesity and age impaired
physical performance:
gene therapy
Tumer, N
1/1/2007
12/31/2009
VA GRECC
4770
PESC RC 5
Angiotensen II and tyrosine
hydroxylase with age
Tumer, N
1/1/2007
9/30/2008
VA 003
RC 5
Dissemination evaluation
of educational materials for
Puerto Rican OIF/OEF
veterans and families
Uphold, C
8/25/2008
9/31/09
VA Health
Services and
Development
RC 1
An exploratory study of
resistance exercise
prehabilitation effects on
physical function,
psychosocial distress and
quality of life outcomes in
patients undergoing
treatment for soft tissue
sarcoma
Vincent, K
10/1/2009
9/30/2010
Foundation for
Physical
Medicine and
Rehabilitation
PESC,
RCDC, RC 4
Vincent, K
1/1/2008
3/12/2009
State of Florida
PESC,
RCDC, RC 4
Walter, G
9/1/2004
8/31/2009
NIH
R01HL78670
RC 5
Resistance exercise and
bone metabolism in stroke
patients
Non invasive monitoring
and tracking of muscle
stem cells
Completed
Grants
38
C. PILOT/EXPLORATORY PROJECTS
During the first 4 years, the UF OAIC has supported 5 research development projects and 21 pilot and
exploratory studies. The OAIC investigators have been extremely productive in leveraging the pilot
studies to submit larger independent grants.
Research Development Projects
Project Title: Clinical tolerance of the microbiopsy and the Bergstrom muscle biopsy technique
Project Leader: Christiaan Leeuwenburgh/Thomas Buford
The analyses offered and performed by the Older American Independence Center (OAIC) Biomarkers
and Metabolism Core are closely linked to apoptosis, oxidative stress, inflammation and measures of
mitochondrial function in tissues such as blood, urine and skeletal muscle. Mitochondrial dysfunction
is central to the aging process and the pathogenesis of diseases. A primary objective of this Core is to
assess mitochondrial function in skeletal muscle from elderly subjects, and to correlate these measures
with the subject’s physical performance. To obtain skeletal muscle samples from human participants,
the Core has traditionally utilized the large bore Bergström needle technique. This technique ensures
large tissue yields, but bears the risk for discomfort and pain, especially in elderly subjects. To avoid
these adverse events, it becomes essential to identify, develop, test and optimize minimally invasive
techniques of tissue acquisition, particularly for large clinical trials with the elderly. The main focus of
this Development project is, therefore, to compare a skeletal muscle microbiopsy technique with the
traditional Bergström technique. In contrast to the traditional technique, the microbiopsy relies on a
small 16-gauge disposable needle. The consequentially reduced invasiveness holds great potential for
its applicability in large clinical trials. The aims of this study are threefold. We will compare the
minimally invasive microbiopsy and the traditional Bergström technique with regard to 1) perceived
pain by research subjects; 2) their evaluation by the operating physicians; and 3) the tissue yield and
quality for mitochondrial function measurements. We hypothesize that the microbiopsy technique will
lead to less pain in the subjects, will be the preferred method by the physician, and still provide the
minimal sample amount needed to assess mitochondrial function in skeletal muscle. The proposed
project will take advantage of an ongoing study, the Developmental Project (OAIC RC5 RD1), and
thereby substantially maximize cost-effectiveness. The subjects of this ongoing Developmental Project
are young healthy adults and healthy elderly research participants. To achieve the proposed aims, we
will perform muscle biopsies of the vastus lateralis on each leg. One leg will be biopsied using the
traditional Bergström technique and the other will be biopsied using the microbiopsy technique.
Patients and physicians will fill in questionnaires related to the procedures. Mitochondrial function
will be assessed and quantified in each of the biopsy specimens to determine the quantity of
mitochondria and to compare their quality. If this new procedure for the OAIC shows to be more
efficacious, this will allow us to quickly test skeletal muscle mitochondrial bioenergetics and their
correlation with clinical interventions (e.g., life style, exercise, pharmacological, nutritional) using a
technique that is less invasive for participants.
Project Title: Non-invasive approaches to study skeletal muscle O2 delivery and utilization
Project Leader: Susan Nayfield/Todd Manini
A primary focus of the Clinical Research Core (CRC) is to build a biological understanding of causes
and consequences of losses in physical function and disability among older adults. Ongoing research by
the CRC frequently uses muscle biopsies to accomplish this goal, adding burden and discomfort to
participants that directly influences recruitment and adherence in all studies. The overarching aim of
this project is to provide the resources to implement and clinically evaluate non-invasive imaging
techniques to investigate blood flow, tissue perfusion and mitochondrial function that are major factors
that lie in the pathway to aging of skeletal muscle mass and loss in physical function. Such assessments
are critical in understanding the etiology of sarcopenia in humans and are well suited for the scope of
the OAIC’s mission. The goal will be to implement an efficient nuclear magnetic resonance (NMR)
protocol to fully assess blood flow, tissue perfusion and mitochondrial function in a single visit that
will minimize expensive MRI and staff time as well as participant burden. Specifically, we will assess
peripheral blood flow using Phase Contrast Imaging (PCI), muscle perfusion via Arterial Spin Labeling
(ASL), and O2 metabolism via 31P Spectroscopy. To accomplish the implementation phase of the
study we will consult with the world’s experts who have agreed to assist our efforts. We will also
support an educator who can implement the technology on the specific MRI equipment being used by
the CRC. Our efforts will lead to further collaborations across the University of Florida by providing
new tools to access cardiovascular function and energy metabolism making the CRC a resource for
researchers at large. We will finalize our goals by conducting a reliability and validity study that will
provide evidence of proficiency in conducting the evaluations. First, we will compare healthy older
adults to patients with peripheral arterial disease to establish that we can detect differences in muscle
physiology in differing clinical conditions using the newly developed techniques. We will then
established test-retest reliability of these techniques in healthy older and PAD patients. The completion
of project will provide the CRC a thorough evaluation of O2 delivery and utilization in a single
package thus reducing participant burden while maximizing cost effectiveness.
Project Title: Models to Reduce Adiposity and Oxidative Stress
Project Leader: Phillip Scarpace, PhD
This development project is evaluating interventional models that modulate adiposity in aged rats for
assessing effects on physical function, inflammation, oxidative stress, apoptosis, and sarcopenia. This
study will set the basis and methodologies for preclinical testing of other weight lowering interventions
on relevant age-related outcomes.
The central hypothesis of this development project is that increased adiposity with age contributes to
two age-related outcomes: 1) a decline in physical performance; and 2) changes in muscle quality as
measured by increased oxidative stress, inflammation, and subsequent apoptosis in skeletal muscle. We
have established several relevant interventional strategies to reduce or increase adiposity in the Fischer
344/Brown Norway (F344xBN) rat, a well-established animal model of aging. F344xBN rats
demonstrate declining physical performance, occurring in the context of a steady increase in body
weight and adiposity into early senescence followed by a decline, similar to what occurs in humans (1).
We will employ one paradigm that elevates adiposity (fat-feeding) and should further reduce physical
performance in aged rats, and two interventions that reduce adiposity (mild 8% caloric restriction and
POMC gene therapy) and should restore physical performance. Subsequently, we will assess muscle
quality, in the context of each of these interventions. We are addressing the following specific aims: 1)
Does high-fat feeding exacerbate the already elevated oxidative stress/inflammatory status with age
and accelerate the decline in physical performance? 2) Aged rats are obese and, similar to obese
humans are profoundly leptin resistant. Therefore, does activation of the central melanocortin pathway
(through POMC gene therapy) circumvent leptin resistance and evoke weight loss in aged-obese rats,
ameliorate the elevated oxidative stress/inflammatory status with age and lead to improved physical
performance? 3) Does short-term, mild (8%) CR prevent the decline in physical performance with age?
Thus, these studies will compare the effects of either adiposity inducing or reducing interventions in a
model of age-related physical decline, and link these outcomes to dysregulation of muscle quality.
The first phase of the developmental project was completed in the first year, in which the responses of
aged rats to high-fat (HF) feeding were examined. Results indicated aged rats ate more food, gained
more fat and weight compared with young. In addition, high-fat feeding decreased the tendency for
wheel running, suggesting the propensity for inactivity with age and high-fat feeding may contribute to
the accelerated the rate of diet-induced obesity. These results demonstrate that aged rats are more
susceptible to the detrimental effects of a high fat diet. The second phase of study was completed in
second year examining gene delivery of anorexic agents to prevent and reverse obesity and the decline
in physical activity with age. We discovered that leptin synergized with wheel running (WR) to greatly
reduced obestiy and improved metabolich parameters. The mechanism appears to involve a restoration
in the age and obesity impared decline in leptin signaling. In the third year, we discoved that small
amounts of WR, that were without effect in young rats, decreased body weight and increased physical
performance in aged rats. Intervention in aged rats with POMC gene delivery revealed that
overexpression in the ventral tagmental area or hypothalamus was effective at detering high-fat feeding
mediated weight gain. Data collected from this Developmental project supported the funding of one
VA Merit application in 2009 and the submission of a NIH grant currently under review, an American
Heart application under review, a VA Merit application in preparation. Study is complete.
Project Title: Longitudinal Examination of Physical Performance
Project Leader: Michael Daniels, PhD
This developmental project uses a data set from an RO1 grant, “ACE Inhibition (ACEi) and Physical
Performance in Aged Rats” (NIH R01 AG024526-02, PI Dr. Christy Carter) to develop statistical
methodologies that will have application to the study of longitudinal assessment of physical
performance in aged rats and humans. Specifically, we are refining our understanding of the
relationship between pathophysiological changes and declining physical performance and ultimately
can design better interventions to attenuate/reverse these changes. Therefore, we will develop new
methodology for assessing modeling trajectories from different longitudinal processes (declining
physical performance, muscle pathophysiology, and longevity).
Project Title: Skeletal Muscle Apoptosis and Physical Performance/Oxidative RNA/DNA
Damage and Repair in Aged Human Muscle
Project Leader: Christiaan Leeuwenburgh, PhD
The objectives of the study are (1) to assess the extent of muscle apoptosis in old low- and high
functioning subjects and to verify the presence of an association between muscle apoptosis, sarcopenia
and physical disability. (2) to correlate levels of RNA and DNA oxidation with muscle mass and
strength, and (3) to quantify gene expression of DNA repairing enzymes in old low- and highfunctioning subjects.
Pilots and Exploratory Studies
Project Title: Locomotor reserve: a novel approach for detecting mobility deficits with aging
Project Leader: David J. Clark
This goal of the proposed project is to produce high-quality pilot data to support an externally funded
line of research for early detection of age-related mobility deficits, specifically with regard to emerging
neuromuscular impairment. We propose the concept of a “locomotor reserve” to provide a novel and
promising approach by which physical assessments can be used to detect and probe the neuromuscular
determinants of emerging mobility disability. Locomotor reserve is operationally defined here as the
ability to increase locomotor output over and above usual locomotor output. This proposal will focus
on walking speed reserve (% difference between usual and fastest walking speeds) and step length
reserve (% difference between usual and longest step lengths while walking). We expect that increasing
speed and step length during a brief walking assessment primarily challenges the neuromuscular
system, and may thus provide unique insight to neuromuscular factors affecting mobility function. We
will recruit older adults to two experimental groups (n=10 participants per group). Participants in both
groups will have usual walking speed in the range of 1.0-1.4 m/s, which has been described as a
“normal” range. The decision to recruit relatively high functioning participants is consistent with our
objective of establishing assessments for early detection of mobility deficits. The difference between
the groups will be the magnitude of walking speed reserve. The group with higher walking speed
reserve (“HIGH”) will be capable of increasing walking speed by at least .8 m/s. The group with lower
walking speed reserve (“LOW”) will be capable of increasing walking speed by .6 m/s or less. Muscle
volume, intermuscular adipose, walking biomechanics and neural control will be assessed in order to
determine the factors underlying differences in locomotor reserve.
Project Title: Respiratory sarcopenia and chronic lung infections in elderly women
Project Leader: Kevin P. Fennelly
Chronic lung disease is a major cause of disability among elderly persons around the world, but little
attention has been paid to the role of respiratory muscle weakness associated with the aging in the
functional limitation associated with these diseases. Pulmonary nontuberculous mycobacterial (NTM)
is a well-defined, specific type of chronic lung disease that has been increasingly recognized in elderly
women who have been previously healthy. However, the etiology of this disorder is unknown. The
only risk factor other than age in a recent study was low body mass index. We hypothesize that these
women have 'respiratory sarcopenia', i.e., respiratory muscle weakness that has worsened with age for a
variety of factors, and that a result of this weakness is ineffective cough clearance of the airways,
resulting in these chronic lung infections with these environmental bacteria. We propose a case-control
study comparing women with stable or resolved NTM disease with community-based age-matched
control subject with no history of respiratory disease, with a nested intervention trial in the subjects
with NTM disease. Our first aim is to compare body composition and general muscle strength in the
two groups. Our second aim is to compare lung function and cough physiology in the two groups, and
our third aim is to compare the two groups regarding their nutritional status and dietary intake. Our
fourth aim is to compare the health-related quality of life between the two groups, and in particular, to
assess the role of cough on the expected decreases quality of life in the NTM group. Our fifth and last
aim is to assess the effectiveness of expiratory muscle strength training (EMST) in the women with
NTM disease, using a sham-training device as a control intervention. If this simple, novel intervention
improves expiratory muscle strength and cough physiology as expected, we will then use these data to
support the submission of a proposal for a large clinical trial to determine if EMST can prevent
recurrent lung infections in these elderly women who are often disabled by this chronic lung disease.
Project Title: Epigenetic model of accelerated late life obesity and decline in muscle quality
Project Leader: Philip Scarpace
Obesity, including age-related obesity has become a national problem (1). Age-related obesity is a
major link to insulin resistance, diabetes, increased cardiac risk, atherosclerosis, and stroke, ultimately
leading to impaired physical performance and disability (2). Obesity in males and females over 70
years of age dramatically increases by nearly two-fold the number of remaining years spent disabled
(3). There are several potential causes of obesity, including genetic and epigenetic factors, as well as
lifestyle factors (6). A relatively small number of preclinical (mostly rodent) studies have examined the
role of maternal obesity on the susceptibility of offspring to develop obesity. Most have studied the
offspring at a young age, but the implications of the maternal environment for later life susceptibility to
dietary obesity remain unexplored. Aging is associated with a number of factors that may contribute to
a decline in physical performance with age (4), two of which are obesity and a decline in muscle
quality, and these may be interdependent as HF-feeding contributes to a decline in muscle function (Fig
5). We discovered that with increasing age, rats demonstrate a greater susceptibility to high fat (HF)
diet-induced weight gain and this is related to the presence of leptin resistance (5). Our umbrella
hypothesis is that maternal HF-induced obesity predisposes the offspring to accelerated age-related
dietary obesity and the associated decline in muscle quality. Put simply, at every age, offspring from
obese dams will demonstrate greater susceptibility to diet-induced obesity (DIO) than corresponding
offspring from lean dams, and this will accelerate the age-related decline in muscle quality leading to
loss of physical function at an early age. The underlying mechanisms are hypothesized to be maternal
leptin resistance hastens the onset of age-related leptin resistance in offspring, thus increasing the
susceptibility to DIO.
Project Title: A Network Based Analysis of Systemic Inflammation
Project Leader: Paul Borsa, PhD
This exploratory study will examine the temporal response of gene expression in the innate immune
system following acute muscle injury. In this exploratory project we will evaluate with newly
developed micro-array technology the gene expression of inflammation biology in low functioning and
high functioning old age-matched subjects in response to acute muscle injury (pre and 24-hours postinjury). We will use a novel technology that combines genomics, statistics and precise signaling
transduction pathways of inflammation, which will allow us to visualize and understand the complexity
of the inflammation responses and may provide us with additional biomarkers to monitor inflammation
in humans. We will correlate biomarkers of inflammation (gene expression) with measures of muscle
function (ROM, strength) to evaluate the inflammatory response and rate of recovery between subjects.
This exploratory study will generate pilot data that will be used to determine variances and effect sizes
for sample size calculations for a future large-scale clinical study.
Project Title: ACE inhibition and muscle quality
Project Leader: Christy Carter, PhD
This exploratory project is designed to use a rodent model of age-related physical decline to conduct
Preclinical testing of two pharmacologic interventions with the potential to forestall age-associated
physical decline: angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers
(ARB), and to study pathophysiologic changes postulated to play important roles in disability. In this
Exploratory Study we will assess this relationship by cross-sectionally assessing long-term ACEi and
ARB treatment in aged F344xBN male rats (24 to 30 months of age) and the impact on oxidative stress
(carbonyl proteins), inflammation (TNF-α IL-6) and apoptosis (caspases). We have observed that high
does ACEi treatment attenuates apoptotic signaling in skeletal muscle. Carter’s award of a translational
supplement to her R01 ACE inhibition and physical performance in aged rats is addressing mechanistic
hypotheses associated with this finding and several papers are currently in submission.
Project Title: Feasibility of Computer Adaptive Testing in Elders
Project Leader: Craig Velozo, PhD
One of the most promising areas of outcome measurements in healthcare is the use of computer
adaptive testing (CAT). CAT tailors the testing situation to individual respondent, to achieve a
combined efficiency and precision unattainable with traditional paper-and-pencil test. Several CAT
studies have shown promising psychometrics with administration of as few as 6 items in per construct.
In addition, Velozo and colleagues have developed a computer adaptive test, the ICF Activity Measure,
with an underlying extensive item bank (264 items) designed to measure physical function for
individuals with disabilities. The ICF measure has the potential to provide an efficient and precise
measure of physical functioning outcomes for sarcopenia interventions in the older adults. However,
the feasibility of CAT with the older adults is questionable. Some characteristics of the older adult
population, such as visual deficits and unfamiliarity/unease with technology may affect the feasibility
of CAT with this population.
Project Title: Leptin Inhibition, Blood Flow and Sarcopenia
Project Leader: Nihal Tümer, PhD
This exploratory study will test the hypothesis that inhibition of leptin signaling in obese rats would
lead to a decreased sympathetic nervous activity, improved vascular function and reduced blood
pressure without significantly affecting the already reduced metabolic effects of leptin. In the proposed
studies, lean young and obese senescent F-344xBN rats will be treated peripherally with this leptin
antagonist. Arterial blood pressure and heart rate will be followed with radiotelemetry and vascular
reactivity will be assessed at the end of the treatment period in vitro using isolated skeletal muscle
arteries. We will examine the responsiveness of the arteries to changes in intraluminal pressure and to
several vasoactive substances mediating endothelium-dependent and independent dilator responses.
Project Title: Autophagy and Sarcopenia in a Transgenic Mouse Model
Project Leader: Stephanie Woghlemuth, PhD
This pilot study is designed to investigate the extent and correlation of autophagy, sarcopenia and
decline in physical performance with age. We hypothesize that the incidence of sarcopenia and decline
in physical performance is associated with a decrease in autophagy and a consequential increase in
abnormal mitochondria. We will test our hypothesis in a prematurely aging transgenic mouse model
that specifically accumulates mitochondrial DNA mutations, reflecting age-related mitochondrial
damage. Our hypothesis will be assessed using the following specific aims: 1. Determine correlation
between decreased physical function and incidence of sarcopenia in new aging model. 2. Determine
age-related differences in autophagy in skeletal muscle of this new aging model. 3. Explore the
correlation between the incidence of sarcopenia and the decrease in autophagy and physical function.
The long-term goal of this study is to elucidate the cellular and molecular mechanisms of autophagy, its
role in age-related decline in skeletal muscle performance and disablement process, and to investigate
possible interventions for prevention and rehabilitation of disability.
Project Title: Acute Responses to Blood Flow Restricted Exercise
Project Leader: Todd Manini, PhD
There is a fundamental gap to understanding the ability to promote muscle function (mass, strength and
endurance) without high mechanical loading. The long-term goal is to develop a safe and effective
intervention without excessive tissue strain that increases muscle function. This project’s objective is
to determine the acute neuroendocrine and hemostatic responses to a novel approach for promoting
muscle function involving low-intensity exercise with blood flow restriction (BFRExercise). The
central hypothesis is that BFRExercise is a safe intervention that acutely upregulates growth factors
(i.e. serum growth hormone). The rationale for this study is that rehabilitation protocols involving
high-intensity exercise are not tolerated well by some individuals (i.e. elderly), can’t be performed by
some (i.e. Parkisonian patients), and is contraindicated for others (i.e. post-injury/surgery); thus, the
development of low-strain interventions to increase muscle function would dramatically change the
fields of neurologic, geriatric, orthopedic and rehabilitation medicine. This hypothesis will be tested by
pursuing 2 specific aims: 1) To compare acute neuroendocrine and hemostatic responses to BFR
exercise in young and old adults; 2) To compare acute neuroendocrine and hemostatic responses to
BFR exercise in Parkinsonian patients and healthy older adults. We will also pursue an exploratory
aim; 3) to evaluate the hemodynamic and inflammatory changes as a result of BFRexercise. This
research is significant because it is expected to result in the development of a novel, safe and practical
intervention that promotes muscle function in the absence of high-intensity exercise that will enhance
overall health and physical function in numerous populations.
Resveratrol for Reduced Muscle Lipid Content in Older Adults/ Resveratrol for Improved
performance: The RIPE Trial
Project Leaders: Todd Manini, PhD/ Stephen D. Anton
In this project, we aim to conduct a double-blind randomized placebo controlled pilot study to
determine whether resveratrol, a dietary ingredient, supplementation improves memory and physical
performance in older adults. Loss in memory and physical performance is a frequent complaint in
older adults and a growing public health issue. Additionally, later adulthood is associated with a
normative decline in both working and primary memory as well as domains including attention, speed
of processing and executive function. A key link to these processes may be related to the deleterious
effects of oxidative stress and chronic inflammation.
Dose-Response Effects of Weight Loss on Systemic Levels of Inflammation and Oxidative Stress
Project Leader: Stephen Anton, PhD
Obesity is associated with an elevated levels of inflammation and oxidative stress that may contribute
to muscle loss (sarcopenia), declines in physical functioning, and physical impairments in older adults.
Lifestyle interventions targeting weight loss through reductions in caloric intake and increased physical
activity may reduce systemic levels of inflammation and oxidative stress and thereby improve physical
functioning in obese, older adults. However, the mechanisms by which weight change and exercise
influence physical functioning and muscle loss remain largely understudied. Work in basic science
suggests that weight loss and exercise may avert sarcopenia by reducing inflammation, oxidative
damage, and the consequent atrophy and apoptosis (programmed cell death) of skeletal muscle
myocites. Thus, studies are needed to investigate the potential molecular links between obesity, weight
loss, and systemic levels of inflammation and oxidative stress. Findings from these studies may
identify novel therapeutic targets and therapies for improving health and decreasing the incidence of
age-related diseases associated with obesity and sarcopenia. The proposed study will utilize a large
sample of obese, older adults (N = 100) from rural communities to examine: 1) the dose response
relation between weight loss programs of varying intensity on changes in markers of systemic
inflammation (i.e., CRP, IL-6, and TNF-alpha), oxidative stress levels (i.e., oxLDL, myloperoxidase),
and vascular inflammation (E-selectin, VCAM-1) over six months, and 2) whether weight loss versus
changes in physical activity are related to improvements in biomarkers of inflammation and oxidative
stress, as well as physical function. Rural adults represent an ideal population to examine these
relationships since they have higher rates of obesity and obesity related comorbidities than urban
adults. The proposed study will take advantage of a large-scale NIH funded weight loss trial; thus,
all measurements can be completed in a cost-effective and timely manner.
The Role of Heat Shock Protein 70 Overexpression on the Recovery of Muscle Mass and
Function Following Cast Immobilization
Project Leader: Andrew Judge, PhD
The elderly often encounter more, and extended, periods of skeletal muscle disuse, such as bed rest or
cast immobilization, due to an increased likelihood of falls, disease and surgery. During these periods
of disuse significant muscle atrophy occurs, which may be exaggerated in the elderly compared to
young. Furthermore, during recovery following disuse, or reloading, muscles from the elderly fail to
recover mass and function. These combined effects of muscle atrophy and the inability of old muscle to
regrow leads to a significant loss of functional independence in the elderly. The central hypothesis of
the proposed work is that overexpression of Hsp70 will promote skeletal muscle regrowth and
improved function in old animals following a period of muscle disuse. The rationale for the proposed
work is based on the role that Hsp70 may play in enhancing protein synthesis and activating satellite
cells. Furthermore, muscles from adult rats increase Hsp70 expression during reloading and completely
regrow, whereas the ability of muscles from old rats to increase Hsp70 is significantly compromised.
To test this central hypothesis, we cast immobilized rats for 10 days to cause significant skeletal muscle
atrophy and then used gene transfer to overexpress Hsp70 in the soleus muscle of one limb, with the
contralateral limb serving as a control. Hsp70 overexpression significantly enhanced skeletal muscle
fiber regrowth in old rats. In a separate group of rats we tested “physical performance” via incline
plane and a swim test prior to cast immobilization, immediately following 10 days of cast
immobilization, and following 10 days of cast immobilization plus 10 days of reloading.
Overexpression of Hsp70 increased the mean time to failure on the incline plane test in old rats but not
young rats and increased the swim distance during repeated swim trials in young rats but not old rats.
Ongoing biochemical analyses will determine whether Hsp70 overexpression enhances markers of
protein synthesis and/or satellite cell activation during muscle regrowth.
Biological Effect of Weight Loss and Exercise in Elders
Project Leader: Stephen D. Anton, PhD
This study will lay the groundwork for a randomized controlled trial (RCT) of the effects of weight loss
plus exercise (WL+E) on inflammation, oxidative stress, apoptosis, body composition, intramuscular
fat, sarcopenia, muscle strength, and physical functioning in obese older adults.
Physical Exercise to Prevent Disability Pilot Study (The LIFE Study)
Project Leader: Marco Pahor, MD
To refine key trial design benchmarks (including sample size calculations to demonstrate the feasibility
of a full-scale trial and refining/developing recruitment, procedures, materials and organizational
infrastructure), the LIFE (Lifestyle Interventions for Independence in Elders) study conducted a pilot,
single-blind randomized, controlled trial involving comparison of a physical activity program of
moderate intensity to a successful aging program. A total of 400 sedentary persons aged 70-<90 years
who are at risk of disability were followed for at least one year at four intervention sites: Wake Forest
University School of Medicine in Winston Salem, NC, the University of Pittsburgh, Pittsburgh, PA, the
Cooper Institute in Dallas, TX, and the Stanford University in Palo Alto, CA. The Administrative
Coordinating Center and the Data Management and Quality Control Center are at Wake Forest
University School of Medicine. The LIFE study assessed the combined outcome of major mobility
disability defined as the incapacity to walk 400 m, or death, which will be the primary outcome of the
full-scale study. This outcome has not been used in previous randomized, controlled trials, and
therefore, a pilot study is needed to assess its incidence rate. Secondary outcomes include ADL
disability, major fall injuries and cardiovascular events. LIFE explored the effects of the intervention
on physical performance measures, cognitive function, health-related quality of life, and use of health
care services. In addition, LIFE explored and performed cost-effectiveness analyses of the intervention.
This pilot study will yield the necessary preliminary data to design a definitive Phase 3 randomized,
controlled trial. By providing a conclusive answer regarding whether physical activity is effective for
preventing major mobility disability or death, the results of the full-scale trial will have relevant
clinical and public health implications, and will fill an important gap in knowledge for practicing
evidence-based geriatric medicine. Study is complete. Secondary analyses are in progress. Phase 3
clinical trial has been awarded.
Testosterone Trial IVR Pilot
Project Leader: Marco Pahor, MD
The purpose of the study was to learn about the use of questionnaires about general health and feelings
of well-being in men who are > 65 years old, using a telephone system called Interactive Voice
Response (IVR). Questionnaires used in this study were the Harbor-UCLA 7-day diary and the
FACIT-Fatigue Scale. The study compared answers to questions collected on the phone system to those
that are written on paper forms to evaluate whether the IVR phone is an accurate and reliable way to
collect data. Information learned in this study will help to develop a study of testosterone use in men >
65 years old and the effects various aspects of their lives.
Testosterone Trial IVR Pilot #2
Project Leader: Marco Pahor, MD
The purpose of the study is to learn about the use of questionnaires about general health and feelings of
well-being in men who are > 65 years old, using a telephone system called Interactive Voice Response
(IVR). Questionnaires used in this study are the Positive and Negative Affect Scale (PANAS), SF-36
vitality subscale, and the PHQ-9. The study will compare answers to questions collected on the phone
system to those that are written on paper forms to evaluate whether the IVR phone is an accurate and
reliable way to collect data. Information learned in this study will help to develop a study of
testosterone use in men > 65 years old and the effects various aspects of their lives.
Chemotherapy, Weakness, Fatigue and Functional Limitation in Older Breast Cancer Survivors
Project Leader: Todd Manini, PhD
Women over the age of 65 years diagnosed with breast cancer will increase by 72% in the next 20
years2. As the effectiveness of adjuvant chemotherapy increases, it will become increasingly
recommended to older adults. Yet survivorship studies have primarily focused on young adults,
neglecting older women who are now the largest proportion of breast cancer survivors. Functional
dependence is a key determinant of poor quality of life, and a major source of health care and social
costs. In this project, we will study the biological and physiological characteristics of elderly breast
cancer survivors with expertise from a UF’s Institute on Aging with expertise on muscular aging and
functional decline. This collaboration is a unique breakthrough opportunity for identifying
interventions that will help to initiate programs to prevent or rehabilitate the long-term functional
impact of chemotherapy in the elderly. Beyond the effects found in breast cancer survivors, this project
has a potential for benefiting patients undergoing chemotherapy for any type of cancer. Therefore, this
will be the first step in a research pathway studying the long-term biological, functional, psychosocial,
geriatric and oncologic events that occur in older women surviving breast cancer, with potential for
designing several novel interventions.
Myogenic and Proteolytic Regulators in Response to blood Flow Restricted Exercise
Project Leader: Todd Manini, PhD
The loss of muscle mass and strength due to aging is of serious concern as it can limit physical
performance and is thought to act as a common pathway leading to heightened risk for outright physical
disability. Therefore, identifying interventions that induce myogenesis while minimizing proteolysis are
of major importance for establishing functional independence in older persons. Our interdisciplinary
team that includes experts in basic science (Dr.’s Powers & Leeuwenburgh), clinical science (Dr.’s
Manini & Vincent), translational clinical science (Dr. Borst), and laboratory methods (Dr. Zhang) is
uniquely suited to assess myogenic and proteolytic regulators while also mentoring the PI on techniques
used to quantify gene expression. Restricting blood flow during exercise to elicit a muscle regulatory
response is contrary to traditional thinking, but a growing literature indicates that blood flow restriction
during low intensity exercise (i.e. 20% of maximal strength) is a potent stimulus for systemic growth
factors, muscle protein synthesis and even muscle hypertrophy. This finding is somewhat unusual
because high intensity exercise exceeding 70% of maximal strength is typically needed to yield this type
of response. The mechanisms are unknown, but residual metabolic byproducts from glycolysis are
enhanced during ischemia and may act to modulate gene expression in a similar way as high intensity
exercise. The objective of this project is first, to ask what are the myogenic responses to acute exercise
performed at 20% of maximal strength with blood flow restriction when compared to a control exercise
performed at 20% of maximal strength without blood flow restriction. Second, we want to investigate the
proteolytic responses to acute exercise performed with blood flow restriction when compared to control
exercise. Thus, we offer two hypotheses: Hypothesis #1: Acute resistance exercise performed at 20% of
maximal strength coupled with blood flow restriction will upregulate myogenic gene expression (muscle
IGF-1, Myogenin, MyoD, and Myostatin). Hypothesis #2: Acute resistance exercise performed at 20%
of maximal strength coupled with blood flow restriction will downregulate proteolytic gene expression
(Atrogin-1, MuRF-1, Caspase-3, and FOXO3A). This research is significant because it is expected to
result in the development of a novel and practical intervention that promotes muscle growth in the
absence of high-intensity exercise. However, prior to widespread use of this modality the first step is to
investigate an acute bout of exercise to evaluate the potential underlying responses that will help in
developing a conceptual model for the mechanisms of action. Once these data are available chronic low
intensity exercise coupled with blood flow restriction can be studied in older adults for enhancement of
skeletal muscle health in older adults at risk of muscle atrophy.
The Influence of Resistance Exercise on Physical Function Depression, Quality of Life, Muscle
Morphology and Bone Metabolism in Stroke Patients
Project Leader: Kevin Vincent, PhD
Stroke is associated with musculoskeletal adaptations that result in decreased bone mineral density
(BMD), impaired motor unit activity and muscle weakness. These changes result in an increased risk
of osteoporosis and fracture and are associated with impaired mobility and the reduced ability to
perform activities of daily living (ADL). Additionally, patients who have experienced a stroke have
increased rates of depression and reduced indices of self-efficacy compared to their age matched
counterparts. Resistance exercise (RX) has been demonstrated to be a safe and effective means to
improve physical function and endurance in many clinical populations including geriatric, congestive
heart failure, organ transplant, cardiac, and cancer patients. Additional benefits in these populations
include increased BMD, increased indices of self-efficacy, reduced indices of depression, and reduced
blood pressure responses to a given workload. The relative influence of RX on these variables has not
been fully characterized in stroke patients. Recently there have been concerns that RX may increase
central artery compliance. However, the data regarding the influence of RX on arterial compliance has
been inconsistent. Additionally, there is a theoretical concern that RX may increase spasticity in stroke
patients, but this has not been demonstrated in any of published studies uses RX in this population.
The primary aims of this investigation will be to examine the influence of 24 weeks of Rx on physical
function (motor assessment scale six minute waling test), muscle hypertrophy an muscle morphology
(b-mode ultrasound measures of hypertrophy, muscle biopsy for fiber typing), bone mineral density
(Dual S-Ray Absorptiometry) and bone turnover markers osteocalcin, alkaline phosphatase and Nlinked telopeptides) in patients who have experienced a stroke. Secondary aims will be to assess
psychological state [anxiety (State Trait Anxiety Scale), depression (Geriatric Depression Scale)],
quality of life (SF-36) spasticity (modified Ashwoth scale), an arterial stiffness (assessed by endothelial
function and the resistance vessel technique). Adults (n=30) who have experienced a stroke will be
recruited for this investigation. Participants will be randomly assigned to either an RX group (n=15) or
a standard care group (n=15). Criterion measures will be assessed at baseline and after the 24 weeks of
either RX or standard care. It is hypothesized that RX will result in improved physical function,
increased muscle strength and muscle mass increase or preserved BMD, reduced bone resorption
markers, and improved psychological state of the participant by attenuating anxiety and depression
more than standard care. We also hypothesize that RX will not result in increased spasticity or arterial
stiffness.
Reversal of Age-related Obesity by an Unexpected Synergy between Leptin and Seemingly
Negligible Voluntary Wheel Running
Project Leader: Alexandra Shapiro, MD
This proposal seeks a successful strategy to prevent diet-induced obesity and functional disability in
aged rats. To date, treatments for obesity have been largely ineffective; thus, novel approaches are
urgently needed to combat the increasing obesity epidemic, particularly among older populations
Leptin treatment exerts potent response in lean rodents, producing impressive weight and fat loss, but is
generally ineffective in both dietary obese young and rats with age-related obesity. This phenomenon,
known as leptin resistance constitutes a major obstacle in curtailing age- and diet-induced weight gain
and has limited the value of leptin as a therapeutic agent for treating obesity. However, treatments that
are able to mitigate or circumvent leptin resistance may provide a viable strategy to restore the
effectiveness of leptin in treating obesity. Our exciting new data that a surprising synergy between
voluntary wheel running (WR) and leptin (two otherwise ineffective treatments in dietary obese rats)
restores the effectiveness of leptin therapy. In particular, the combination of WR + leptin therapy was
found to reverse the trajectory of HF-induced weight gain in young-obese, otherwise leptin-resistance
rats. This synergy is not a direct result of the distance run in the leptin/WR group, because there was
correlation between WR and weight loss. It appears that the act of WR and not the distance synergized
with leptin. The study expanded on these recent preliminary data by examining if a novel treatment
(WR + leptin) prevents HF-induced weight gain and also improves body composition (lean to fat ratio)
in leptin resistant, aged-obese rats. In this project, the physiological responses to voluntary wheel
running alone and in combination with central leptin gene delivery compared with sedentary animals
with and without leptin gene therapy in 24-months old obese rats will be examined over a 4-week
period. Additionally, the mechanisms underlying the synergy will be investigated. Against the
backdrop of the increasing obesity epidemic among older adults, evidence continues to accumulate
documenting the deleterious effect of excess weight on health and physical function. To date,
treatments for obesity have been largely ineffective; thus, novel approaches are urgently needed to
combat the increasing obesity epidemic, particularly among older populations. Study is complete.
Paper is accepted in Gerontology.
Oxidative Damage, Inflammation and Physical Exercise
Project Leader: Marco Pahor, MD
The hypotheses of this study are that a moderate-intensity physical exercise program may a) reduce
inflammation and oxidative damage markers, and b) prevent age-related physical performance loss
through these decreases. We plan to a) measure myeloperoxidase, 8-iso-prostaglandin F2alpha, and 3nitrotyrosine in the LIFE study, and 2) explore whether high levels of these biomarkers predict
dropouts.
Project Title: Molecular Mechanisms of Skeletal Muscle Loss in HIV-infected Older Persons
Project Leader: Todd Manini, PhD
Successful medical therapy has greatly improved survival for HIV-infected adults and now ¼ of these
individuals are over the age of 50 years. Unfortunately, this population faces a difficult challenge, as
they will age with a disease associated with severe muscle wasting that will greatly affect their physical
function. These individuals will face the aging process at a lower physical capacity and are expected to
have elevated rates of disability. Minimizing the loss in muscle mass is at the forefront for reducing
physical disability in aging adults. This study will investigate the mechanisms of muscle loss in HIV
infected older adults. One of these mechanisms, cellular apoptosis, is a key target that holds promise
for explaining the underlying rapid muscle loss seen with HIV infection and aging. We aim to recruit
20 HIV-infected and 20 non-infected adults aged 55 to 99 years of age to undergo tests of physical
function, blood work and undergo a muscle tissue sample. Results from this pilot study will be used to
develop a research trajectory that begins to uncover the reasons for accelerated muscle loss in aging
HIV-infected individuals.
SECONDARY DATA ANALYSES
The OAIC Clinical Research Core supports an epidemiology of aging laboratory to coordinate and supervise the
secondary analysis of existing data sets.
Diabetes, Sarcopenia and Depression in Older Persons
Project Leader: Cinzia Maraldi, MD
This exploratory project used Health ABC analysis data to assess the associations between diabetes,
functional status, and depression. The following paper has resulted from the analysis:
Maraldi,C., Volpato,S., Penninx,B.W., Yaffe,K., Simonsick,E.M., Strotmeyer,E.S., Cesari,M.,
Kritchevsky,S.B., Perry,S., Ayonayon,H.N., and Pahor,M. (2007): Diabetes Mellitus, Glycemic
Control, and Incident Depressive Symptoms Among 70- to 79-Year-Old Persons: The Health, Aging,
and Body Composition Study. Arch Intern Med, 167:1137-1144.
Exercise, Depression and Older Adult Outcomes
Project Leader: Elena Andresen, PhD
Major depression and clinically relevant depressive symptoms decrease in middle and older age, but
increase in the oldest ages. Depression can be an important and debilitating aspect occurring
secondarily to chronic conditions and acute events. Penninx et al. (77) demonstrated that depressive
symptoms in older persons predict subsequent decline in physical performance. Depressive symptoms
have been linked to incident disability (78), increased risk of falls (79,80) and reduced health related
quality of life (HRQoL;(81)). While physical activity and exercise are important to ameliorate
depression, it is not clear that all individuals benefit equally from physical activity. Intriguing results
from an exercise intervention in stroke survivors (82) suggest that improvements in HRQoL are
modified by the presence of depressive symptoms. The present study will reexamine this finding in a
group of general older adults from a randomized trial of exercise, the Lifestyle Interventions and
Independence for Elders (LIFE) (External project Physical Exercise to Prevent Disability - LIFE Pilot
Study NIH U01 AG022376, PI Dr. Marco Pahor). The specific hypothesis of this small exploratory
study is that depression modifies the effect of exercise on outcomes: specifically that HRQoL will be
improved more among those with clinically relevant levels of depressive symptoms. Our secondary
hypothesis is that exercise will differentially improve functional outcomes among those with
depressive symptoms. We will test these hypotheses cross-sectionally and in the one-year follow-up
data of the LIFE study. LIFE is a pilot, single-blind randomized controlled trial (n=424) comparing a
moderate intensity exercise program to a health education control in sedentary persons aged 70-90
years. Measures include the Quality of Well-Being (QWB), a continuous preference-based measure of
HRQoL (83); clinically relevant levels of depressive symptoms based on the Center for Epidemiologic
Studies Depression scale (CESD; (84)) &ge; 16 points; and functional measures include the Short
Physical Performance Battery, 4-meter walking speed, hand grip strength, and functional status (Basic
and Instrumental Activities of Daily Living (16). The sample size is sufficient to detect a moderately
strong interaction effect for depression and exercise intervention on the outcome of HRQoL. Effects on
functional outcomes will form the basis for developing more precise estimates in future intervention
studies. This secondary data analysis project will be performed by Drs. Elena Andresen, PhD (PI), and
Matteo Cesari, MD, PhD, with the support of the Clinical Research Core, and also in collaboration with
the Biostatistics and Data Management Core.
The results of this data analysis project are currently in preparation.
What is a meaningful change in physical performance? Findings from a clinical trial in older
adults (The LIFE-P Study)
Project Leader: Sooyeon Kwon, PhD
Performance measures provide important information, but the meaning of change in these measures is
not well known. Data from the LIFE-P study, a large, single blind clinical trial was used to 1) examine
the consistency of relationships between self-report and performance between groups; 2) estimate the
magnitude of meaningful change in 400-meter walk time (400MWT), 4-meter gait speed (4MGS), and
Short Physical Performance Battery (SPPB) and 3) evaluate the effect of direction of change on
estimates of magnitude.
One paper has been submitted and one paper published.
Risk factor for negative health-related events in older persons
Project Leaders: Marco Pahor, MD; Matteo Cesari, MD, PhD
This study uses data from several databases to evaluate:
a) Fatigue and mortality (InCHIANTI study)
b) Fatigue and physical function (InCHIANTI study)
c) Inflammatory markers and lipids (ilSirente study)
d) Mortality of self-assessed health status and physical performance (ilSirente study)
e) ACE-inhibition and biomarkers (TRAIN study)
f) Sarcopenia and mortality (InCHIANTI study)
g) Inflammatory and oxidative stress markers (TRAIN)
h) Physical performance and health events (HABC)
Two papers are under review, one book chapter submitted, and 20 papers have been published (see
publication list).
Epidemiology of Energy Expenditure and Health Outcomes in the Health ABC Study
Project Leader: Todd Manini, PhD
This project uses data from a cohort of the Health, Aging and Body Composition Study to determine
the role of energy expenditure in health related outcomes of the elderly.
One paper in press, one paper under review, two papers published (see publication list).
LIFE Obesity and Physical Performance Following Chronic Exercise Training
Project Leader: Todd Manini, PhD
This project uses data from the LIFE Pilot Study to evaluate the change in 400M walk and SPPB
stratified by obesity categories among older adults undergoing 12 months of physical exercise.
The results of this project were presented in an abstract at the 2007 Annual Meeting of the Gerontology
Society of America. One paper published (see publication list).
Health Literacy and knee arthroplasty in older adults
Project Leader: Miho Bautista, MD, BS
Health literacy has emerged as an important marker of healthcare outcomes. However, evidence
regarding the role of health literacy in the incidence of knee replacement surgery is not well known.
This study seeks to investigate the role of health literacy in the effect of education on knee replacement
surgery. Health literacy will be employed as a cognitive process that mediates the effect of education
on knee replacement surgery.
One paper submitted and one in preparation.
Specialized assessments within the PreClinical Research Core are supporting the following funded
projects.
III.
CAREER DEVELOPMENT
Following are names of individuals who received Pepper pilot funding and the funding received
subsequent to Pepper pilot funding.
PILOT AND EXPLORATORY STUDIES
1. A network based analysis of systematic inflammation (Borsa)
2. ACE inhibition and muscle quality (Carter)
3. Feasibility of computer adaptive testing in elders (Velozo)
Grants awarded or progress
NIH RO1AR055899, George PI
NIH RO1AG024526 supplement and VA contract, Carter
PI
Shepherd Center, Seel PI, NIH U01AR057967, Shulman
PI
4. Leptin inhibition, blood flow and sarcopenia (Tumer)
American Heart, Erdos PI, VA Tumer PI
5. Autophagy and sarcopenia in a transgenic mouse model
(Wohlgemuth)
NIH RC2AG036594, Cummings PI
6. Acute responses to blood flow restricted exercise (Manini)
7. Resveratrol for reduced muscle lipid content in older adults
(Anton/Manini)
8. Dose-Response Effects of Weight Loss on Systemic Levels of
Inflammation and Oxidative Stress (Anton)
OAIC Pilot, P30AG028740, Pahor PI
State of Florida (LBR) and NIH R21AG031974, Manini
PI
Study in progress, 50% recruitment complete
Study in progress, IRB approved, data collection is in
process
9. The role of heat shock protein 70 overexpression on the
recovery of muscle mass and function following cast
immobilization in old rats (Judge)
James and Esther King Biomedical Research Program,
Judge PI
NIH RO3AR056418-01A1, Judge PI
Bankhead-Coley Cancer Research Program, Judge PI
NIH K23AT004251 Award, Anton, PI
10. Biological effects of weight loss and exercise in elders
(Perri/Anton)
NIH R18L087800 Perri PI, American Heart, Anton PI
Thomas Maren Junior Investigator Award, Anton PI
McKnight Research Foundation, Anton/Manini PI
OAIC Pilot P30AG028740, Shapiro PI
NIH U01AG022376, Pahor PI
11. Physical exercise to prevent disability pilot study (Pahor)
NIH R01AG027529, Nicklas PI
NIH Supplement U01AG022376-05A2, Pahor PI
12. and 13. Testosterone Trial Interactive Voice Response (IVR)
Pilot #1 and #2 (Pahor)
14. Chemotherapy, weakness, fatigue and functional limitation in
older breast cancer survivors (Manini)
15. Resveratrol for improved memory: the RIPE trial
(Anton/Manini)
NIH U01AG030644, Snyder PI, Nayfield Field Center PI
Study in progress, IRB approved, data collection is in
process
McKnight Brain Research Foundation, Anton, Manini PI
16. Myogenic and Proteolytic Regulators in Blood Flow Restricted
Exercise (Manini)
Enrollment is complete, assays and data analyses are in
progress, grant resubmitting NIH R03AG032470, Manini
PI
17. The influence of resistance exercise on physical function,
depression, quality of life, muscle morphology and bone
metabolism in stroke patients (Vincent)
NIH R03AR059786, State of Florida, Foundation for
Physical Medicine and Rehabilitation, Vincent PI
18. Reversal of age-related obesity by synergy of leptin and
negligible wheel running (Shapiro)
Paper published, study complete, grants pending NIH
R01DK091710, Scarpace PI
American Heart, Shapiro PI
19. Molecular mechanisms of skeletal muscle loss in HIV-infected
older persons (Manini)
Enrollment 80% complete, grant in preparation
Underlined names denote junior/affiliated scholars
IV.
PUBLICATIONS
2010
1) Adkisson,EJ, Casey,DP, Beck,DT, Gurovich,AN, Martin,JS, Braith,RW: Central, peripheral and
resistance arterial reactivity: fluctuates during the phases of the menstrual cycle. Exp Biol Med
(Maywood ) 235:111-118, 2010
2) Aenlle,KK, Foster,TC: Aging alters the expression of genes for neuroprotection and synaptic function
following acute estradiol treatment. Hippocampus 20:1047-1060, 2010
3) Aiken Morgan,AT, Marsiske,M, Dzierzewski,JM, Jones,RN, Whitfield,KE, Johnson,KE, Cresci,MK:
Race-Related Cognitive Test Bias in the Active Study: A Mimic Model Approach. Exp Aging Res
36:426-452, 2010
4) Anton,SD, Martin,CK, Han,H, coulon,S, Cefalu,WT, Geiselman,P, Williamson,DA: Effects of stevia,
aspartame, and sucrose on food intake, satiety, and postprandial glucose and insulin levels. Appetite
55:37-43, 2010
5) Beavers,KM, Hsu,FC, Isom,S, Kritchevsky,SB, Church,T, Goodpaster,B, Pahor,M, Nicklas,BJ: LongTerm Physical Activity and Inflammatory Biomarkers in Older Adults. Med Sci Sports Exerc 2010
6) Befort,CA, Donnelly,JE, Sullivan,DK, Ellerbeck,EF, Perri,MG: Group versus individual phone-based
obesity treatment for rural women. Eat Behav 11:11-17, 2010
7) Bodhinathan,K, Kumar,A, Foster,TC: Intracellular redox state alters NMDA receptor response during
aging through Ca+/Calmodulin-dependent protein kinase II. J Neuroscience 30:1924, 2010
8) Botts,C, Daniels,MJ: A flexible approach to Bayesian multiple curve fitting. Comp Stat Data Analysis
52:5100-5120, 2010
9) Bouldin,ED, Winter,KH, Andresen,EM: Lack of choice in caregiving decision and caregiver risk of
stress, North Carolina, 2005. Prev Chronic Dis 7:A41, 2010
10) Bowden,MG, Clark,DJ, Kautz,SA: Evaluation of abnormal synergy patterns poststroke: relationship
of the Fugl-Meyer Assessment to hemiparetic locomotion. Neurorehabil Neural Repair 24:328-337,
2010
11) Brumback,BA, Bouldin,ED, Zheng,HW, Cannell,MB, Andresen,EM: Testing and Estimating
Model-Adjusted Effect-Measure Modification Using Marginal Structural Models and Complex
Survey Data. Am J Epidemiol 2010
12) Buford,TW, Anton,SD, Judge,AR, Marzetti,E, Wohlgemuth,SE, Carter,CS, Leeuwenburgh,C,
Pahor,M, Manini,TM: Models of accelerated sarcopenia: Critical pieces for solving the puzzle of
age-related muscle atrophy. Ageing Res Rev, 9(4):369-383, 2010
13) Buford,TW, Cooke,MB, Manini,TM, Leeuwenburgh,C, Willoughby,DS: Effects of age and
sedentary lifestyle on skeletal muscle NF-kappaB signaling in men. J Gerontol A Biol Sci Med Sci
65:532-537, 2010
14) Buford,TW, Manini,TM: Sedentary individuals as "controls" in human studies: the correct
approach? Proc Natl Acad Sci U S A 107:E134, 2010
15) Casey,DP, Nichols,WW, Conti,CR, Braith,RW: Relationship between endogenous concentrations of
vasoactive substances and measures of peripheral vasodilator function in patients with coronary
artery disease. Clin Exp Pharmacol Physiol 37:24-28, 2010
16) Castriotta,RJ, Eldadah,BA, Foster,WM, Halter,JB, Hazzard,WR, Kiley,JP, King,TE, Jr., Horne,FM,
Nayfield,SG, Reynolds,HY, Schmader,KE, Toews,GB, High,KP: Workshop on idiopathic
pulmonary fibrosis in older adults. Chest 138:693-703, 2010
17) Cesari,M, Pahor,M, Incalzi,RA: A key factor linking fibrinolysis and age-related subclinical and
clinical conditions. Cardiovasc Ther 63:752-759, 2010
18) Cesari,M, Pedone,C, Incalzi,RA, Pahor,M: ACE-inhibition and physical function: results from the
Trial of Angiotensin-Converting Enzyme Inhibition and Novel Cardiovascular Risk Factors
(TRAIN) study. J Am Med Dir Assoc 11:26-32, 2010
19) Cesari,M, Marzetti,E, Laudisio,A, Antonica,L, Pahor,M, Bernabei,R, Zuccala,G: Interaction of HDL
cholesterol concentrations on the relationship between physical function and inflammation in
community-dwelling older persons. Age Ageing 39:74-80, 2010
20) Cheng,J, Edwards,LJ, Maldonado-Molina,MM, Komro,KA, Muller,KE: Real longitudinal data
analysis for real people: building a good enough mixed model. Stat Med 29:504-520, 2010
21) Cheng,J, Qin,J, Zhang,B: Semiparametric estimation and inference for distributional and general
treatment effects. J Royal Stat Soc: Series B 71:881-904, 2010
22) Clark,BC, Manini,TM: Functional consequences of sarcopenia and dynapenia in the elderly. Curr
Opin Clin Nutr Metab Care 13:271-276, 2010
23) Clark,DJ, Ting,LH, Zajac,FE, Neptune,RR, Kautz,SA: Merging of healthy motor modules predicts
reduced locomotor performance and muscle coordination complexity post-stroke. J Neurophysiol
103:844-857, 2010
24) Classen,S, Winter,SM, Velozo,CA, Bedard,M, Lanford,DN, Brumback,B, Lutz,BJ: Item
development and validity testing for a self- and proxy report: the safe driving behavior measure. Am
J Occup Ther 64:296-305, 2010
25) Daniels,MJ, Wang,C: Discussion of "Missing Data in longitudinal studies: A review" by Ibrahim
and Molenberghs. Text 18:51-58, 2010
26) Dodd,SL, Gagnon,BJ, Senf,SM, Hain,BA, Judge,AR: Ros-mediated activation of NF-kappaB and
Foxo during muscle disuse. Muscle Nerve 41:110-113, 2010
27) Dutton,GR, Perri,MG, Stine,CC, Goble,M, Van,VN: Comparison of physician weight loss goals for
obese male and female patients. Prev Med 50:186-188, 2010
28) Dutton,GR, Perri,MG, ncer-Brown,M, Goble,M, Van,VN: Weight loss goals of patients in a health
maintenance organization. Eat Behav 11:74-78, 2010
29) Dutton,GR, Tan,F, Perri,MG, Stine,CC, ncer-Brown,M, Goble,M, Van,VN: What words should we
use when discussing excess weight? J Am Board Fam Med 23:606-613, 2010
30) Espeland,MA, Brunner,RL, Hogan,PE, Rapp,SR, Coker,LH, Legault,C, Granek,I, Resnick,SM:
Long-term effects of conjugated equine estrogen therapies on domain-specific cognitive function:
results from the Women's Health Initiative study of cognitive aging extension. J Am Geriatr Soc
58:1263-1271, 2010
31) Gine-Garriga,M, Guerra,M, Manini,TM, Mari-Dell'olmo,M, Pages,E, Unnithan,VB: Measuring
balance, lower extremity strength and gait in the elderly: construct validation of an instrument. Arch
Gerontol Geriatr 51:199-204, 2010
32) Giovannini,S, Cesari,M, Marzetti,E, Leeuwenburgh,C, Maggio,M, Pahor,M: Effects of ACEinhibition on IGF-1 and IGFBP-3 concentrations in older adults with high cardiovascular risk
profile. J Nutr Health Aging 14:457-460, 2010
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vasoactive substances and measures of peripheral vascular function in patients with coronary artery
disease.
147)
DeFries EL, Andresen EM: Cargiver health. In Aging in America: Psychological, physical, and
social issues. Westport, CT, Greenwood Publishing Group
148)
Green,M, Devine,D, Vierck,C, Yezierski,R: Effects of duloxetine on nociceptive reflexes and
operant measures of thermal sensitivity.
149)
Gurovich,AN, Beck,DT, Braith,RW: Aortic pulse wave analysis is not a surrogate for central
arterial pule wave velocity.
150)
Hain,BA, Dodd,SL, Judge,AR: IkBa degradation is necessary for muscle atrophy associated
with contractile claudication.
151)
Hall,AG, Bouldin,ED, Ali,A, Andresen,EM: Factors associated with residential stability and
caregiver employment among individuals with developmental disabilities living in the community.
152)
Harty,CM, Dupont,C, Chmielewski,TL, Mizner,RL: Inter-task comparison of frontal plane knee
position and movement in female athelets during three distinct movement tasks.
153)
Horner-Johnson,W, Suzuki,R, Krahn,GL, Andresen,EM, Drum,C: The structure of healthrelated quality of life in US populations: people with and without functional limitations.
154)
Howe,KS, Long,JH, Wronski,TJ, Turner,RT, Braith,RW: Skeletal effects of teriparatide in a
mouse model of glucocorticoid therapy.
155)
Jinze X, Knutson MD, Carter C, Leeuwenburgh,C: Calorie restriction attenuates the age-related
iron accumulation in skeletal muscle and improves grip strength.
156)
Joseph,AM, Hood,DA: TOM complex assembly in skeletal muscle mtiochondria-divergent
adaptive responses in different subcellular regions.
157)
Kim,JM, Heo,HS, Lee,EK, Choi,J, Seo A., Yu,bP, Chung,HY, Carter,CS: Exploration of
oxidative stress-induced inflammatory mechanism by angiotensin II in aged rat kidney.
158)
Li,N, Daniels,MJ, Li,G, Elashoff,R: An Exploration of Fixed and Random Effects Selection for
Longitudinal Binary Outcomes in the Presence of Non-ignorable Dropout.
159)
Malmstrom,TK, Andresen,E, Wolinsky,F: Predictors and correlate of urinary and fecal
incontinence in middle-aged African-Americans.
160)
Manini,TM, Buford,TW, Lott,D, Vandenborne,K, Daniels,MJ, Knaggs,J, Patel,H, Pahor,M,
Perri,MG, Anton,SD: Lower extremity tissue composition in response to weight loss and exercise
among moderately functioning obese old women: A randomized trial.
161)
Manini,T, Cheng,J, Shorr,R, Pahor,M, Leeuwenburgh,C, Perri,M, Anton,S: Effects of a weight
loss plus exercise program on muscle composition in obese, older adult women.
162)
Manini,T, Kushang,P, Bauer,D, Ziv,E, Schoeller,D, Mackey,D, Li,R, Newman,A, Nalls,M,
Zmuda,J, Harris,T, H: European ancestry and resting metabolic rate.
163)
Neugaard B, Chumbler N, Schofield RS, Andresen EM, Lutz B, Brumback B: The
effectiveness of a VA heart failure care coordination/home telehealth program on health care
resources use and mortality.
164)
Picca,A, Fracasso,F, Pesce,V, Cantatore,P, Joseph,AM, Leeuwenburgh,CL, Gadaleta,MN,
Lezza,AM: Aging and clorie restriction differentially affect Mitochondrial Transcription Factor A
bidning to rat brain mitochondrial DNA inducing changes in mitochondrial DNA content.
165)
Radcliff,TA, Perri,MG, Durning,PE, Limacher,M, Janicke,DM, Lutes,LD, Daniels,MJ,
Martin,A: Cost Effectiveness of Telephone versus Face-to-Face Extended Care Programs for the
Management of Obesity in Rural Settings
166)
Rahim-Williams,B, Fillingim,R, Riley,J: A quantitative and qualitative review of ethnic group
differences in experimental pain sensitivity.
167)
Rahim-Williams,B, Riley,J: Ethnic group differences in arthritis pain and negative affect among
African Americans, Hispanics and non-Hispanic Whites.
168)
Rahim-Williams,B, Fillingim,RB, Riley,IJL: Characterizing ethnic group differences in
experimental pain: A review.
169)
Rauch,P, Treise,D, Price,Y, Shorr,RI: Baby boomers and health: Heart disease content in mass
circulation magazines, 1996-2000.
170)
Reed,SA, Senf,SM, Cornwell,AW, Kandarian,SC, Judge,AR: Co-inhibition of IKKa OR IKKb
and FOXO prevents skeletal muscle disuse atrophy.
171)
Riley,JR, III, Rahim-Williams,B, Zsembik,BA, Duncan,RP, Gilbert,GH, Heft,MW: Race/ethnic
and sex differences in self-care for pain: a substitute for formal health care services?
172)
Riley,JR, III, Rahim-Williams,B, Gibson,E: Sex and ethnic group differences in physical
functioning and pain as a predictor of depression among older adults with arthritis.
173)
Rossen,LM, Milson,VA, Ross,KM, Daniels,MJ, Nackers,LM, Perri,MG: Benefits and Risks of
Weight-loss Treatment for Elderly.
174)
Schootman,M, Andresen,EM, Wolinsky,FD: Association of adverse housing and neighborhood
conditions with inflammatory markers among middle-aged African Americans.
175)
Senf,SM, Dodd,S, Hain,B, Judge,AR: Hsp70 regulates Foxo3a DNA-binding and
transcriptional activation of atrogin-1 through an Akt-independent mechanism: A nuclear event?
176)
Senf,SM, Sandesara,PB, Reed,SA, Judge,AR: p300 Acetyltransferase activity is necessary and
sufficient to repress FOXO signaling in skeletal muscle.
177)
Shapiro,A, Gao,Y, Cheng,K, Scarpcae,P: Prevention and reversal of diet-induced leptin
resistance and obesity with a sugar-free diet despite high fat content.
178)
Shorr,RI, Chandler,AM, Mion,LC, Waters,TM, Daniels,MJ, Kessler,LA, Miller,ST:
Effectiveness of a proximity alarm system to prevent falls in hospitalized patients.
179)
Uphold,C, Stahl,C, Reid,K, Freytes,M: Investigating longitudinal difference in tobacco use,
stress, coping and depression in men with HIV infection.
180)
Wang,C, Daniels,MJ: A Note on MAR, Identifying Restrictions, and Sensitivity Analysis in
Pattern Mixture Models With and Without Covariates for Incomplete Data.
181)
Weaver,NL, Alcaraz,KI, Andresen,EM: The neighborhood voice: Evaluating a mobile research
vehicle for recruiting African Americans to participate in cancer control studies.
182)
Wikstrom,EA, Tillman,MD, Borsa,PA: Sex-difference in neuromuscular control alter dynamic
postural stability.
183)
Wolinsky FD, Miller,DK, Andresen,EM: The dimensional structure of functional assessments.
184)
Yezierski,R, King,CMDCC, Vierck,C: Effects of age on thermal sensitivity.
185)
Yu,C-G, Yezierski,R, Joshi,A, Raza,K, Li,Y, Geddes,J: RNAi approach reveals a specific role
ERK2 in the deleterious consequences of spinal caord injury.
186)
Zeier,Z, Madorsky,I, Xu,Y, Ogle,W, Notterpek,L, Foster,T: Regionally specific gene
expression in the hippocampus: Effect of aging and caloric restriction.
Junior Scholars
Stephen D. Anton, PhD
Published/In Press
1) Anton,SD, Manini,TM: Does self-reported physical activity underestimate the importance of
activity in cardiovascular disease prevention? Curr Cardiol Rep, In Press
2) Anton,SD, Martin,CK, Han,H, coulon,S, Cefalu,WT, Geiselman,P, Williamson,DA: Effects of
stevia, aspartame, and sucrose on food intake, satiety, and postprandial glucose and insulin levels.
Appetite 55:37-43, 2010
3) Buford,TW, Anton,SD, Judge,AR, Marzetti,E, Wohlgemuth,SE, Carter,CS, Leeuwenburgh,C,
Pahor,M, Manini,TM: Models of accelerated sarcopenia: Critical pieces for solving the puzzle of
age-related muscle atrophy. Ageing Res Rev, 9(4):369-383, 2010
4) Chung,JH, Kim,M, Kim,DH, Anton,SD, Choi,JS, Park,KY, Rhee,SH, Yu,bP, Chung,HY: PPAR
expression by a short-term feeding of zingerone in aged rats. J Medicinal Food, In Press
5) Manini,TM, Newman,AB, Fielding,R, Blair,SN, Perri,MG, Anton,SD, Goodpaster,BC, Katula,JA,
Rejeski,WJ, Kritchevsky,SB, Hsu,FC, Pahor,M: Effects of exercise on mobility in obese and
nonobese older adults. Obesity (Silver Spring) 18:1168-1175, 2010
6) Martin CK, Stewart TM, Anton SD, Copeland AL, Williamson DA: Health Psychology. In Clinical
Psychology. Hersen M, Gross AM, Eds. New York, John Wiley & Sons, In Press
7) Newton,RL, Jr., Han,H, Anton,SD, Martin,CK, Stewart,TM, Lewis,L, Champagne,CM, Sothern,M,
Ryan,D, Williamson,DA: An environmental intervention to prevent excess weight gain in AfricanAmerican students: a pilot study. Am J Health Promot 24:340-343, 2010
8) Perri MG, Foreyt JP, Anton SD: Preventing weight gain after weight loss. In Handbook of Obesity
Treatment: Clinical Applications. 3rd ed. Bray GA, Bouchard C, Eds. New York, Marcel Dekkar,
Inc., In Press
9) Shapiro,A, Cheng,K, Gao,D, Seo,S, Anton,SD, Carter,CS, Zhang,Y, Scarpace,P, Tumer,N: The act
of voluntary wheel running reverses dietary hyperphagia and increases leptin signaling in ventral
tegmental area of aged dietary obese rats. J Gerontol, In Press
10) Williamson,DA, Anton,SD, Han,H, Champagne,CM, Allen,R, Leblanc,E, Ryan,DH, McManus,K,
Laranjo,N, Carey,VJ, Loria,CM, Bray,GA, Sacks,FM: Adherence is a multi-dimensional construct
in the POUNDS LOST trial. J Behav Med 33:35-46, 2010
11) Williamson,DA, Anton,SD, Han,H, Champagne,CM, Allen,R, Leblanc,E, Ryan,DH, Rood,J,
McManus,K, Laranjo,N, Carey,VJ, Loria,CM, Bray,GA, Sacks,FM: Early behavioral adherence
predicts short and long-term weight loss in the POUNDS LOST study. J Behav Med 33:305-314,
2010
12) Williamson, DA, Anton,SD, Han,H, Champagne,CM, Allen, R, LeBlanc, E, Ryan,DH,
McManus,K, Laranjo,N, Carey,VJ, Loria,CM, Bray,GA, Sacks,FM: Early behavioral adherence
(but not dietary adherence) Predicts Short and Long-Term Weight Loss in the POUNDS LOST
Trial. Annals of Behavior Medicine, In Press
13) Xu,J, Seo,AY, Vorobyeva,DA, Carter,CS, Anton,SD, Lezza,AM, Leeuwenburgh,C: Beneficial
effects of a Q-ter based nutritional mixture on functional performance, mitochondrial function, and
oxidative stress in rats. PLoS ONE 5:e10572, 2010
Under Review
1) Anton ,S, Manini,T, Milsom,V, Dubyak,P, Cesari,M, Marsiske,M, Cheng,J, Pahor,M,
Leeuwenburgh,C, Perri,M: Effects of a weight loss plus exercise program on physical functioning
in obese, older African-American and Caucasian women.
2) Anton,SD, Gallager,J, Carey,VJ, Laranjo,N, Cheng,J, Champagne,CM, Ryan,DH, McManus,K,
Loria,CM, Bray,GA, Sacks,FM, Williamson,DA: Effects of diet type on changes in food cravings
following weight loss: Findings from the POUNDS LOST trial.
3) Manini,TM, Buford,TW, Lott,D, Vandenborne,K, Daniels,MJ, Knaggs,J, Patel,H, Pahor,M,
Perri,MG, Anton,SD: Lower extremity tissue composition in response to weight loss and exercise
among moderately functioning obese old women: A randomized trial.
Miho Bautista, MD
Published/In Press
1) Peter C, Beyth R, Bautista M. The Geriatric Patient, In: Civetta, Taylor and Kirby’s Critical Care,
4th Edition. Lippincott Williams & Wilkins, Philidelphia, PA, In press
2) Stein,GH, Shibata,A, Bautista,MK: Webinar: free international distant real time interactive
tutoring. Med Teach 32:619-620, 2010
Under Review
1) Bautista,MK, Meuleman,J, Shorr,RI, Beyth,RJ: Students' career choice and evaluation of multimodal interdisciplinary care training in a geriatric clerkship.
Thomas W. Buford, PhD
Published/In Press
1) Buford,TW, Anton,SD, Judge,AR, Marzetti,E, Wohlgemuth,SE, Carter,CS, Leeuwenburgh,C,
Pahor,M, Manini,TM: Models of accelerated sarcopenia: Critical pieces for solving the puzzle of
age-related muscle atrophy. Ageing Res Rev, 9(4):369-383, 2010
2) Buford,TW, Cooke,MB, Manini,TM, Leeuwenburgh,C, Willoughby,DS: Effects of age and
sedentary lifestyle on skeletal muscle NF-kappaB signaling in men. J Gerontol A Biol Sci Med Sci
65:532-537, 2010
3) Buford,TW, Cooke,MB, Shelmadine,BD, Hudson,GM, Redd,LL, Willoughby,DS: Differential
gene expression of Fox01, ID1, and ID3 between young and older men and associations with
muscle mass and function. Aging Clin Exp Res, In Press
4) Buford,TW, Manini,TM: Sedentary individuals as "controls" in human studies: the correct
approach? Proc Natl Acad Sci U S A 107:E134, 2010
Under Review
1) Manini,TM, Buford,TW, Lott,D, Vandenborne,K, Daniels,MJ, Knaggs,J, Patel,H, Pahor,M,
Perri,MG, Anton,SD: Lower extremity tissue composition in response to weight loss and exercise
among moderately functioning obese old women: A randomized trial.
Andrew Judge, PhD
Published/In Press
1) Buford,TW, Anton,SD, Judge,AR, Marzetti,E, Wohlgemuth,SE, Carter,CS, Leeuwenburgh,C,
Pahor,M, Manini,TM: Models of accelerated sarcopenia: Critical pieces for solving the puzzle of
age-related muscle atrophy. Ageing Res Rev, 9(4):369-383, 2010
2) Dodd,SL, Gagnon,BJ, Senf,SM, Hain,BA, Judge,AR: Ros-mediated activation of NF-kappaB and
Foxo during muscle disuse. Muscle Nerve 41:110-113, 2010
3) McClung,JM, Judge,AR, Powers,SK, Yan,Z: p38 MAPK links oxidative stress to autophagyrelated gene expression in cachectic muscle wasting. Am J Physiol Cell Physiol 298:C542-C549,
2010
4) Senf,SM, Dodd,SL, Judge,AR: FOXO signaling is required for disuse muscle atrophy and is
directly regulated by Hsp70. Am J Physiol Cell Physiol 298:C38-C45, 2010
Under Review
1) Hain,BA, Dodd,SL, Judge,AR: IkBa degradation is necessary for muscle atrophy associated
with contractile claudication.
2) Reed,SA, Senf,SM, Cornwell,AW, Kandarian,SC, Judge,AR: Co-inhibition of IKKa OR IKKb
and FOXO prevents skeletal muscle disuse atrophy.
3) Senf,SM, Dodd,S, Hain,B, Judge,AR: Hsp70 regulates Foxo3a DNA-binding and
transcriptional activation of atrogin-1 through an Akt-independent mechanism: A nuclear
event?
4) Senf,SM, Sandesara,PB, Reed,SA, Judge,AR: p300 Acetyltransferase activity is necessary and
sufficient to repress FOXO signaling in skeletal muscle.
Todd Manini, PhD
Published/In Press
1) Anton,SD, Manini,TM: Does self-reported physical activity underestimate the importance of
activity in cardiovascular disease prevention? Curr Cardiol Rep, In Press
2) Buford,TW, Anton,SD, Judge,AR, Marzetti,E, Wohlgemuth,SE, Carter,CS, Leeuwenburgh,C,
Pahor,M, Manini,TM: Models of accelerated sarcopenia: Critical pieces for solving the puzzle of
age-related muscle atrophy. Ageing Res Rev, 9(4):369-383, 2010
3) Buford,TW, Cooke,MB, Manini,TM, Leeuwenburgh,C, Willoughby,DS: Effects of age and
sedentary lifestyle on skeletal muscle NF-kappaB signaling in men. J Gerontol A Biol Sci Med Sci
65:532-537, 2010
4) Buford,TW, Manini,TM: Sedentary individuals as "controls" in human studies: the correct
approach? Proc Natl Acad Sci U S A 107:E134, 2010
5) Chale-Rush,A, Guralnik,JM, Walkup,MP, Miller,ME, Rejeski,WJ, Katula,JA, King,AC,
Glynn,NW, Manini,TM, Blair,SN, Fielding,RA: Relationship Between Physical Functioning and
Physical Activity in the Lifestyle Interventions and Independence for Elders Pilot. J Am Geriatr
Soc, In Press
6) Clark,BC, Manini,TM: Functional consequences of sarcopenia and dynapenia in the elderly. Curr
Opin Clin Nutr Metab Care 13:271-276, 2010
7) Gine-Garriga,M, Guerra,M, Manini,TM, Mari-Dell'olmo,M, Pages,E, Unnithan,VB: Measuring
balance, lower extremity strength and gait in the elderly: construct validation of an instrument.
Arch Gerontol Geriatr 51:199-204, 2010
8) Manini,TM, Newman,AB, Fielding,R, Blair,SN, Perri,MG, Anton,SD, Goodpaster,BC, Katula,JA,
Rejeski,WJ, Kritchevsky,SB, Hsu,FC, Pahor,M: Effects of exercise on mobility in obese and
nonobese older adults. Obesity (Silver Spring) 18:1168-1175, 2010
9) Manini,TM, Vincent,KR, Leeuwenburgh,CL, Lees,HA, Kavazis,AN, Borst,SE, Clark,BC:
Myogenic and proteolytic mRNA expression following blood flow restricted exercise. In Press Acta
Physiol (Oxf)
Under Review
1) Anton ,S, Manini,T, Milsom,V, Dubyak,P, Cesari,M, Marsiske,M, Cheng,J, Pahor,M,
Leeuwenburgh,C, Perri,M: Effects of a weight loss plus exercise program on physical functioning
in obese, older African-American and Caucasian women.
2) Manini,TM, Buford,TW, Lott,D, Vandenborne,K, Daniels,MJ, Knaggs,J, Patel,H, Pahor,M,
Perri,MG, Anton,SD: Lower extremity tissue composition in response to weight loss and exercise
among moderately functioning obese old women: A randomized trial.
3) Manini,T, Cheng,J, Shorr,R, Pahor,M, Leeuwenburgh,C, Perri,M, Anton,S: Effects of a weight loss
plus exercise program on muscle composition in obese, older adult women.
4) Manini,T, Kushang,P, Bauer,D, Ziv,E, Schoeller,D, Mackey,D, Li,R, Newman,A, Nalls,M,
Zmuda,J, Harris,T, H: European ancestry and resting metabolic rate.
Emanuele Marzetti, MD, PhD
Published/In Press
1) Buford,TW, Anton,SD, Judge,AR, Marzetti,E, Wohlgemuth,SE, Carter,CS, Leeuwenburgh,C,
Pahor,M, Manini,TM: Models of accelerated sarcopenia: Critical pieces for solving the puzzle of
age-related muscle atrophy. Ageing Res Rev, 9(4):369-383, 2010
2) Cesari,M, Marzetti,E, Laudisio,A, Antonica,L, Pahor,M, Bernabei,R, Zuccala,G: Interaction of
HDL cholesterol concentrations on the relationship between physical function and inflammation in
community-dwelling older persons. Age Ageing 39:74-80, 2010
3) Giovannini,S, Cesari,M, Marzetti,E, Leeuwenburgh,C, Maggio,M, Pahor,M: Effects of ACEinhibition on IGF-1 and IGFBP-3 concentrations in older adults with high cardiovascular risk
profile. J Nutr Health Aging 14:457-460, 2010
4) Giovannini,S, Onder,G, Leeuwenburgh,C, Carter,C, Marzetti,E, Russo,A, Capoluongo,E, Pahor,M,
Bernabei,R, Landi,F: Myeloperoxidase levels and mortality in frail community-living elderly
individuals. J Gerontol A Biol Sci Med Sci 65:369-376, 2010
5) population-based study. Clin Rheumatol 28:145-151, 2009
6) Laudisio,A, Marzetti,E, Pagano,F, Bernabei,R, Zuccala,G: Masticatory dysfunction is associated
with worse functional ability: a population-based study. J Clin Periodontol 37:113-119, 2010
7) Marzetti,E, Hwang,JC, Lees,HA, Wohlgemuth,SE, Dupont-Versteegden,EE, Carter,CS,
Bernabei,R, Leeuwenburgh,C: Mitochondrial death effectors: relevance to sarcopenia and disuse
muscle atrophy. Biochim Biophys Acta 1800:235-244, 2010
8) Marzetti,E, Privitera,G, Simili,V, Wohlgemuth,SE, Aulisa,L, Pahor,M, Leeuwenburgh,C: Multiple
pathways to the same end: mechanisms of myonuclear apoptosis in sarcopenia of aging.
ScientificWorldJournal 10:340-9.:340-349, 2010
9) Wohlgemuth,SE, Seo,AY, Marzetti,E, Lees,HA, Leeuwenburgh,C: Skeletal muscle autophagy and
apoptosis during aging: effects of calorie restriction and life-long exercise. Exp Gerontol 45:138148, 2010
10) Xu,J, Marzetti,E, Seo,AY, Kim,JS, Prolla,TA, Leeuwenburgh,C: The emerging role of iron
dyshomeostasis in the mitochondrial decay of aging. Mech Ageing Dev 131:487-493, 2010
Under Review
1) Carter,CS, Giovannini,S, Seo A., Dupree,J, Morgan,D, Chung,HY, Lee,H, Daniel,M, Hubbard,G,
Lee,S, Ikeno,Y, Marzetti,E: Differential effects of enalapril and losartan on body composition and
indices of muscle quality in aged male Fischer 344 X Brown Norway rats.
Bridgett Rahim-Williams, PhD, MPH
Published/In Press
1) Rahim-Williams,B, Tomar,S, Blanchard,S, Riley III,JL: Influences of adult-onset diabetes on
orofacial pain and related health behaviors. In Press J Public Health Dent
2) Rahim-Williams,B: Beliefs, behaviors and modifications of Type 2 diabetes self-management
among African American Women. In Press J Natl Med Assoc
Under Review
1) Rahim-Williams,B, Fillingim,R, Riley,J: A quantitative and qualitative review of ethnic group
diffrences in experimental pain sensitivity.
2) Rahim-Williams,B, Riley,J: Ethnic group differences in arthritis pain and negative affect among
African Americans, Hispanics and non-Hispanic Whites.
3) Rahim-Williams,B, Fillingim,RB, Riley,IJL: Characterizing ethnic group differences in
experimental pain: A review.
4) Riley,JR, III, Rahim-Williams,B, Zsembik,BA, Duncan,RP, Gilbert,GH, Heft,MW: Race/ethnic
and sex differences in self-care for pain: a substitute for formal health care services?
5) Riley,JR, III, Rahim-Williams,B, Gibson,E: Sex and ethnic group differences in physical
functioning and pain as a predictor of depression among older adults with arthritis.
Kevin R. Vincent, MD
Published/In Press
1) Manini,TM, Vincent,KR, Leeuwenburgh,CL, Lees,HA, Kavazis,AN, Borst,SE, Clark,BC:
Myogenic and proteolytic mRNA expression following blood flow restricted exercise. Acta Physiol
(Oxf), In Press
2) Vincent,HK, Ben-David,K, Cendan,J, Vincent,KR, Lamb,KM, Stevenson,A: Effects of bariatric
surgery on joint pain: a review of emerging evidence. Surg Obes Relat Dis 6:451-460, 2010
3) Vincent,HK, Lamb,KM, Day,TI, Tillman,SM, Vincent,KR, George,SZ: Morbid obesity is
associated with fear of movement and lower quality of life in patients with knee pain-related
diagnoses. PM R 2:713-722, 2010
4) Vincent,HK, Omli,MR, Vincent,KR: Absence of combined effects of anemia and bilateral surgical
status on inpatient rehabilitation outcomes following total knee arthroplasty. Disabil Rehabil
32:207-215, 2010
5) Vincent,HK, Vincent,KR, Lamb,KM: Obesity and mobility disability in the older adult. Obes Rev
11:568-579, 2010
Stephanie Wohlgemuth, PhD
Published/In Press
1) Buford,TW, Anton,SD, Judge,AR, Marzetti,E, Wohlgemuth,SE, Carter,CS, Leeuwenburgh,C,
Pahor,M, Manini,TM: Models of accelerated sarcopenia: Critical pieces for solving the puzzle of
age-related muscle atrophy. Ageing Res Rev, 9(4):369-383, 2010
2) Marzetti,E, Hwang,JC, Lees,HA, Wohlgemuth,SE, Dupont-Versteegden,EE, Carter,CS,
Bernabei,R, Leeuwenburgh,C: Mitochondrial death effectors: relevance to sarcopenia and disuse
muscle atrophy. Biochim Biophys Acta 1800:235-244, 2010
3) Marzetti,E, Privitera,G, Simili,V, Wohlgemuth,SE, Aulisa,L, Pahor,M, Leeuwenburgh,C: Multiple
pathways to the same end: mechanisms of myonuclear apoptosis in sarcopenia of aging.
ScientificWorldJournal 10:340-349, 2010
4) Wohlgemuth,SE, Seo,AY, Marzetti,E, Lees,HA, Leeuwenburgh,C: Skeletal muscle autophagy and
apoptosis during aging: effects of calorie restriction and life-long exercise. Exp Gerontol 45:138148, 2010
University of Florida
Claude D. Pepper Older Americans Independence Center
Marco Pahor, M.D.
Lauren Crump, M.P.H.
Principal Investigator
Department of Aging and Geriatrics
College of Medicine
University of Florida
PO Box 100107
Gainesville, FL 32610
Phone: 352-265-7227 Fax: 352-265-7228
Email: [email protected]
Project Director
Department of Aging and Geriatrics
College of Medicine
University of Florida
PO Box 100107
Gainesville, FL 32610
Phone: 352-265-7227 Fax: 352-265-7228
Email: [email protected]
Recognition and Awards: Prize or honors, NOT grant awards, should be a listing of all major
scientific awards received by your center’s personnel in 2010.
Christiaan Leeuwenburgh, PhD
Exemplary Teacher Award, University of Florida College of Medicine, 2010
Kindal Sweet, Undergraduate Affiliated Scholar (Christy Carter, PhD, Primary Mentor)
Cluff Award for for Undergraduate Research in Aging at the University of Florida, 2010
University of Florida
Claude D. Pepper Older Americans Independence Center
Marco Pahor, M.D.
Lauren Crump, M.P.H.
Principal Investigator
Department of Aging and Geriatrics
College of Medicine
University of Florida
PO Box 100107
Gainesville, FL 32610
Phone: 352-265-7227 Fax: 352-265-7228
Email: [email protected]
Project Director
Department of Aging and Geriatrics
College of Medicine
University of Florida
PO Box 100107
Gainesville, FL 32610
Phone: 352-265-7227 Fax: 352-265-7228
Email: [email protected]
Minority Research: List activities with minority trainees and research focusing on hypotheses
dealing with minority health. Clinical research that has an expected number of minority subjects
(a NIH requirement) is NOT what is desired for this section. Only work that has a comparison of
minority members to majority members such as work on health disparities should be included.
Trainee:
Bridgett Rahim-Williams, PhD, MPH, MA
Claude D. Pepper Older Americans Independence Center (OAIC) Minority Supplement
Physical activity, pain and functional mobility amoung women
NIH P30AG028740-02S2
9/30/2008 – 3/31/2011
Goals:
--To acquire training and advanced scientific knowledge in interdisciplinary and translational
basic and clinical science research addressing health disparities associated with minority aging
and pain across the life span.
--To obtain training and advanced scientific knowledge in minority health disparities associated
with prevention and rehabilitation of disability in aging.
--To acquire advanced training and expertise in pain assessment that includes psychophysical
testing, clinical pain assessment, and innovative, technological interventions for the
rehabilitation of disability and improved performance in physical activity and functional mobility
outcomes amoung older adults.
--To gain practical and experiential education and training in research methods, advanced
biostatistical analyses, experimental design and grant writing to facilitate transition to an
independent investigator with exernally funded minority aging and pain research.
University of Maryland Baltimore
Claude D. Pepper Older Americans Independence Center
(UM-OAIC)
Andrew P. Goldberg, M.D.
Principal Investigator
Professor and Head, Division of Gerontology
Department of Medicine
Phone: 410-605-7183
FAX: 410-605-7116
[email protected]
Jay Magaziner, Ph.D., M.S.Hyg.
Co-Principal Investigator
Professor and Department Chair, Epidemiology and Preventive Medicine, Division Head, Gerontology
Department of Epidemiology
Phone: 410-706-3553
FAX: 410-706-4433
[email protected]
Kara Longo, M.S.
Health Program Manager
Phone: 410-605-7000 x 4804
FAX: 410-605-7913
[email protected]
Anne Sullens, M.A.
Coordinator
Phone: 410-605-7000 x 5425
FAX: 410-605-7913
[email protected]
Address Correspondence:
VA Medical Center, GRECC (BT/18/GR)
10 North Greene Street
Baltimore, MD 21201
I. CENTER DESCRIPTION
The mission of the University of Maryland Older Americans Independence Center (UM-OAIC) is exercise and
motor learning based rehabilitation research to optimize the recovery of older adults who have suffered a stroke,
hip fracture or other chronic debilitating disease, and translate these findings into effective community-based
rehabilitation programs. This will be accomplished through specific aims to : 1) conduct basic and clinical
research examining the mechanisms underlying functional disabilities associated with chronic diseases of aging
to characterize the functional impairments that define the disability phenotype across domains of neuromotor,
muscular, metabolic, cardiovascular and psychosocial function; 2) apply these scientific findings to design
novel exercise and motor learning-based rehabilitation strategies; 3) determine the mechanisms by which these
rehabilitation interventions improve functional and clinical outcomes in older people with functional
impairments; 4)translate efficacious rehabilitation strategies into community-based clinical studies; 5) support
Pilot Exploratory Studies Core (P/ESC) and Development Projects (DP’s) that study the mechanisms
underlying the disability phenotoype and functional and clinical responses to rehabilitation; and 6)foster the
career development of junior faculty scholars into independent investigators and academic leaders in aging
research. The impetus to study rehabilitation in disability and aging is its critical importance for the health and
quality of lifestyle older people living with chronic disability, and the dearth of mechanistic and translational
research in this area of investigation. The UM-OAIC research cores will define disease-specific disability
phenotypes, use the characteristics to design disease-specific rehabilitation strategies, and examine their effects
on the pathophysioliogic mechanisms and functional limitations associated with the disability phenotype.
Functional and clinical outcomes will be reviewed, and the efficacious rehabilitation interventions modified for
translation into community-based trials.
The program provides cohesiveness for the mechanistic research, mentored training, and dissemination of
information across collaborations with Johns Hopkins, The National Institute of Neurologic Diseases and Stroke
(NINDS), University of Maryland Medical System, Kernan Rehabilitation Center, Boston University, Wake
Forest University and University of Texas Galveston. Although the mechanisms and degree by which these
chronic diseases decrease mobility, functionality and quality of life (QOL) may differ, the clinical implications
are similar: decreased independence, depression, reduced QOL and fatigue, increased morbidity, high
healthcare utilization and costs, and high mortality rate.
II. RESEARCH, RESOURCES AND ACTIVITIES
A. CORES
1. Clinical and Translational Research Methods Core (RC 1)
Co-Leaders: Richard Macko, M.D., (410-605-7063, [email protected]) and Jay Magaziner,
Ph.D., M.S.Hyg. (410-706-3553, [email protected] )
The mission of the Clinical and Translational Research Methods Core is to design, implement, and evaluate
clinical and translational research in exercise rehabilitation and recovery in older patients with stroke, hip
fracture, and other medical conditions associated with functional limitations in aging. It is our hypothesis that
cardiovascular (CV) and neuromuscular deconditioning are both fundamental precursors, as well as sequelae of
disability and dependence in chronic diseases prevalent in the elderly. It follows that exercise and motor
learning-based rehabilitation strategies designed to enhance recovery by improving aerobic capacity and
neuromotor function can modify chronic disability. Even though aerobic and resistive conditioning, and other
motor learning-based training paradigms have remarkable potential to improve functionality, reduce risk of
recurrent morbid events and improve quality of life, there exists limited information regarding disability and
disease-specific exercise rehabilitation strategies (i.e., timing, frequency, intensity, duration, and modality)
required to produce the most desirable health outcomes under the safest conditions in these frail populations.
RC-1 provides the access and leadership to OAIC and other university researchers for the conduct of
translational rehabilitation research in functionally limited older people. The core has been organized into two
levels of translation: bench to clinical laboratory; and clinical laboratory to community.
Increasing collaborations represented by dual core leadership provide a translational research model that
focuses on the following aims:
1. To facilitate design and conduct research investigating mechanisms underlying functional limitations
associated with stroke, hip fracture and other chronic diseases in older people to determine the disability
phenotype across a spectrum of neuromuscular, cardiovascular, functional and behavioral domains.
2. To facilitate evaluation of the multi-faceted processes by which older persons who develop prevalent
age-associated disabling medical diseases such as stroke or hip fracture decline functionally, and either
recover with rehabilitation or develop comorbid medical conditions that worsen their prognosis.
3. To facilitate development and implementation of disease and disability specific exercise and motor
learning interventions, including application of new technologies, adherence strategies and treatment
fidelity to optimize clinical and functional outcomes in older individuals with functional limitations.
4. To utilize infrastructure of the Pepper Center to facilitate testing of exercise interventions at the
community level, and help investigators study the factors that could impede or facilitate the broader
dissemination of health and function promoting exercise interventions for aging populations with
functional limitations.
Core leaders will provide consultation to investigators in design, outcomes selection and analyses, quality
assurance and management to expand our smaller efficacy studies into larger community-based interventions.
RC-1 services will establish the optimal training characteristics, adherence strategies and social approaches that
are needed to optimize the conduct of community-based exercise interventions. This will establish a framework
to begin to study health policy research of exercise in aging with disability.
2. Neuromotor Function Core (RC2)
Co-Leaders: Jill Whitall, Ph.D. (410-706-0764, [email protected]), Daniel Hanley, M.D.,
(410-614-5185, [email protected]) and Mark Rogers, Ph.D. (410-706-0841,
mailto:[email protected])
The mission of the Neuromotor Function Core is to provide the expertise and investigator resources to assess
the biomechanical and neurological mechanisms of functional performance with particular emphasis on gait,
reaching and balance in older people with physical disabilities due to stroke, hip fracture or other chronic
diseases associated with aging and disability.
The aims of Research Core 2 are:
1. Provide reliable human performance measures to enhance the rehabilitation science in OAIC-supported
mechanistic and intervention studies and define the disability phenotype of older individuals with stroke,
hip fracture and other chronic disabling diseases.
2. Develop new methodology to investigate deficits in neuromotor control and brain function in older
disabled individuals and, in collaboration with RC-1, facilitate the implementation of motor learning
principles and new technologies into novel exercise rehabilitation interventions that can be tested in the
laboratory and then, if efficacious, be translated into the community.
3. Conduct research examining central and peripheral neural mechanisms in focused rehabilitation studies
that are already shown to be efficacious to better understand the mechanisms of exercise-mediated
neural adaptations underlying motor recovery and inform the design of new interventions.
4. Provide consultation, mechanistic insight and training to Junior Faculty and OIAC investigators, other
Pepper Centers and investigators studying rehabilitation of older people with physical limitations at
other institutions in the selection and use of functional and neuromotor assessment tools and assist in the
interpretation of the research findings.
It is our goal to 1) determine the central (neuroplastic) and peripheral (neuromuscular) mechanisms underlying
functional limitations in stroke, hip fracture and other chronic disabling diseases, 2) use this information to
develop new exercise and motor learning-based rehabilitation strategies, 3) re-evaluate, in the laboratory, the
efficacy of these strategies in relation to neural and motor function changes and 4) use this information to
design and implement novel exercise and motor learning based interventions that can be translated to the
community to improve the functional independence of older Americans living with chronic disability.
Accomplishing these goals will assist us in testing and proving the OAIC hypothesis that “cardiovascular and
neuromotor dysfunction are fundamental to disability in older people living with functional impairments and
that these impairments are modifiable by disease specific motor learning-based and exercise rehabilitation.”
3. Applied Clinical Physiology Core (RC3)
Co-Leaders: Leslie I. Katzel, M.D., Ph.D. (410-605-7248, [email protected]), Alice Ryan,
Ph.D. (410-605-7851, [email protected]) and Richard Macko, M.D. (410-605-7063,
[email protected])
Aging, chronic diseases, and acute events such as a stroke and hip fracture result in a reduction in physiological
reserve and functional decline. The fundamental tenet of the Applied Clinical Physiology Core is that physical
deconditioning and “learned” non-use propagate functional declines in older people. This provides a biological
rationale to implement exercise training to improve multiple physiological systems in older persons hindered by
disability. The mission of Research Core 3 is to provide a core for the standardized cardiovascular, functional,
and metabolic evaluations of UM-OAIC research subjects and assist investigators in determining the
mechanisms by which exercise rehabilitation strategies enhance function and recovery in older adults with
disabling diseases such as stroke or hip fracture.
This Core has the following specific aims:
1. To assist OAIC investigators in their examination of the effects of aging and disability on cardiovascular
deconditioning, declining functional performance and clinical physiology that leads to sarcopenia and
metabolic dysfunction, key characteristics of the functional limitations and disability phenotypes
observed in older, populations disabled by stroke (brain injury), hip fracture, and other chronic diseases.
2. To collaborate with RC-1 and RC-2 to develop, apply and study the cardiovascular, functional, and
metabolic outcomes of novel motor learning and exercise-based interventions designed to improve
clinical outcomes and lifestyle in aging and selected disability conditions.
3. To provide consultation to OAIC investigators in the application of clinical physiology, body
composition, and metabolic measurements to OAIC research in order to facilitate mechanistically driven
exercise rehabilitation research in aging and disability across the UM-OAIC in internal CDP and P/E
projects and external NIH and VA funded research.
The RC-3 plays a critical role in integrating and linking the RCs, core development projects (CDPs), junior
faculty awardees (JFA) projects, pilot and exploratory (P/E) projects in the study of exercise design, and its
conduct, and the measurement of cardiovascular fitness, metabolism and body composition.
4. Muscle Biology and Molecular Mechanisms of Inflammation Core (RC 4)
Co-Leaders: Charlene Hafer-Macko, M.D. (410-605-7000 x5413, [email protected]) and
Alice Ryan, Ph.D. (410-605-7851, [email protected] )
Increasing clinical and experimental data provide evidence that aging and physical frailty are strongly linked to
fundamental mechanisms of inflammation and oxidative injury. The fundamental hypothesis of the Muscle
Biology and Molecular Mechanisms of Inflammation Core is that common biologic mechanisms in aging are
accelerated in select disability conditions, such as stroke and hip fracture. These skeletal muscle changes may
contribute to the functional disability and risk of cardiovascular disease in individuals aging with a disability.
The mission of Research Core 4 is to investigate biologic mechanisms that underlie the disability of advancing
age at the tissue, cellular, molecular and genetic level with a focus on muscle, adipocytes, and endothelial cells.
Research Core 4 will provide consultative expertise, technical support and training, and access to services and
resources for the conduct of muscle biology research in disabled older people.
Research Core 4 focuses on the following revised aims:
1 To assist OAIC investigators who a) investigate the mechanisms responsible for sarcopenia and altered
muscle structure/function in selected disability conditions, and to determine the pathological,
histochemical, and muscle fiber metabolism similarities and differences in these disability populations;
and b) measure markers of muscle metabolism, inflammation / oxidative injury, and mitochondrial
function, to determine the biologic mechanisms underlying the metabolic abnormalities at the tissue,
cellular, and molecular level; and
2 To collaborate with RC2 and RC3 to determine whether these structural, inflammatory and metabolic
abnormalities are related to reduced muscle performance, cardiovascular fitness, body composition, and
measures of physical frailty (disability phenotype), and are modifiable by exercise rehabilitation.
3 To provide consultation and mentoring of laboratory training and oversight to Junior Faculty and OAIC
investigators as they design new studies, acquire new laboratory methodological skills, and acquire
preliminary and pilot data to compete for additional NIH funding.
The RC-4 plays a critical role in integrating and linking the RCs, CDPs, junior faculty awardees, pilot and
exploratory projects that investigate the impact of structured exercise rehabilitation regimes that target muscle
and adipose tissue, in order to define the components of the exercise prescription required to induce cellular and
tissue changes.
5. Biostatistics and Informatics Core (RC 5)
Co-Leaders: John D. Sorkin, M.D., Ph.D. (410-605-7119, [email protected]) and Michael
Terrin, M.D., MPH (410-706-6139, [email protected])
The Biostatistics and Informatics Core will gather data from the UM-OAIC research cores and studies, provide
and manage a centralized data system for the storage of study data, and perform analyses that combine data
across research cores and studies. Research Core 5 will be a focal point for all UM-OAIC research and will
promote synergy among studies and research cores producing a Center that is more than the sum of its parts.
Research Core 5 will also provide a centralized, user-friendly, secure, regularly backed-up, data management
system called GERI. GERI will be used to store, review, and access data generated by UM-OAIC researchers,
and research cores. The Tracking, Adjudication, Medication databases and the Adverse Event Reporting System
will assist researchers and leadership to manage UM-OAIC studies.
The aims of Research Core 5 are to provide services that complement the other research cores, as follows:
1. Assist UM-OAIC researchers in the design and conduct of their studies, and the analysis and
interpretation of their data by providing:
a. Centralized information system for the acquisition, storage, and review of data.
b. Informatics resources for study coordination, including a subject registry, protocol and data
tracking system, data management, and safety monitoring.
c. Ability to merge data across UM-OAIC studies to identify predictors of disability and successful
rehabilitation.
d. Confidentiality, physical security, and logical integrity of all data.
2. Teach UM-OAIC faculty, trainees, and staff statistical methods, epidemiologic principles and basics of
study design.
The BISC provides 10-years experience and continuity assisting OAIC investigators design and execute
complex studies; analyze and interpret their data for manuscripts and grant submissions. Our one-on-one
mentoring and formal didactic training of junior and senior investigators will help them become better able to
analyze their data. The support provided by the BSIC will help OAIC investigators achieve the goal of
increasing the functional independence of older Americans.
6. Leadership/Administrative Core (LAC)
Co-Leaders: Andrew P. Goldberg, M.D. (410-605-7183, [email protected]) and Jay
Magaziner, Ph.D., M.S. Hyg. (410-706-3553, [email protected])
The LAC is responsible for the overall direction, operation, administrative management and integration of the
components of the UM-OAIC to assure the accomplishment of the mission and goals of the Center. The
research and training endeavors of the OAIC are interdisciplinary; hence, the LAC merges the talents of an
interprofessional team of investigators with diverse skills and expertise in aging research. This insures the
optimal conduct of interventional research and research training related to the rehabilitation of older persons
disabled by a stroke, hip fracture, peripheral arterial occlusive disease, or other chronic diseases which limit
their functional independence.
7. Pilot And Exploratory Studies Core (P/ESC)
Co-Leaders: Mary Rodgers, Ph.D. (410-706-5658, [email protected]) and Jay Magaziner,
Ph.D., M.S.Hyg. (410-706-3553, [email protected])
The Pilot and Exploratory Studies Core provides start-up support for quality research proposals of high
relevance to the Center’s mission and aims. The UM-OAIC selects and funds pilot and exploratory research
studies to gain the knowledge necessary to develop future projects to optimize the recovery of older adults with
chronic conditions associated with aging such as stroke, hip fracture or other chronic conditions. Each
submitted proposal receives an evaluation for scientific merit by at least two external reviewers, and then by
UM-OAIC leadership (Core Leadership Executive Committee and the Program Advisory Committee) for
relevance to the Center’s mission and aims.
Pilot and exploratory studies are designed to stimulate new interdisciplinary collaborations and attract new and
established investigators from relevant disciplines to study exercise-based rehabilitation and recovery following
stroke, hip fracture, and other disabling chronic conditions. Studies will explore specific hypotheses in order to
gain insight into the underlying mechanisms of physical function decline and disability. These studies may also
involve preliminary animal/human testing of interventions that are designed to evaluate safety, feasibility,
efficacy, and/or determination of optimal time course or dosage. Exploratory studies will analyze data from
numerous ongoing and completed studies at the UM-OAIC in order to explore hypotheses that will guide the
selection and design of future studies. Both types of studies (P/ES) will complement each other and contribute
essential information that will advance our understanding of the underlying mechanisms of and possible
interventions for enhancing function and reducing disability in older persons through the use of exercise
interventions
8. Research Career Development Core (RCDC)
Co-Leaders: Andrew P. Goldberg, M.D. (410-605-7183, [email protected]) and Jay
Magaziner, Ph.D., M.S.Hyg. (410-706-3553, [email protected])
The RCDC provides an enriched, mentor-based research training and educational environment that will promote
the career development of junior scholars toward independence as investigators in aging-related rehabilitation
research and as leaders in gerontology and geriatric medicine within their respective disciplines at academic
medical centers and institutes of higher learning. The training in the RCDC provides the skills needed for the
conduct of clinical investigation that examines basic mechanisms and designs and implements targeted, diseaseand disability specific clinical rehabilitation strategies, such as treadmill exercise, upper extremity task-oriented
neuromotor training, and robotics. Trainees learn to investigate the mechanisms underlying the recovery of
neuromuscular and physiological functioning in older people who have experienced sudden and chronic
disability due to a stroke, hip fracture, or other medical conditions that are prevalent in older people. The
primary goals of the RCDC are to enrich and advance multidisciplinary research in exercise rehabilitation in
gerontology and geriatric medicine, and provide comprehensive research training for junior scholars and other
junior faculty in aging research at UMB that teaches the translation of basic mechanisms into clinical research,
and brings clinical and functional outcomes from Center-based core laboratories to “real world” community.
The specific aims of the RCDC are to:
1. Promote the growth and success of the RCDC mentor-based research-training program in aging and
rehabilitation science to meet the basic science and clinical training needs of junior scholars to prepare
them for academic careers as independent investigators.
2. Identify and educate junior faculty at UM in the skills needed to design and implement exercise
rehabilitation research in older people with disabling diseases.
3. Enhance recruitment efforts at UM and nationally to identify the brightest and most promising junior
faculty and research associates, provide research training in the mechanisms underlying the clinical and
functional effects of exercise-based rehabilitation programs in older patients with physical and
functional disabilities, and implement and evaluate these programs in the clinical laboratory and
community settings.
4. Coordinate and complement RCDC training in the Research Cores with other UM resources in aging
research, and develop collaborations with other OAICs to facilitate and sponsor specialized workshops,
training opportunities and retreats for junior scholars in research areas in common with other Pepper
Centers.
UM-OAIC Career Development Awardees
Current Awardees
2009-Present: Kathleen Michael, PhD, RN, CRRN, Assistant Professor, School of Nursing, University of
Maryland Baltimore
Dr. Michael’s goal is to develop research that integrates behavioral/motivational interventions with novel
rehabilitation exercise strategies to promote function, independence, and quality of life in individuals with
stroke. Emerging evidence shows the effectiveness of task-oriented exercise models in improving physical and
functional recovery in chronic stroke. Treadmill (TM) exercise induces significant gains in cardiovascular
fitness, improves glucose metabolism and increases walking velocity, which is linked with brain neuroplasticity.
Adaptive physical activity (APA) models improve balance, gait, and walking distances. Yet even though both
TM and APA can build the capacity to increase activity by improving endurance, balance, and gait patterns,
changing activity behaviors in everyday life remains an unmet challenge. Dr. Michael’s work focuses on
determining the behavioral interventions that need to accompany the exercise programs to help individuals with
stroke integrate health-promoting and risk-reducing activity behaviors into their daily lives. Motivational,
social, and individually-determined goal-directed activities can potentiate the effectiveness of structured
exercise programs and facilitate carry-over to improve daily mobility function after stroke.
Dr. Michael is testing the hypothesis that a combination of structured task-oriented exercise plus a home-based
behavioral intervention leads to sustained improvements in cardiovascular fitness, mobility, self-efficacy, and
sustained daily activity profiles after stroke, more than task-oriented exercise alone.
Specific Aim 1: Determine the effects of combined TM+APA + Behavioral/motivational intervention vs.
TM+APA alone on fitness, gait, balance, self-efficacy, free living activity, and self-reported outcomes related to
stroke-specific quality of life.
Specific Aim 2: Determine the durability of TM+APA and TM+APA+ behavioral intervention-associated
improvements for six months after the end of formal training.
Specific Aim 3: Determine the feasibility of translating the APA model of stroke rehabilitation exercise into
home environments, and evaluate the effects of the home program on fitness, gait, balance, self-efficacy, free
living activity, and self-reported outcomes related to stroke-specific quality of life.
UM-OAIC Junior Scholars (Research supported by the UM-OAIC, NIH K or VA CDA):
1994-1995
1994-1996
Peter Vaitkevicius, M.D., Assistant Professor Gerontology and Cardiology (Present position:
Associate Professor, University of Michigan)
Ernest Moy, M.D., MPH, Assistant Professor, Internal Medicine, University of Maryland
1994-1997
1994-1997
1996-1998
1996-1999
2001-2004
2001-2004
2001-2004
2001-2004
2001-2004
2004-2006
2004-2006
2004-2006
2004-2007
2004-2007
2005-2008
2005-2008
2007-present
2007-present
2008-present
2008-present
2009-present
2009-present
Baltimore (Present Position AAMC)
Andrew Gardner, Ph.D., Assistant Professor, Gerontology, University of Maryland Baltimore
(Present position: Professor, Department of Kinesiology, University of Oklahoma)
Lois Killewich, M.D., Ph.D., Assistant Professor, Surgery (Vascular Medicine) (Present
position: Associate Professor, University of Texas, Galveston)
Barbara Bartman, M.D., MPH, Assistant Professor, Internal Medicine, University of
Maryland Baltimore (Present position: Research Instructor, Johns Hopkins Hospital)
Richard Macko, M.D., Assistant Professor, Department of Neurology, University of Maryland
Baltimore (Present position: Associate Professor, University of Maryland Baltimore)
Larry Forrester, Ph.D., Assistant Professor, Department of Physical Therapy, University of
Maryland Baltimore (Subsequent Funding: VA Advanced Career Development Award:
Development of Ankle Robot Model with Treadmill Training in Chronic Stroke.)
Marianne Shaughnessy, Ph.D., CRNP, Assistant Professor, School of Nursing, University of
Maryland Baltimore (Subsequent Funding: Maryland Statewide Health Network Grant through
the Maryland Cigarette Restitution Fund Program Exercise and Diet Programs to Improve
Cardiovascular Health in a West Baltimore Faith Community)
Denise Orwig, Ph.D., Assistant Professor, Department of Epidemiology and Preventive
Medicine, University of Maryland Baltimore (Subsequent Funding: NHLBI via UMDNJ:
functional Outcomes in CV Patients Undergoing Surgical Hip Repair (FOCUS)
Frederick Ivey, Ph.D., Assistant Professor, Department of Medicine, University of Maryland
Baltimore (Subsequent Funding: NIH/NIA KO1 AG 091242. Effects of Exercise on Endothelial
Function in Chronic Hemiparetic Stroke Patients)
Carwile LeRoy, M.D., Assistant Professor, Department of Medicine, University of Maryland
Baltimore
Jacob Blumenthal, M.D., Assistant Professor, Department of Medicine, University of
Maryland Baltimore
Eun-Shim Nahm, Ph.D., RN, Assistant Professor, Department of Organizational Systems and
Adult Health, School of Nursing, University of Maryland Baltimore
Federico Villagra, Ph.D., PT, Assistant Professor, Department of Physical Therapy and
Rehabilitation Sciences, University of Maryland Baltimore
Kris Ann Oursler, M.D., Assistant Professor, Division of Gerontology, University of
Maryland Baltimore
Ram Miller, MDCM, MSc, Assistant Professor, Division of Gerontology, Department of
Epidemiology and Preventive Medicine, University of Maryland Baltimore
Sandy McCombe Waller, Ph.D., Assistant Professor, Department of Physical Therapy and
Rehabilitation Sciences, University of Maryland Baltimore
Stephen Seliger, M.D. Assistant Professor, Department of Medicine, University of Maryland
Baltimore
Steven Prior, Ph.D. Assistant Professor, Division of Gerontology, University of Maryland
Baltimore (VA CDA)
Wilbur Chen, M.D. Assistant Professor, Department of Medicine, University of Maryland
Baltimore (NIH K)
Afshin Parsa, M.D., MPH Assistant Professor, Department of Medicine, University of
Maryland Baltimore (NIH K)
Alan McMillan, Ph.D., Research Associate, Diagnostic Radiology and Nuclear Medicine,
University of Maryland Baltimore (UM-OAIC pilot)
Kathleen Michael, Ph.D., RN, CRRN, Assistant Professor, Department of Organizational
Systems and Adult Health, School of Nursing, University of Maryland Baltimore
Deepak Deshpande, DVM, Ph.D., Assistant Professor, Department of Medicine, Division of
Pulmonary and Critical Care Medicine, University of Maryland Baltimore
2010-present
B.
Giora Netzer, M.D., MSCE, Assistant Professor, Department of Epidemiology and Public
Health, University of Maryland
RESEARCH
Below is a listing of the current Center supported studies and brief description about several of the major
supported studies.
Major Grants Associated with the UM-OAIC
Investigator
Center Grants
A. Goldberg
R. Macko
A. Shuldiner/
A. Goldberg (CoDirector)
A. Shuldiner/
A. Goldberg (Clinical
Core Director)
Training Grants
A. Goldberg
A. Goldberg
J. Hagberg
J. Magaziner
J. Warnick
M. Rogers
External Projects
D. Alley
Grant Title
Geriatric Research Education and Clinical Center (GRECC) (RC 1, 2, 3, 4, 5, RCDC)
VA Center of Excellence Task-Oriented Exercise and Robotics in Neurological Disease
(MERCE) (RC 1, 2, 3, 4, 5, PESC, RCDC)
NIH P30 DK 072488 - Nutrition Obesity Research Center (NORC) (RC 1, 2, 3, 4, 5)
NIH P60 DK079637 - Baltimore Diabetes Research and Training Center (DRTC) (RC 1, 2, 3,
4, 5)
T32 AG00219 - The Biology of Exercise, Metabolism and Aging (RCDC)
VA Special Fellowship (RCDC)
T32 AG0002678 - Predoctoral Training in Exercise Physiology and Aging (RCDC)
T32 AG000262 - Training in Epidemiology of Aging (RCDC)
T35 AG036679 - Short-term Training Program on Aging (RCDC)
H133P100014 - University of Maryland Advanced Neuromotor Rehabilitation Research
Training (UMANRRT) (RCDC)
A. Bastain
A. Bastain
J. Blumenthal
A. Cernich
F NIH - Diagnosis of clinically Important Weakness in Older Adults: The InCHIANTI study
(RC 1, 5, RCDC)
VA Merit - Effects of exercise and cognitive training on executive function in PD (RC 1, 2, 3,
5)
VA Career Development Award (CDA) - Reaching While Maintaining Balance in Dimensional
Space (RC 1, 3, 5)
NIH/NICHD 1R01 HD40289 - Mechanisms and Rehabilitation of Cerebellar Ataxia (RC 3)
NIH/NICHD 1R01 HD0478741 - Human Locomotor Plasticity in Health and Disease (RC 3)
VA T32 Pilot Project - Decreasing Barriers to Care for Veterans with Dementia (RC 3, 5)
VA CDA - Effects of Exercise Training on Neurocognitive Function after Stroke (RC 1, 2, 3)
M. Dux
VA CDA - Exercise and autonomic, cognitive, and affective function post-stroke (RC 1, 2, 3)
L. Forrester
VA Merit (pilot) - Ankle Robotic Training after Stroke: Effects on Gait and Balance (RC 1, 2,
3)
MERCE Project - Modular Lower Extremity Robotics Assisted Exercise After Stroke (RC 1,
2, 3, PESC)
R25 HL092604 - University of Maryland Summer Training and Research (STAR) Program
(RC 3)
5U01 NS062851 - Clot Lysis: Evaluating Accelerated Resolution of IVH Phase III (CLEAR
III) (RC 2)
5R01 NS046309 - ICH Removal: Minimally Invasive Surgery + rt-PA (MISTIE) (RC 2)
VA Merit - Strength Training for Skeletal Muscle Adaptation after Stroke (RC 1, 2, 3, 5)
VA MERCE Project – Treadmill Exercise Prescriptions to Improve Fitness vs. Ambulatory
Function After Stroke (RC 1, 2, 3, 4, 5)
K. Anderson
J. Barton
L. Forrester
J. Hagberg
D. Hanley
D. Hanley
F. Ivey
R. Macko
Investigator
J. Magaziner
J. Magaziner/R.
Craik
S. McCombe-Waller
S. McCombe-Waller
S. McCombe-Waller
E.S. Nahm
D. Orwig/L.
Fredman
K. Oursler, site PI
K. Oursler
S. Prior
S. Prior (co-PI)
M. Rogers
M. Rogers
A. Ryan/ C. HaferMacko
A. Ryan
S. Seliger
L. Katzel co-PI
M. Shaughnessy
M. Shaughnessy/F.
Ivey
A.Shuldiner
M. Stuart/R. Macko
M. Terrin
M. Terrin
S. Waldstein PI,
L. Katzel site PI
S. Waldstein
J. Whitall
J. Whitall
G. Wittenberg
G. Wittenberg
G. Wittenberg/
C. Bever (PI)
Pilots
W. Chen
R. Cross
D. Deshpande
Grant Title
R01 AG029315 - Epidemiology of Bone Strength and Muscle Composition after Hip Fracture
in Men (RC 1, 3)
R01 AG035009 - Community Ambulation Following Hip Fracture (RC 1, 3)
UM-OAIC CDP – Combining Bilateral and Distal Arm Training to Promote Arm and Hand
Recovery in Patients with Chronic Hemiparesis (RC 2, 3, 5)
R21 HD042125 - Combing Proximal and Distal Arm Training for Patients with Chronic
Hemiparesis (RC 1, 2, 3, 5)
Supplement to R21 (RC 2)
R01 NR011296 - Dissemination of a Theory-Based Bone Health Program in Online
Communities (RC 1, RCDC)
R01 AG028556 (sub-contract) - Biological Pathways of Acute and Chronic Stress in Aged
Hip Fracture Caregivers (RC 1, 3)
1R01 HL095136 - Cardiovascular Disease Mechanisms in HIV Infected and Uninfected
Veterans (PI: Freidberg) (RC 1, 3)
R01 HL095136-01- Cardiovascular Disease Mechanisms in HIV Infected and Uninfected
Veterans (RC 3)
VA CDA - Aging, Angiogenesis and Metabolic Responses to Aerobic Exercise (RC 1, 3)
R21 - Translational Studies of a Novel cardiovascular Disease Risk Factor Endothelial (RC
3)
1R01 AG029510 - Lateral Stability and Falls in Aging (RC 1, 2, 3, 5)
1R01 AG033607 - NIH/National Institute on Aging Intervention to Enhance Lateral Balance
Function and Prevent Falls in Aging (RC 1, 2, 3, 5)
1R01 AG030075 - Aging, Inflammation and Exercise in Chronic Stroke (RC 1, 2, 3, 4, 5)
VA Merit - Exercise, Inflammation and Pro-thrombotic Modulators in the Elderly (RC 1, 3, 4, 5)
VA Merit - Neurocognition and Functional Performance in Older Veterans with CKD (RC 1, 3,
5)
VA Center of Excellence in Robotics and Exercise- Reshaping Exercise Habits and Beliefs
(REHAB) Following Stroke (RC 1, 3, 5)
VA Merit - Veterans with Stroke Translating Exercise Programs (RC 1, 3, 5)
U01 HL105198 - Pharmacogenomics of Anti-Platelet Intervention-2 Study (RC 3)
VA Merit - Adaptive Physical Activity for Chronic Stroke (RC 1, 3)
R01 Pending - NHLBI - Non-Invasive Treatment of Abdominal Aortic Aneurysm Clinical Trial
(RC 1, 5)
U01 HL074815 - NIA - Focus Data Coordinating Center (RC 1)
1R01 AG034161 - Race, Socioeconomic Status, and the Brain: HANDLS Scan Substudy
(RC 3)
5 R01 AG015112 - Hypertension, Cognition and the Brain in Older Adults (RC 1, 3)
R21 HD047756 – Bilateral and Unilateral Training in Stroke
R03 AG030349 - Treadmill Training with Rhythmic Auditory Cueing in Older Adults with
Chronic Stroke (RC 1, 2, 3, 5)
Pending: Impact/Priority Score: 16
Percentile: 2.0 - Driving Cortical Plasticity for Rehabilitation of Reaching After Stroke (RC 2)
VA Merit - Biological Prediction & Correlation of Response to Robotic Arm Therapy (RC 2)
VA Merit - Evaluation of Robot Assisted Neuro-Rehabilitation (RC 2)
K12 and UM-OAIC Pilot - Immunologic Dysfunction in Elderly Subjects who undergo Aerobic
Exercise Rehabilitation (RC 3, PESC)
UM-OAIC Pilot - Impact of Inflammatory Bowel Disease and Aging on Body Composition and
Functional Performance (RC 1, 3, 5, PESC)
UM-OAIC Pilot - The Effects of Aging on Airway Smooth Muscle Contraction and Relaxation
(RC 3, PESC)
Investigator
L. Forrester
K. Michael
Grant Title
UM-OAIC Pilot – Interactive Visumotor Ankle Robot Training after Stroke ((RC 1, 2, 3, 5,
PESC)
UM-OAIC Pilot - Testing Adaptive Physical Activity in Stroke (RC 1, 2, 3, 5, PESC)
K. Michael
UM-OAIC Pilot - Virtual Cohorts for Home-based Stroke Rehabilitation: Using Technology to
Integrate Exercise Behaviors into Everyday Life (RC 1, 3, 5, PESC)
R. Miller
UM-OAIC Pilot – The Effect of Home-Based Exercise Training on Recovery of Lower
Extremity Function and Inflammatory Cytokines in Hip Fracture Patients (RC 1, 3, PESC)
A. Parsa
UM-OAIC Pilot - Endothelial Function and Cognitive Dysfunction in Chronic Kidney Disease
(RC 1, 3, PESC)
S. Prior
UM-OAIC Pilot - Effects of aerobic exercise training on VEGF, angiogenesis and glucose
metabolism in older adults (RC 1, 3, 5, PESC)
M. Rogers
UM-OAIC Pilot – Hip Muscle Composition: Relationships with Neuromechanical
Performance, Lateral Stability, and Risk of Falls in Older Adults (RC 1, 2, 3, 5, PESC)
Pilots (Pepper III) Year 5 – Pending
A. Faden
UM-OAIC Pilot - Role and Mechanism of Exercise Induced Facilitation of Recovery after
Experimental Traumatic Brain Injury (RC 2)
R. Miller
UM-OAIC - Pilot study of prehabilitation prior to elective surgery in older adults (RC 1, 2, 3,
4, 5, PESC)
G. Netzer
UM-OAIC Pilot - Effect of a progressive, adaptive physical activity regimen on functional
outcomes and musculoskeletal composition in elderly survivors of critical illness (RC 1, 3, 5,
PESC)
K. Oursler/
UM-OAIC Pilot - Functional and metabolic benefits of rehabilitation in HIV (RC 1, 3, 5, PESC)
H.Ortmeyer
B. Beamer
UM-OAIC Pilot and MERCE - Pilot Does strength training improve balance training in older
adults? (RC 1, 2, 3, 5, PESC)
1. Epidemiology of Bone Strength and Muscle Composition After Hip Fracture in Men (R01 AG029315,
PI: J. Magaziner, Ph.D., MSHyg)
Hip fracture, a disabling and costly condition to individuals and society, is typically thought of as a health
problem of older women. Approximately 25 to 30% of the 350,000 hip fractures in the US occur in men, 1, 2 yet
the number of men included in studies of hip fracture consequences has been small. It is estimated that by
2025, the incidence of hip fracture in men will be the same as that currently seen in women, making this an
emerging public health concern for older men, their families, and the healthcare system.1, 3
Our working hypothesis is that men and women will have different trajectories of loss and recovery after hip
fracture. More specifically, it is hypothesized that men who fracture a hip will experience greater declines in
bone mineral density and bone strength, muscle mass and strength, and will gain more fat than women who
sustain a hip fracture, and men will experience less recovery and will recover more slowly than women in
multiple functional domains. Men also will reduce their level of physical activity and be less active postfracture than women and will be less motivated to engage in rehabilitative strategies to improve their chances of
recovering. In addition, it is anticipated that bone turnover, hormone effects, and cytokine regulation following
fracture will differ by sex. In evaluating these differences, we will test the hypothesis that at least moderatelysized sex difference in outcomes exists in many if not all areas of functional, physiological and metabolic
change. Finally, it is hypothesized that men who fracture a hip will differ in functional, physiologic and
metabolic outcomes from similar men who do not fracture, and that the amount of change will be greater among
hip fracture patients.
The primary aims of the proposed study are to:
1. Describe the trajectories of components of bone strength, including bone mineral density, ultrasound
properties, and bone geometry in men with hip fractures during the year after fracture and contrast this
with these components in women with hip fractures.
2. Describe the trajectories of non-bone components of body composition, including muscle and fat mass,
in men during the year after hip fracture and to contrast these with observations in women.
3. Describe the trajectories of physical activity, neuromuscular function (including strength), and physical
functioning in men and to compare these to trajectories observed in women during the year after hip
fracture.
4. Describe the trajectories of (a) psychosocial function (depression; social interaction; quality of life), (b)
cognition, and (c) motivation (self-efficacy and outcome expectations) related to participation in
rehabilitation/exercise and adherence to medication for the treatment of osteoporosis in men during the
year after hip fracture, and to contrast these with women post hip fracture.
5. Describe metabolic factors, including biochemical markers of bone turnover (serum N-terminal crosslinking telopeptide of type I collagen and bone-specific alkaline phosphatase), hormones (testosterone,
estrogen, sex hormone binding globulin, parathyroid hormone, insulin-like growth factor 1, and vitamin
D) and the pro-inflammatory cytokine interleukin-6 during the year after hip fracture and to compare
trajectories observed in men and women.
6. Determine the differences in selected aspects of bone, muscle, function, activity, and metabolism that are
attributable to hip fracture vs. those that occur in similarly frail older men who do not sustain a hip
fracture.
The secondary aims of this project are to:
1. Collect and store serum, plasma, buffy coat specimens, and obtain consent to perform genetic tests so
that we can, in the future, evaluate additional hormone and cytokine regulators, as well as candidate
genes for polymorphism and levels of gene expression, in relation to changes in body composition and
function after hip fracture.
2. Obtain death certificates in order to further examine the pattern of survival and the specific causes of
death in men vs. women.
3. Investigate, in an hypothesis generating manner, the effects of frailty, comorbidity and functional
impairment at the time of fracture on changes (metabolic, physiologic, and functional) that follow hip
fracture, and examine whether these associations differ by sex. In addition to generating hypotheses,
these data will be used to determine sample size requirements for further focused investigations of
prognostic factors for and mechanisms underlying these changes, and to design targeted interventions to
enhance recovery post-fracture.
Supported by RC 1 and 5
2. Reshaping Exercise Habits and Beliefs (REHAB) following Stroke (VA Center of Excellence in
Robotics and Exercise, PI: M. Shaughnessy, Ph.D., CRNP)
Stroke is the leading cause of disability in the United States, and a major health concern in the older population.
Following conventional rehabilitation, many stroke survivors adopt sedentary activity patterns that contribute to
a cycle of “learned non-use” and cardiovascular deconditioning that compounds disability.
Previous research of exercise in older adults suggests they face multiple physical and psychological barriers to
exercise, including fatigue, physical deconditioning, lack of knowledge regarding benefits, low confidence in
their ability to exercise, fear of hurting themselves or falling, and lack of specific direction regarding safe and
effective exercise routines for application in home and community. Exercise studies with older adults suggest
self-efficacy and outcomes expectations are central to the adoption and maintenance of exercise behavior in
older adults. Little work has been done exploring the relationship between self-efficacy and outcome
expectations with exercise among adults post stroke.Our REHAB program (Reshaping Exercise Habits and
Beliefs) is designed to improve exercise adherence by altering self-efficacy and outcome expectations. The
program educates survivors about benefits of exercise, encourages subjects to exercise by providing a home
based regimen of walking, customized daily “homework” tasks tailored to LE deficit profiles, feedback and
goals based on measured daily ambulatory performance, and identifies/addresses barriers to mobility recovery
during the sub-acute stroke period. Regular performance of individually designed exercise programs assists
survivors in translating and sustaining mobility gains into daily activities and functional tasks, ultimately
improving social participation and community reintegration, a goal of WHO ICI-D2. This randomized study
investigates the hypothesis that REHAB will increase self-efficacy and outcome expectations for exercise, daily
activity, ambulatory function and QOL compared to matched attention controls.
The specific aims are to test effects of REHAB education/motivational program:
1. to strengthen self-efficacy and outcome expectations for exercise through an educational/motivational
program (REHAB) as evidenced by the Stroke Exercise Survey and knowledge test scores;
2. to improve daily exercise adherence based on verbal report and exercise calendars;
3. increase community-based ambulatory activity as measured by microprocessor-linked step activity
monitors and self selected floor walking velocity;
4. improve self reported quality of life and increased functional activity/social participation as evidenced
by improved scores on self report questionnaires.
Our results will determine the efficacy of an innovative motivational intervention to improve exercise and
mobility adherence across the sub-acute stroke recovery period. This will provide knowledge to design future
interventions exploring the synergy of motivational strategies with aerobic training and robotics
Supported by RC 1, 3, 5
3. Treadmill Exercise Prescriptions to Improve Fitness vs. Ambulatory Function after Stroke (VA
MERCE, PI: R Macko, M.D.)
Understanding optimal exercise formula(s) to produce specific physiological and functional effects is key to
optimizing outcomes after stroke. In addition, delineating temporal profiles and durability of exercise outcomes,
and impact of training strategy on these features, is requisite to defining the minimal and optimal training
durations to improve long-term health outcomes. Our new data shows TM training increases bold fMRI voxel
area during P knee movement in bilateral motor cortex. We do not know whether these measures of
neuroplasticity are differentially mediated by duration vs. velocity-based training, or optimized by 3 months
training, a time when our data shows a relative plateau in ambulatory performance gains. Further, our studies
reveal progressive gains in V02 peak across 6 months, but many patients did not gain in fitness until the 3rd to
6th month. This is a much longer training duration than conventional care, suggesting requirements for exercise
training are different than conventional post-stroke rehabilitation. This study investigates the hypothesis that in
chronic stroke patients a 6-month program of TM exercise progressed on the parameter of training velocity will
optimize gains in CV fitness, compared to a duration-based training progression that will optimize gains in
ambulatory function.
The aims are to:
1. Determine the effects of velocity versus duration based training on CV fitness in stroke patients by
measuring peak exercise capacity, cardiac output, and kinetics of oxygen consumption during treadmill
exercise testing with open circuit spirometry.
2. Determine the effects of velocity vs. duration based training on ambulatory function measured by timed
walks, gait biomechanics, and free-living ambulatory activity levels, and whether changes in ambulatory
function are related to brain neuroplasticity measured by BOLD fMRI of P knee movement.
3. Determine the temporal profile and durability of treatment according to training strategy by repeated
measures of fitness and function after 3- and 6-months training, and 6 months post- training cessation.
Supported by RC 1, 2, 3, 4, 5
4. Bilateral and Unilateral Training in Stroke (NIH R21 HDO47756, PI: J. Whitall Ph.D.)
Upper extremity impairment is a major functional and quality of life problem for the chronic, moderate to
severely impaired stroke survivor. Currently there are many approaches to rehabilitation with most selecting to
train the paretic arm unilaterally and a few promoting bilateral approaches. The present project will test whether
there are any functional advantages and underlying neurophysiological differences for bilateral compared to
unilateral training in a tightly controlled design. If our hypothesis is supported, the impact will be to pursue
BATRAC as a bilateral protocol for this population, and secondarily to raise the question of whether unilateral
approaches can benefit from including a bilateral approach. The goal of this study is to evaluate unilateral vs.
bilateral arm use in BATRAC, while simultaneously investigating underlying central and peripheral
mechanisms through functional magnetic resonance imaging (fMRI), single/paired pulse transcranial magnetic
stimulation (TMS) and electromyograms (EMG). We hypothesize that six weeks of BATRAC will be more
effective than six weeks of UNITRAC training in improving motor function in patients with chronic moderate
to severe UE hemiparesis through mechanisms mediated by observed changes in neurophysiological structure,
functioning and intracortical facilitation and inhibition.
Specifically, we will compare six weeks of bilateral (BATRAC) training vs. six weeks of unilateral
(UNITRAC) training and determine which is more effective in improving function in stroke patients of
moderate to severe arm impairment. Second, we will use fMRI, single pulse TMS and EMG to determine
changes in left/right hemisphere activation and muscle contraction patterns, respectively, during upper
extremity (UE) movement after unilateral and bilateral training. This will demonstrate neurophysiological
mechanisms that may differ between the two types of training. Third, using dual-pulse TMS we will determine
intracortical facilitation and inhibition after unilateral and bilateral training that will give insight into the role of
cortical disinhibition as a mechanism of neurorehabilitation.
Supported by RC 1, 2, 3, 5
5. Exercise, Inflammation and Pro-thrombotic Modulators in the Elderly (VA Merit, PI: Alice S. Ryan,
Ph.D.)
The prevalence of obesity continues to escalate in men and women over the age of 60. A sedentary lifestyle and
the significant increase in obesity with aging are associated with insulin resistance, promote the development of
cardiovascular disease and increase mortality risk. Inflammation plays a critical role in insulin resistance and
the development of type 2 diabetes. Lifestyle changes such as weight loss and physical activity are advocated
for the treatment of these chronic diseases and endpoints, and data are emerging which suggest that these
treatments may be beneficial, in part, due to their anti-inflammatory effects.
The specific objectives of this study are to determine
a) the effects of weight loss alone vs. aerobic exercise training alone on adipokine secretion and expression
(TNFalpha, adiponectin, PAI-1) in older individuals;
b) the effects of weight loss vs. aerobic exercise on adipose tissue and skeletal muscle inflammatory proximal
receptor expression (adipoR1, adipoR2, TNFR1, TNFR2 expression) and intermediate signaling pathways
(AMPK, IKKb, NFkB, JNK activity), and the terminal inhibitory action on IRS-1 tyrosine phosphorylation,
IRS-1 phosphorylation (Ser307) and Akt activity; and
c) whether the changes in ligand concentrations, receptor expression, and signal transduction are associated with
changes in peripheral (whole body insulin sensitivity by a hyperinsulinemic-euglycemic clamp), hepatic
(hepatic glucose production, HGP), and cell-type specific (insulin stimulated glucose transport in adipocytes)
insulin sensitivity.
Sixty-two overweight/obese (BMI=25-35 kg/m2) men and women aged 60-75 years will be randomly assigned
to either a 6 month weight loss (250-350 kcal/day deficit) or aerobic exercise (70-75% heart rate reserve) group
(n=31 per group). We will measure plasma circulating cytokine levels and subcutaneous abdominal AT- TNF
alpha, adiponectin, and PAI-1 secretion, tissue content, and/or mRNA expression by adipose tissue biopsy,
tissue culture, and quantitative RT-PCR. In adipose tissue (AT) and skeletal muscle (SM) obtained by vastus
lateralis biopsy, we will determine adipoR1, adipoR2, TNFR1, and TNFR2 expression by quantitative RT-PCR.
Finally, we will examine AT and SM- AMPK, IKK, JNK, and IRS1-Ser (307) phosphorylation activity in the
basal state and IRS-1 tyrosine phosphorylation, and Akt activity in the insulin-stimulated state (3-hr
hyperinsulinemic-euglycemic clamp) by immunoprecipitation and/or western blotting before and after each
intervention. A direct examination of inflammatory and pro-thrombotic modulators after weight loss alone or
exercise training alone is the first step in answering which intervention affects the local secretion of cytokines in
adipose tissue as well as cytokine receptor expression in skeletal muscle and signal transduction in both tissues.
We propose a unique combination of experiments geared toward providing greater insight into the biological
underpinnings for improved whole body and tissue specific insulin sensitivity and reduced cardiovascular
disease and stroke risk resulting from exercise and diet lifestyle modifications. Identification of effective
therapies that reduce chronic inflammation for veterans is important given the adverse health effects of a
chronically elevated inflammatory state. The prevention and treatment of insulin resistance and its
cardiovascular disease complications could effectively result in a substantial reduction in VA health care costs.
Supported by RC 1, 3, 4, 5
6. Effects of aerobic exercise training on VEGF, angiogenesis and glucose metabolism in older adults
(VA CDA, Obesity Society and Pepper Pilot, PI: Steven J. Prior, Ph.D.)
More than 20 million Americans suffer from diabetes and its associated complications. Impaired angiogenesis is
one such complication that can also limit insulin, glucose, and oxygen delivery to skeletal muscle. The
mechanism for impaired angiogenesis in T2DM likely involves reduced vascular endothelial growth factor
expression due to impaired insulin signaling, as well as increased expression of inflammatory cytokines. We
hypothesize that decreased p38 MAPK, Akt, and STAT3 signaling, as well as increased NF-κB activity and
TNFα expression lead to reduced VEGF expression and skeletal muscle capillarization in older, sedentary
individuals with IGT, and that AEX training will improve insulin signaling and VEGF expression to enhance
capillarization, thereby improving glucose metabolism. Further, to differentiate the contributions of AEXinduced improvements in capillarization (long-lasting) from those in protein expression and insulin signaling
(short-lived), we will investigate the effects of 14 days of detraining, which should reduce the contribution of
insulin signaling pathways dramatically with little change in capillarization-induced improvements in glucose
utilization (M).
The specific aims of this project are:
1) Determine the mechanisms by which skeletal muscle capillarization is reduced in older individuals with
glucose intolerance by measuring basal and insulin-stimulated VEGF expression and activation of its regulatory
proteins (p38 MAPK, Akt, and STAT3), NF-κB activity, and TNFα expression in vastus lateralis skeletal
muscle, and M during a hyperinsulinemic-euglycemic clamp in subjects with IGT and compare to those with
NGT.
2) Determine the mechanism by which AEX improves insulin signaling, VEGF expression, skeletal muscle
capillarization, and glucose metabolism in older individuals with glucose intolerance by measuring insulin
signaling, VEGF expression, skeletal muscle capillarization, and M (as in Aim 1) after 6 months of AEX in
subjects with IGT and NGT.
3) Distinguish acute from chronic effects on AEX training on glucose metabolism by examining the effects of a
14-day detraining period (after completion of 6 months of AEX) on insulin signaling mechanisms, skeletal
muscle capillarization, and M (as in Aim 1).
Subjects will be grouped by glucose tolerance status (IGT and NGT) and studied before and after 6
months of AEX and 14 days of detraining. Subjects in the NGT group will be matched to those with IGT for
age (±2 yrs), BMI (±1kg/m2), and groups will be balanced for race and sex. For this pilot, we will enroll 18
subjects and we anticipate that 12 (6 per group) will complete the intervention and all testing. At each time
point, subjects will undergo 80 mU/m2/min hyperinsulinemic-euglycemic clamps to measure glucose
utilization, as well as basal and insulin-stimulated skeletal muscle biopsies. Skeletal muscle capillarization will
be measure by histochemistry. VEGF and TNFα gene and protein expression will be measured by RT-PCR and
ELISA, respectively. Insulin signaling (p38 MAPK, Akt, and STAT3 phosphorylation) will be measured by
Western blot with protein- and phospho-specific antibodies.
This patient-oriented translational research study will determine some of the mechanisms by which AEX
training improves angiogenesis and glucose metabolism. This project relates to the theme of the Claude D.
Pepper OAIC as it is an exercise intervention that investigates the pathophysiology of insulin resistance in
aging, deconditioned individuals. This will potentially reduce health care costs and improve the quality of life in
older adults by reducing the risk of T2DM and its microvascular complications and our techniques can be
applied to other disability conditions (e.g., stroke) and the results compared across the populations.
Supported by RC 1, 3, 4, 5
7. Combining bilateral and distal arm training to promote arm and hand recovery in patients with
chronic hemiparesis (Pepper CDP, PI: Sandy McCombe Waller Ph.D., PT, NCS)
The recovery of useful hand function after stroke is most probably the major scientific challenge for stroke
rehabilitation treatment today 1 2. Novel strategies targeting active rehabilitation of hand function for moderate
to severe hemiparesis are needed. There is evidence that repetitive upper extremity training can improve neural
control of specifically targeted muscle function(s) long after spontaneous recovery and initial rehabilitation
have ceased 3-5. New training protocols such as Bilateral Arm Training with Rhythmic Auditory Cueing
(BATRAC) and Constraint Induced Therapy (CIT) provide for the first time the possibility that a stroke
survivor may regain, at lease partial, use of the arm long after the expected rehabilitation window. However,
BATRAC has shown limited change in functioning of the hand because it is focused on proximal muscles and
CIT is not useful for those without preserved hand function. We propose that it is the combination of proximal
and distal arm training strategies that can potentially provide a major improvement over proximal training alone
and reach a wider range of patients than CIT. This study will test the hypothesis that a direct targeting of the
control of both shoulder and hand muscle groups, sequentially, during upper extremity rehabilitation is
important for improved neural control and required to affect notable functional improvement of both arm and
hand use for those individuals who have no functional use of the hand prior to training.
The Saeboflex device is a new dynamic hand assist that we propose to couple with a custom-designed unilateral
training program based on motor learning principles including repetition, goal directed and task oriented
training involving active paretic hand use. However, pilot work indicates that patients with little initial proximal
arm use are not able to take advantage of this program. Therefore we propose, to combine this distal training
program with a proximal one, namely Bilateral Arm Training with Rhythmic Auditory Cueing (BATRAC) that
has already shown benefits with chronic patients in motor function 4 as well as biologic plausibility via reorganization of central motor networks as detected by functional magnetic resonance imaging (fMRI) change.
In parallel, we will build on this previous work by determining neural adaptations associated with the
combination of these training programs by measuring the adaptations for both elbow and hand function to
determine if and how the sequential combination of programs alters the underlying mechanisms. Forty patients
with moderate to severe chronic hand paresis will be randomized into two training groups comparing 12 weeks
of the sequential combination of BATRAC ( 6 wks) followed by Saeboflex training (6 wks) to a control
group receiving 12 weeks of passive stretching and splinting of the hand. Motor function and fMRI imaging
will take place pre- and post training. The overall long-term objective of our research is to understand the
principles and mechanisms underlying UE control and enhanced stroke recovery in order to provide a scientific
basis for treatments of this population.
Hypothesis: Combining 6 weeks of BATRAC and 6 weeks of motor training with Saeboflex will result in
better and more durable neural and functional changes in paretic upper extremity of patients with chronic hand
paresis compared to 12 wks of passive stretching control.
Specific Aim #1: To determine the effects and durability of 12 weeks arm training with the combination of
BATRAC (6 wks) and Saeboflex (6 wks) compared to 12 weeks training of passive stretching control in
reversing chronic arm and hand functional disability.
Specific Aim #2: To determine and characterize the neural reorganization for elbow and hand function after 6
weeks BATRAC compared to 12 weeks combination BATRAC and Saeboflex and 12 weeks of control training
through fMRI imaging.
Study deliveables: Accomplishing these aims will begin to determine the mechanisms of arm and hand control
and translate this into novel rehabiliation strategies for optimizing functional use of the paretic hand in those
patients with chronic hand paresis who have typically been ignored or under treated. Individual analyses of the
sub-groups of cortical /subcortical and moderate/ severe impairment will lead to future hypotheses and further
the goal of optimizing and individualizing these training approaches. A future goal is to apply Saeboflex either
combined or alone, to the sub-acute population where early recovery of some hand function may have even
greater long-term benefits for patients.
Supported by RC 2, 3, 5
8. Strength Training for Skeletal Muscle Adaptation after Stroke (VA Merit: F. Ivey, Ph.D.)
Chronically disabled stroke survivors experience accelerated skeletal muscle atrophy and other detrimental
changes to muscle and surrounding tissues on the paretic side. This unilateral tissue-level damage contributes to
worsening disability and insulin resistance. This Merit Award will advance our understanding of the potential
for strength training (ST) to reverse stroke-related muscle abnormalities to improve metabolic health, strength,
and function. It will be the first study to thoroughly investigate the effects of ST on muscle atrophy,
intramuscular fat, muscle fiber characteristics, capillary density and insulin sensitivity after stroke. We
investigate the hypothesis that a novel, high intensity, high repetition ST program will improve abnormalities in
paretic and non-paretic leg muscle volume and composition compared to an attention-matched control regimen
of supervised stretching over a 3-month intervention period in older veterans disabled by stroke. We further
hypothesize that ST-induced skeletal muscle adaptation will translate into improved insulin sensitivity, strength,
and function in this population.
Aim 1) Determine the effects of ST compared to a control intervention on paretic and non-paretic abnormalities
in skeletal muscle volume, intramuscular fat, muscle fiber distribution, muscle capillary density, and muscle
inflammation in chronically disabled stroke survivors.
Aim 2) Determine the effects ST compared to a control intervention on insulin sensitivity in stroke survivors,
and whether structural and cellular skeletal muscle mechanisms contribute to improvements in insulin
sensitivity after ST.
Aim 3) Determine the effects ST compared to a control intervention on physical function (strength, walking
speed and balance) in stroke survivors, and whether structural skeletal muscle mechanisms predict ST-induced
functional improvement.
Significance: Developing evidence-based therapies to combat skeletal muscle deterioration is highly relevant
for chronically disabled stroke survivors. There is mounting evidence that current models of post-stroke
rehabilitation are not optimal for maximizing recovery of muscle mass, strength, and metabolic health. This
research will develop new insight into the utility of progressive ST for reversing detrimental changes to gross
muscle composition, muscle molecular phenotype, muscle inflammation, and muscle capillarization. Changes to
any or all of these muscle parameters should have measurable impact on both whole body insulin sensitivity and
function. Collectively, the results from this trial may change the current standard of care for stroke survivors by
providing evidenced reasons for augmenting physical therapists’ treatments, allowing more intense and diverse
therapy sessions for maintenance of skeletal muscle.
Supported by RC 1, 3, 4, 5
9. Aging, Inflammation and Exercise in Chronic Stroke (R01 AG030075 - 01A1: A. Ryan, Ph.D./ C.
Hafer- Macko, M.D.)
Inflammation is a risk factor for stroke and contributes to the progression of cardiovascular disease. Adipose
tissue is a major source of cytokine production and contributes to an inflammatory state associated with insulin
resistance. Moreover, inflammatory and anti-inflammatory skeletal muscle receptor activation affects intracellular signaling and muscle insulin sensitivity. Yet, there is a lack of understanding and exploration of the role
of tissue inflammatory changes in stroke. We have definitive preliminary data that stroke patients are
hyperinsulinemic and at increased risk for diabetes. Thus, our proposal seeks to study the mechanisms by
which treadmill training reduces inflammation and improves insulin sensitivity in normal glucose tolerant and
impaired glucose tolerant hemiparetic stroke patients.
Direct measurement of inflammatory modulators in adipose tissue and skeletal muscle would provide novel
information as to whether selected cytokines adversely affect insulin signaling in the skeletal muscle and are
associated with systemic insulin resistance in chronic stroke. Moreover, the studies proposed on the paretic leg
will permit us to examine the specific abnormalities attributable to the upper motor neuron injury from stroke,
while studies on the non-paretic leg will isolate the effects of disuse/deconditioning, and their respective
response to exercise training. This proposal is the first to investigate the mechanisms by which post-stroke body
composition abnormalities and physical inactivity interact to mediate inflammatory changes at the systemic and
tissue level (both skeletal muscle and adipose tissue) and propagate insulin resistance, as well as the potential
for exercise training to modify these abnormalities.
Supported by RC 1, 3, 4, 5
10. Testing Adaptive Physical Activity in Stroke (Pepper Pilot: K. Michael, Ph.D., RN, CRRN)
Testing Adaptive Physical Activity in Stroke is designed to determine whether adaptive physical activity (APA)
improves fitness, mobility function, daily step activity, and outcomes related to quality of life in individuals
with chronic stroke. Adaptive physical activity is an exercise model that combines elements of aerobic exercise
with balance and gait training in a socially reinforcing group setting. Individualized homework assignments
encourage integration of exercise into daily life routines.
Supported by RC 1, 3, 5
11. Adaptive Physical Activity for Chronic Stroke – APA (VA Merit - M. Stuart and R. Macko, M.D.)
The purpose of this study is to translate the Italian APA exercise model into a sustainable, evidence-based VA
community program of exercise for older adults with chronic stroke. Our short-term objectives are to test study
hypotheses using a Randomized Controlled Trial (RCT) with an Attention Control (also referred to in
subsequent sections as the "Sittercize" exercise program- active control comparison group). We will also
explore factors related to exercise adherence in a community program for chronic stroke survivors. Our longerterm objective is to disseminate this model to facilitate the development of a network of community-based
exercise programs for older adults with chronic stroke. In the RCT we propose to offer courses in Office on
Aging (OoA) Senior Centers, and a Veterans of Foreign Wars (VFW) hall (Yingling-Ridgely Post No. 7472).
At the conclusion of the research study, the OoA plans to continue offering APA-stroke courses. Through
partnership, the Veterans Health Administration (VHA) and the Administration on Aging (AoA) can potentially
replicate this model at the community level throughout the U.S. using local OoA Senior Centers, VFWs, as well
as other facilities that would increase community access for veterans.
Hypothesis # 1: When compared to a structured Attention Control (Sittercize), stroke participants in the APA
exercise program will demonstrate greater improvements in functional capacity (walking, balance etc...).
Hypothesis # 2: APA participants will also have greater improvements in free-living ambulatory activity
profiles and quality of life when compared to stroke participants in the Attention Control (Sittercize) exercise
program.
As translational research, our RCT has significant practical implications for program administrators. The
Attention Control we propose for this study is based on an exercise class that is already regularly offered at the
local OoA Senior Centers where we will conduct the study. The Attention Control course has some practical
operational advantages over the APA exercise program for center administrators in that it can safely
accommodate twice as many participants and does not require the level of supervision necessary for APA. Thus,
it is important to establish that APA-stroke has sufficient advantages to justify adding it to the curriculum.
Specific objectives of the proposed study are to:
1. Establish the safety, feasibility and efficacy of APA for stroke survivors when offered in a U.S. community
setting and compared to an Attention Control, using a RCT study design;
2. Improve our understanding of factors that influence exercise adherence and outcomes in community-based
exercise programs involving individuals in the chronic phase of stroke;
3. Disseminate policies, procedures, and detailed operating instructions to facilitate development of a network
of sustainable evidence-based community exercise programs for veterans with chronic stroke.
Results from this study will establish the safety and feasibility of the APA program for individuals with chronic
hemiparetic stroke. Further, the study will provide specific information about the treatment effects that can be
realized outside of the laboratory setting, and the translation of exercise-associated gains into everyday
behaviors. In collaboration with the Howard County Office and Aging Senior Centers and the University of
Maryland, Baltimore County, we have the opportunity to lay a foundation for further studies on the real-life
application of post-stroke exercise rehabilitation in community venues. Ongoing evaluation of treatment fidelity
will characterize the mobility training features and consistency of training in participants with various gait and
balance deficit profiles, thus setting the stage for larger dissemination in the United States
Supported by RC 1
12. Aging, Angiogenesis and Metabolic Responses to Aerobic Exercise (VA Career Development Award:
S. Prior, Ph.D.)
Diabetes and its associated complications affect more than 20 million Americans, and the prevalence of type 2
diabetes and impaired glucose tolerance rises dramatically with age such that 40% of Americans over age 60 are
affected. In older veterans, glucose metabolism may be affected by reduced skeletal muscle capillary supply,
which limits insulin, glucose, and oxygen delivery to skeletal muscle. Reduced capillary supply to skeletal
muscle is found in older individuals with impaired glucose tolerance (IGT) and we hypothesize that this is due
to: 1) reduced VEGF expression due to decreased insulin signaling through the p38 mitogen-activated protein
kinase (p38 MAPK), protein kinase B (Akt), and signal and transducer of transcription-3 (STAT3) pathways,
and 2) chronic inflammation evidenced by elevated tumor necrosis factor α (TNFα) expression. Further, we
hypothesize that reversal of a sedentary lifestyle through aerobic exercise (AEX) training will increase insulin
signaling and VEGF expression, as well as decrease inflammation, to increase capillary supply to skeletal
muscle, which contributes to improved glucose metabolism in older veterans with IGT.
These hypotheses will be tested through 2 aims:
1) Determine the mechanisms underlying reduced skeletal muscle capillarization in older veterans with IGT.
2) Determine the effect of AEX training-induced increases in skeletal muscle capillarization on glucose
metabolism in older veterans with IGT by acute (14-day) detraining after 6 months of AEX training.
Older (60-70 yrs) veterans with IGT (n=25) will be recruited, along with BMI-matched older (60-70 yrs; n=17)
and younger (30-40 yrs; n=17) veterans. We will compare all 3 groups to determine the mechanisms by which
skeletal muscle capillarization is reduced with older age and IGT, then study the effects of 6 months of AEX
training and 14 days of detraining in older veterans with IGT. At each time point, subjects will complete oral
glucose tolerance tests and 80 mU/m2/min hyperinsulinemic-euglycemic clamps to measure glucose utilization,
as well as basal and insulin-stimulated skeletal muscle biopsies to determine skeletal muscle capillary supply
(histochemistry), VEGF and TNFα gene and protein expression (qRT-PCR and ELISA), and insulin signaling
(Western blot). This study will determine the mechanisms by which the reversal of a sedentary lifestyle
improves angiogenesis and glucose metabolism in older veterans with impaired glucose tolerance. This will
potentially lead to a reduction in pharmaceutical and clinical costs related to type 2 diabetes and improve the
quality of life in older veterans by reducing the risk of type 2 diabetes and its cardiovascular disease
complications. Receipt of this VA Career Development Award will allow me to strengthen my basic molecular
biology and clinical research skills, and merge them to become a successful independent investigator in
translational aging research.
Supported by RC 1, 3
13. Translational Studies of a Novel Cardiovascular Disease Risk Factor Endothelial (R21: S. Prior,
Ph.D. Co-PI)
Cardiovascular disease (CVD) is the major cause of death in the US, which has resulted in an intense search for
CVD risk factors. Recent efforts have focused on novel CVD risk factors, as conventional risk factors may
explain <50% of CVD. Endothelial progenitor cells (EPCs) are one such novel CVD risk factor. Endurance
exercise training increases EPC number; however, most previous studies assessed only EPC numbers and
colony forming units, which represent a minimal characterization of EPC function. This proposal expands on
our previous work to study the cellular/molecular mechanisms underlying training-related changes in ex vivo
EPC function, using a cross-sectional comparison combined with exercise training in sedentary older adults and
training cessation in older endurance-trained athletes. We also will determine whether these training-induced
changes translate to improved in vivo endothelial function. To better characterize ex vivo EPC function we will
measure NADPH oxidase activity and expression, nitric oxide (NO) and reactive oxygen species (ROS) levels,
and tube formation in CD34+-derived putative EPCs, under both standard and atherogenic culture
environments.
Hypothesis #1 is, that on a cross-sectional basis, older athletes will have better ex vivo EPC function under
standard culture conditions and in response to an atherogenic culture environment than matched older sedentary
individuals. Our definition of “better” EPC function is lower ex vivo EPC NADPH oxidase expression/activity
and ROS levels and higher NO levels. We will also assess in vivo endothelial function to determine if it can be
used as a clinical index of ex vivo EPC function.
Hypothesis #2 is that exercise training in sedentary individuals will improve, and training cessation in older
athletes will worsen, ex vivo EPC function under standard culture conditions and in response to an atherogenic
environment and in vivo endothelial function. These results will allow us to validly conclude that exercise
training improves ex vivo EPC and in vivo endothelial function. We will then perform mechanistic studies by
manipulating NADPH oxidase activity and NO levels in cultures to assess the degree to which EPC function in
sedentary subjects can be improved by mimicking the intracellular EPC milieu evident in athletes. Our
Hypothesis #3 is that both inhibiting NADPH oxidase and increasing intracellular NO in putative EPCs from
sedentary individuals and from athletes after stopping training will improve ex vivo EPC function to levels
similar to those of trained athletes. This mechanistic approach will allow us to quantify the extent to which
exercise training effects on EPC function are a function of changes in EPC NADPH oxidase activity. Very few
studies have addressed the interaction between EPCs, as a novel CVD risk factor, and exercise training, and
virtually no studies have utilized human subjects and extended the studies to the cellular, metabolic, and
mechanistic levels. Thus, we are in a unique position to expand dramatically our understanding of the
mechanisms that underlie the benefits of exercise training on this novel CVD risk factor.
Supported by RC 3
14. Lateral Stability and Falls in Aging (R01 AG029510: M. Rogers, Ph.D., PT)
Falls and their consequences are among the major problems in the medical care of older individuals. The
goal of this research is to understand the neuromechanical (NM) mechanisms that underlie impaired balance
function and falls in older people in order to establish scientifically grounded therapeutic interventions for
improving balance and preventing falls.
Success in stepping sideways as a protective response to imbalance is problematic for many older
individuals. Lateral stepping responses are normally dependent upon high force, high speed usage of hip
abductor-adductor (AB-AD) muscles to effectively move the limbs in the medio-lateral (M-L) direction with the
correct timing and distance in order to prevent a fall from occurring. In older adults, difficulties with protective
stepping are characterized by the frequent use of multiple short recovery steps resembling stumbling with
dangerous collisions between the limbs when crossing one limb in front of the other to secure lateral balance.
We found that M-L stepping patterns and hip AB strength (joint torque) discriminate prospectively between
fallers and non-fallers confirming that these inappropriate balance responses are even more common among
older people who fall. Accordingly, we hypothesize that these detrimental changes in lateral stepping patterns
result from neuromechanical (NM) impairments in hip AB-AD joint moments of force (torques) that normally
regulate lateral balance stability during standing, stepping, and walking, and that these impairments are
attributable to changes in hip muscle composition (reduced muscle area and increased intramuscular fat).
Furthermore, we propose that, in contrast with the established age-associated changes in leg flexor and extensor
muscle groups, similar changes in hip AB-AD muscle performance and muscle composition may be even
greater because older adults less often engage in activities that require strenuous hip abduction or adduction
such as during single limb weight bearing tasks and moving sideways. The constellation of age-associated
changes in physiological and biomechanical function involving lateral balance factors is likely at the source of
the directionally-specific vulnerability to lateral instability that increases the risk of falls and their
consequences, particularly, hip fracture for many older individuals.
Specific Aims:
1. Identify the waist-pull balance perturbation magnitude (pulling displacement, velocity, acceleration)
where protective stepping responses transition to less effective balance recovery patterns (balance tolerance
limit), and then assess whether the balance tolerance limit and associated stepping patterns discriminate
between subjects at high and low risk of falls.
H1. A balance tolerance limit exists where protective stepping patterns worsen and become more
problematic for balance recovery as indicated by: a) increased use of multiple additional recovery steps, b)
shorter first step length, and c) greater incidence of crossover steps with collisions between the limbs.
H2. Compared with individuals at lower fall risk, subjects at higher risk of falls will have a lower balance
tolerance limit where protective stepping patterns become less effective for stabilizing balance.
2. Evaluate a) the maximum hip AB-AD joint torque and power, and b) hip AB-AD muscle area and muscle
attenuation (intramuscular fat) determined by computed tomography (CT).
H. 3. A lower balance tolerance limit and associated decrements in protective stepping performance will be
accompanied by worse muscle strength, mass, and quality as indicated by lower maximum hip AB-AD joint
torque and power, smaller muscle area, and increased intramuscular fat.
H. 4. Maximum hip AB-AD torque and power, muscle area, and muscle attenuation (intramuscular fat) will
discriminate between individuals at high and low risk for falls.
In a secondary aim we will assess whether the directional vulnerability to lateral instability experienced by
many older individuals is linked with a disproportionate decline in M-L hip AB-AD muscle performance and
composition compared with flexor and extensor anterior-posterior compartment muscle groups. We will
compare the muscle strength (joint torque and power) and muscle composition (muscle area and intramuscular
fat) of major hip and knee flexor-extensor muscle groups involved with forward-backward balance control with
the hip AB-AD muscles involved with lateral balance stability. We propose that, in contrast with the established
age-associated changes in leg flexor and extensor muscle groups, similar changes in hip AB-AD muscle
composition may be even greater because older adults tend not to or rarely engage in activities that require
strenuous use of hip abduction or adduction muscles such as during single limb weight bearing tasks and
vigorous sideways movement.
Supported by RC 1, 2, 3, 5
15. Neurocognition and Functional Performance in Older Veterans with CKD (VA Merit: S. Seliger,
M.D./L. Katzel, M.D., Ph.D.)
Chronic Kidney Disease (CKD) affects 1 out of 5 older adults in the US including more than 400,000 older
veterans yet is often unrecognized by affected individuals and even their healthcare providers. Older adults
with CKD suffer from a markedly higher risk of cognitive and physical dysfunction, including a 40% greater
risk of dementia and a 75% greater risk of physical frailty. The factors which account for this risk are unclear;
however, recent neuroimaging investigations suggest a greatly increased burden of covert brain pathology in
association with CKD and reduced kidney function. Outside the context of CKD, these neuroimaging findings
of subclinical ischemic brain disease - silent brain infarcts, white matter hyperintensities, atrophy, and
hypoperfusion - are associated with reduced cognitive and physical function. However, there has been no
formal statistical evaluation of subclinical ischemic brain disease as a mediator of the relations of CKD to
physical and cognitive function, nor any investigations of the patterns of cognitive and physical dysfunction in
older adults with CKD.
We hypothesize that older veterans with CKD suffer from a greater burden of subclinical ischemic disease of
the brain, which results in impaired neurocognition and physical function. In this revised proposal, we will
conduct an observational cohort study of stroke-free community-dwelling older veterans (ages 60-85) with
CKD not requiring dialysis (N=150, evenly distributed among mild, moderate and severe CKD), and a control
group without CKD but frequency-matched on the common co-morbid conditions diabetes, hypertension and
cardiac disease (N=50). We will obtain quantitative measurements of 1) kidney disease and function (including
albuminuria and the renal biomarker cystatin C), 2) ischemic brain disease using MRI, 3) physical function and
performance, and 4) multiple domains of neurocognitive function. The overall aims are to estimate the
association of CKD and renal function measures with MRI-defined subclinical ischemic brain disease and
cognitive and physical function. Multivariate analyses will be employed to identify patterns of functional
deficits and alterations of brain structure in CKD. Structural equations models (SEM) will examine whether
subclinical ischemic brain disease mediates the relations of CKD and associated renal function measures to
neurocognition and physical function after accounting for major co-morbid conditions including hypertension,
diabetes, and cardiac disease. Results of this investigation will be of critical importance in the development of
methods to detect and ultimately prevent functional deficits among older adults with CKD, a highly prevalent
and rapidly growing population.
Specific Aim #1: To examine the association of CKD and individual biomarkers of renal dysfunction with
subclinical ischemic brain disease, neurocognitive function, and physical function among community-dwelling
stroke- and dementia-free older veterans.
Specific Aim #2: Using structural equations modeling (SEM), examine whether a greater burden of subclinical
ischemic brain disease mediates the relation of CKD and its biomarkers to decreased cognitive and physical
function among older veterans.
Supported by RC 1, 3, 5
16. Veterans with Stroke Translating Exercise Programs (VA Merit: M. Shaughnessy, Ph.D., RN,
CRNP/F. Ivey, Ph.D.)
This four year Merit Review proposal directly compares the efficacy of two markedly different exercise models
in veteran stroke survivors, within the context of an overall cardiovascular risk factor reduction program. We
will gain insight into how these programs are translated into VA community settings, as well as the ideal order
of initiation when participants are exposed to both interventions in a counterbalance manner over 12 months.
We hypothesize that initiating the proposed 12-month cross-over intervention with higher intensity treadmill
training (HI-TM) (months 0-6) followed by a lower intensity group exercise program (LILI) (months 6-12) will
result in the largest long-term impact on functional and behavioral outcomes. Specifically, we propose that HITM will establish a baseline level of cardiovascular fitness and endurance such that that the balance and gait
training in LILI can be optimally applied for the greatest benefit in months 6 through 12. Conversely, the
opposing intervention pattern of LILI followed by HI-TM may produce the greatest cardiometabolic adaptations
by month 12, given that that stroke survivors in this group will start HI-TM at month 6 with a higher level of
baseline functional competence.
The Specific Aims are:
(1) Directly compare the effects of 6-months HI-TM, LILI and EC (education control) regimens on functional,
cardiometabolic, behavioral, and quality-of-life outcomes in disabled veteran stroke survivors.
(2) Assess whether order of implementation impacts gains in each outcome category during a cross-over period
to 1 year.
(3) Compare the durability and continuation of all outcome gains in cohorts performing ongoing formal centerbased training versus cohorts undergoing only home-based exercise during months 12-18.
The proposal consists of eight phases that are estimated to take each treatment arm cohort approximately 20 - 21
months to complete. During phase 1 (ongoing) we will screen and consent chronic stroke patients. Phase 2 will
consist of baseline testing that includes assessments of peak aerobic capacity, oral glucose tolerance,
ambulatory function, balance, free-living physical activity, self-reported physical activity, lifestyle behaviors,
self-efficacy/ outcome expectations for exercise, stage of readiness to change exercise behavior, functional
status and perceived quality of life. Volunteers are then randomized to either HI-TM, LILI or EC for 6 months
(phase 3). All groups, including EC, will receive evidence-based education and counseling for adherence to the
American Stroke Association's guidelines for prevention of secondary stroke. In Phase 4, all baseline testing
and analyses are repeated. In Phase 5, those in the two treatment arms commence with an additional 6-month
cross-over period with all measures repeated at 12 months (Phase 6). Finally, Phase 7 relates to exploratory Aim
3 (suggested by reviewers) during which half of participants continue formal center-based exercise training for
comparison at month 18 (Phase 8) with those who discontinue formal training in favor of home-based exercise
recommendations. Aim 3 will provide important preliminary information on the exercise requirements for
adding to or durably maintaining outcome gains over an extended period after disabling stroke.
The work proposed in this Merit Award addresses a number of factors that will help define new evidence for
rehabilitation models within the VHS. Current methods of stroke rehabilitation do not effectively prevent or
reverse changes in metabolic fitness, function, and declining activity patterns, causing decrements to both
physiological and psychological health.
The proposed study will provide foundational evidence for translating exercise models into the community
where it has the greatest chance to benefit the largest number of disabled veterans who are most in need of help.
This may ultimately change the current standard of care by providing evidenced-based reasons for dramatically
altering the way disabled veteran stroke survivors are counseled and transitioned following completion of
conventional therapy.
Supported by RC 1, 3, 5
C.
PILOTS (Pilot Projects – Year 01 (1994) to Present )
Year 01 (1994-1995)
Effects of Exercise on Blood Pressure, Hyperinsulinemia and Renal Function in the Elderly
Donald R. Dengel, Ph.D., Research Associate (410) 605-7000 x5446 (Andrew Goldberg, M.D., Matthew Weir,
M.D., Mentors)
Exercise Rehabilitation Programs for the Treatment of Claudication Pain
Andrew W. Gardner, Ph.D., Assistant Professor (410) 605-7000 x5426 (Eric Poehlman, Ph.D., Mentor)
Effect of Weight Loss and Exercise Training on Lipoprotein Lipid Metabolism in Elderly with
Atherogenic LDL Phenotype
Leslie I. Katzel, M.D., Ph.D., Assistant Professor (410) 605-7000 x5422 (Andrew Goldberg, M.D., Mentor)
Costs of Congestive Heart Failure among the Elderly
Ernest Moy, M.D., MPH, Assistant Professor (410) 328-6598 (James Hudson, M.D., Mentor)
The Effects of Strength Training on Insulin Sensitivity and Glucose Tolerance in Post-Menopausal
Women with Impaired Glucose Tolerance
Alice Smith Ryan, Ph.D., Research Fellow (410) 605-7000 x5449 (Dariush Elahi, Ph.D., Mentor)
Year 02 (1995-1996)
Cognitive Functioning of Hip Fracture Patients in the Hospital: Components, Predictors, Trajectories,
Outcomes, and Implications for Intervention
Ann L. Gruber-Baldini, Ph.D., Research Associate (410) 706-2444 (Jay Magaziner, Ph.D., M.S. Hyg., Mentor)
Aerobic Exercise in the Elderly Stroke Population
Richard F. Macko, M.D., Assistant Professor (410) 605-7000 x0063 (Andrew Goldberg, M.D., Mentor)
Effects of Aerobic Exercise in Endogenous Fibrinolysis in Elderly Patients with Intermittent Claudication
and Stroke
Lois Killewich, M.D., Ph.D., Assistant Professor (410) 605-7229 (William Flinn, M.D. and Andrew Goldberg,
M.D., Mentors)
Assessment of Leg Perfusion in Intermittent Claudication
Andrew Gardner, Ph.D., Research Assistant Professor (410) 605-7000 x5426 (William Flinn, M.D., Mentor)
Year 03 (1996-1997)
The Effect of Risk Factor Modification (Diet, Weight Loss, Smoking Cessation, Exercise) on
Endothelium-Dependent Brachial Artery Vasoactivity in Older Men and Women.
Mary Corretti, M.D., Assistant Professor (410) 328-6190 (Stephen Gottlieb, M.D., Leslie Katzel, M.D., Ph.D.,
Mentors)
The Impact of Computer-Assisted Data Collection in a Geriatric Population
Roopak Manchanda, M.S. (410) 605-7000 x5430 and Mitchell Rosen, Ph.D. (410) 605-7119 (Douglas
Bradham, Dr.P.H., Mentor)
Lower Extremity Strength in Vascularly Disabled Individuals: Peripheral Arterial Disease and Stroke
Kenneth Silver, M.D., Associate Professor (410) 328-6484 (Andrew Goldberg, M.D., James Hagberg, Ph.D.,
Mentors)
The Effect of Exercise on Recovery of Function Following Hip Fracture
Perry Colvin, M.D., Assistant Professor (410) 605-7217 (Jay Magaziner, Ph.D., Mentor)
Year 04 (1997-1998)
The Effect of Exercise on Recovery of Function Following Hip Fracture
Perry Colvin, M.D., Assistant Professor (410) 605-7217 (Jay Magaziner, Ph.D., Mentor)
The Effect of Risk Factor Modification (Diet, Weight Loss, Smoking Cessation, Exercise) on
Endothelium-Dependent Brachial Artery Vasoactivity in Older Men and Women.
Mary Corretti, M.D., Assistant Professor (410) 328-6190 (Stephen Gottlieb, M.D., Leslie Katzel, M.D., Ph.D.,
Mentors)
Electromagnetic Motor Evoked Potentials (MEPs) as a Prognostic Measure of Functional Outcomes in
Stroke Patients.
Gerald Smith, Ph.D., P.T., Assistant Professor (410) 706-7720 (Mary Rodgers, Ph.D., PT, Mentor
Year 05 (1998-1999)
Muscle Fiber Plasticity in Hemiparetic Patients after an Aerobic Exercise Program
Patrick DeDeyne, Ph.D., MPT, Assistant Professor (410) 706-2703 (Andrew Coggan, Ph.D., Mentor)
Analysis of Cardiac Na/Ca Exchanger During Aging
Abdul Ruknudin, Ph.D., Research Assistant Professor (410) 706-6240 (John Lederer, M.D., Ph.D., Mentor)
Upper Extremity Training in Stroke Patients: A Feasibility Study
Sandra McCombe-Waller, M.S., Clinical Instructor (410) 706-7720 (Jill Whitall, Ph.D., Mentor)
Year 06 (1999-2000)
Neuroplasticity and Upper Extremity Training in Stroke Patients
Larry Forrester, Ph.D., PT, Associate Professor (410) 706-5212 (Jill Whitall, Ph.D., Daniel Hanley, M.D.,
Gerald Smith, Ph.D., PT, Mentors)
Year 07 (2001-2002)
The Construct of a Hip Fracture-Specific Functional Test and Feasibility of a New Training Program.
Gad Alon, Ph.D., PT, Associate Professor (410) 706-7733 (Perry Colvin, M.D., Jay Magaziner, Ph.D., M.S.
Hyg., Mentors)
Short-term Neural Adaptations with Treadmill Training in Chronic Hemiparetic Stroke Patients.
Larry Forrester, Ph.D., Assistant Research Professor/Research Associate (410) 706-5212 (Daniel Hanley, M.D.,
Richard Macko, M.D. Mentors)
Development of a Rodent Model Using Aerobic Exercise as Rehabilitative Intervention after Focal
Cerebral Ischemia.
Daniel Hanley, M.D., Professor (Johns Hopkins University) (410) 614-5185
Peripheral Arterial Occlusive Disease, Cognition, and Magnetic Resonance Abnormalities in Older
Adults.
Shari Waldstein, Ph.D., Assistant Professor (410) 455-2567 (Leslie Katzel, M.D., Ph.D., Eliot Siegel, M.D.,
David Lefkowitz, M.D., Abraham Obuchowski, M.D., Mentors)
Year 08 (2002-2003)
Muscle Protein Profile in Patients with Stroke
Patrick G. DeDeyne, Ph.D., M.P.T., Associate Professor (410) 706-2703 (Richard Macko, M.D., Mentor)
Progressive Rate Training (PRT) Post Stroke
Carwile LeRoy, M.D., Associate Investigator/Fellow (410) 605-7000 ext 5452 (Richard Macko, M.D., Mentor)
Assessing Treatment Fidelity in the Pepper Center: Enhancing Intervention Research
Denise Orwig, Ph.D., Assistant Professor (410) 706-2406 (Jay Magaziner, Ph.D., M.S. Hyg., Mentor)
Medical Cost Implications of Changes in Functional Status
Bruce Stuart, Ph.D., Professor (410) 706-5389
Central Motor Control Mechanisms Associated with Hand Dominance and Their Adaptability to
Unilateral and Bilateral Training
Sandra McComb Waller, MS, PT, Assistant Professor (410) 706-0787 (Jill Whitall, Ph.D., Mary Rodgers,
Ph.D., Mentors)
Year 09 (2003-2004)
Impedance-Controlled Ankle Robotics: A Novel Technology for Gait Rehabilitation after Stroke
Larry Forrester, Ph.D., Assistant Professor (410) 706-5212 (Richard Macko, M.D., Igo Krebs Ph.D.,
Christopher Bever, M.D., Mentors)
Age, Lifestyle, Muscle Mechanisms in Insulin Resistance (Training Only)
Lyndon Joseph, Ph.D., Assistant Professor, (410) 605-7000 ext 5783 (Alice Ryan, Ph.D., Andrew Goldberg,
M.D., Mentors)
Morphometrical and Volumetrical Characteristics of the Lesioned Brain as Predictors of Therapeutic
Benefits of BATRAC and AEX
Andreas Luft, M.D., Assistant Professor, University of Tübingen, Germany +49 7071 967853 (Daniel Hanley,
M.D., Mentor)
Skeletal Muscle Size and Performance in HIV and Individuals of Differing Functional Status
David Russ, P.T., Ph.D., Assistant Professor, (410) 706-7165 (Les Katzel, M.D., Ph.D., Andrew Goldberg, M.D.)
Year 10 (2004-2005)
Adipose Tissue Production of Inflammatory Cytokines: Cellular Sources and Changes with Age
Jacob Blumenthal, M.D., Assistant Professor, (410) 605-7000 ext 5426 (Susan K. Fried, Ph.D. Andrew P.
Goldberg, M.D.)
The Effects of Exercise on Renal Function as Measured by Cystatin C Versus Creatinine-based Estimates
of Glomerular Filtration Rate
Jeffrey Fink, M.D., Associate Professor of Medicine, (410) 605-7000 ext 5280 (Les Katzel, M.D., Ph.D.,
mentor)
Does side of Stroke Affect Central Motor Control Mechanisms in Response to Short-term Unilateral
Versus Bilateral Training?
Sandy McCombe Waller, Ph.D., PT, Assistant Professor, (410) 706-0787 (Jill Whitall, Ph.D., Daniel Hanley,
M.D.)
The Effects of Resistive Training on Muscle Atrophy and Insulin Sensitivity in Hemiparetic Stroke
Patients
Alice S. Ryan, Ph.D., Associate Professor, (410) 605-7851 and Fred Ivey, Ph.D., Assistant Professor, (410)
605-7297 (Richard Macko, M.D., Andrew P. Goldberg, M.D.)
Exercise Rehabilitation in Parkinson Disease
Frank Skidmore, M.D., Assistant Professor, (410) 299-1880 cell phone (Richard F. Macko, M.D., Lisa M.
Shulman, M.D., William J. Weiner, M.D.)
Year 11 (2005-2006)
SAA Reduction as a Beneficial Mechanism of Weight Loss by Exercise
Da-Wei Gong, M.D., Ph.D., Assistant Professor (410) 706-1672 (Andrew P. Goldberg, M.D., Alice Ryan,
Ph.D.)
Feasibility Study for the Measurement of Lower Extremity Muscle Strength, Muscle Composition and
Cardiovascular Fitness Following Hip Fracture
Ram Miller, MDCM, MSc, Assistant Professor (410) 706-3907 (Jay Magaziner, Ph.D., Alice Ryan, Ph.D.,
Richard Macko, M.D., Charlene Hafer-Macko, M.D.)
Aging and HIV
Kris Ann Oursler, M.D., Associate Professor (410) 328-6056 (Les Katzel, M.D., Charlene Hafer-Macko, M.D.)
Effects of Ambulatory Exercise Training on Risk Factors for Sudden Cardiac Death in Stroke Patients
Eric Rashba, M.D., Associate Professor (410) 328-6056 (Richard Macko, M.D., Frederick Ivey, Ph.D.)
Cerebral Hypoperfusion and Cognitive Dysfunction in Chronic Kidney Disease (CKD)
Stephen Seliger, M.D. MS, Assistant Professor (410) 605-5231 (Shari Waldstein, Ph.D., Les Katzel, M.D.,
Ph.D., Jeffrey Fink, M.D., MS, Eliot Siegel, M.D.)
Year 12 (2006-2007)
The Effect of Treadmill Training on Recovery of Lower Extremity Function and Inflammatory
Cytokines in Hip Fracture Patients.
Ram Miller, MDCM, MSc, Assistant Professor (410) 706-3907 (Jay Magaziner, Ph.D., Alice Ryan, Ph.D.,
Richard Macko, M.D., Charlene Hafer-Macko, M.D.)
Mechanisms of Cellular Regeneration and Repair in the Functional Recovery of Skeletal Muscles from
Older Animals Following Eccentric Injury.
David Russ, P.T., Ph.D., Assistant Professor, (410) 706-7165 (Les Katzel, M.D., Ph.D., Andrew Goldberg, M.D.)
Short-term adaptations in paretic and lower extremity motor control after stroke: Bilateral coupled
robots vs. passive manual exercise.
Larry Forrester, Ph.D., Assistant Professor (410) 706-5212 (Richard Macko, M.D., Igo Krebs Ph.D.,
Christopher Bever, M.D., Mentors)
Year 13 (2007-2008)
Adaptive Physical Activity in Hemiparetic Stroke
Kathleen Michael, Ph.D., Assistant Professor (410) 605-4844 (Richard Macko, M.D., Andrew Goldberg, M.D.,
Mentors)
Effects of Aerobic Exercise Training on VEGF, Angiogenesis and Glucose Metabolism in Older Adults
Steven Prior, Ph.D. Assistant Professor (410) 605-4129 (Alice Ryan, Ph.D., Andrew Goldberg, M.D., Heidi
Ortmeyer, Ph.D., Mentors)
Immunologic Dysfunction in Elderly Subjects who undergo Aerobic Exercise Rehabilitation
Wilbur Chen, M.D., Assistant Professor (410) 706-5328 (Andrew Goldberg, M.D., Alice Ryan, Ph.D.,
Mentors)
The Effect of Home-Based Exercise Training on Recovery of Lower Extremity Function and
Inflammatory Cytokines in Hip Fracture Patients
Ram Miller, M.D.C.M., Assistant Professor (410) 706-2406 (Jay Magaziner, Ph.D., Les Katzel, M.D., Ph.D.,
Mentors)
Resistive Training and Skeletal Muscle Insulin Action in Hemiparetic Stroke Patients
Alice S. Ryan, Ph.D., Professor, (410) 605-7851 and Fred Ivey, Ph.D., Assistant Professor, (410) 605-7297
(Richard Macko, M.D., Mentor)
Year 14 (2008-2009)
Endothelial Function and Cognitive Dysfunction in Chronic Kidney Disease
Afshin Parsa, M.D., Ph.D., Assistant Professor, (410) 706-6445 (Les Katzel, M.D., Ph.D., Mentor)
Hip Muscle Composition: Relationships with Neuromechanical Performance, Lateral Stability, and Risk
of Falls in Older Adults
Mark Rogers, Ph.D., P.T. Professor, (410) 706-0841 (Andrew Goldberg, M.D. and Alice Ryan, Ph.D. Mentors)
UM-OAIC & MERCE Joint Pilot Collaboration
Assessment of Motor System Connectivity in Stroke Rehabilitation
Alan McMillan, Ph.D., Research Associate, (410) 328-6104 (Jill Whitall, Ph.D., Mentor)
Year 15 (2009-2010)
Impact of Inflammatory Bowel Disease and Aging on Body Composition and Functional Performance
Raymond Cross, M.D., MS, Associate Professor, (410) 706-3387 (Les Katzel, M.D., Ph.D., and Alice Ryan,
Ph.D., Mentors)
The Effects of Aging on Airway Smooth Muscle Contraction and Relaxation
Deepak Deshpande DVM, Ph.D., Assistant Professor, (410) 706-1070 (Andrew Goldberg, M.D., Mentor)
Task-Oriented Exercise and Behavioral Intervention to Promote Activity in Stroke
Kathleen Michael Ph.D., RN, CRRN, Assistant Professor, (410) 706-0142 (Richard Macko, M.D. and Andrew
Goldberg, M.D., Mentors)
UM-OAIC & MERCE Joint Pilot Collaboration
Cortical and Biomechanical Dynamics of Lower Extremity Robot Assisted Training at Different Levels of
Motivational Incentive Implications for Stroke Survivors
Ronald Goodman, Ph.D., Research Fellow, (410) 605-7000 ext. 4349 (Richard Macko, M.D. and George
Wittenberg, M.D., Ph.D., Mentors)
Myasthenia Gravis Exercise Program to Increase Physical Activity and Fitness and Reduce
Cardiovascular Risk
Charlene Hafer-Macko, M.D., Associate Professor, (410) 328-3100 (John Sorkin, M.D., Ph.D. Mentor)
Plasticity, Kinetics and Kinematics of Bilateral Reaching Therapy in Chronic Stroke
Lauren Jones-Lush, Ph.D., Assistant Professor, (410) 706-5490 (George Wittenberg, M.D., Ph.D., Mentor)
Year 16 (2010-2011)
Role and Mechanism of Exercise Induced Facilitation of Recovery after Experimental Traumatic Brain
Injury
Alan Faden M.D., Professor, (410) 706-4205 (Richard Macko, M.D., Mentor)
Pilot Study of Prehabilitation Prior to Elective Surgery in Older Adults
Ram Miller M.D., CM, Assistant Professor, (410) 706-2406 (Jay Magaziner, Ph.D., MsHyg, Mentor)
Effect of a Progressive, Adaptive Physical Activity Regimen on Functional Outcomes and
Musculoskeletal Composition in Elderly Survivors of Critical Illness
Giora Netzer, M.D., MSCE, Assistant Professor, (410) 706-3344 (Michael Terrin, M.D., CM, MPH, Mentor)
Functional and Metabolic Benefits of Rehabilitation in HIV
Kris Ann Oursler, M.D., Assistant Professor, (410) 605-7000 ext.7194 & Heidi Ortmeyer, PhD, Assistant
Professor, (410) 605-7000 ext. 5419 (Charlene Hafer-Macko M.D., Alice Ryan Ph.D., Andrew Goldberg, M.D.,
Mentors)
UM-OAIC & MERCE Joint Pilot Collaboration
Does Strength Training Improve Balance Training in Older Adults?
Brock Beamer, M.D., Assistant Professor. (410) 605-7000 ext. 4870 (Andrew Goldberg, M.D., Mark Rogers
Ph.D, PT, Mentors)
III. CAREER DEVELOPMENT
UM-OAIC Career Development Awardees And Subsequent Funding
Peter Vaitkevicius, M.D., Assistant Professor Gerontology and Cardiology (Moved to Johns Hopkins
University in 1994; Present position: Internal Medicine Physician, Harper University Hospital)
Ernest Moy, M.D., MPH, Assistant Professor, Internal Medicine, University of Maryland Baltimore (Present
Position: Lead Staff, Agency for Healthcare Research and Quality)
Andrew Gardner, Ph.D., Assistant Professor, Gerontology, University of Maryland Baltimore (R01 awarded
in 2000; Present position: Professor, Department of Kinesiology, University of Oklahoma)
Lois Killewich, M.D., Ph.D., Assistant Professor, Surgery (Vascular Medicine) (Present position: Associate
Professor, University of Texas, Galveston)
Barbara Bartman, M.D., MPH, Assistant Professor, Internal Medicine, University of Maryland Baltimore
(Present position: Medical Officer in the Center for Outcomes and Evidence at AHRQ)
Richard Macko, M.D., Professor, Neurology, Medicine/Gerontology, Physical Therapy & Rehabilitation
Science University of Maryland School of Medicine & Baltimore VA Medical Center; Director, Academic
Rehabilitation Program, UM-SOM , & the Maryland Exercise & Robotics Center of Excellence (MERCE)
 R29 Award (1996)
 RCDA awarded (1997)
 VA Research Enhancement Award Program (REAP) - Clinical and Translational Research in Stroke –
Disability Reduction and Disease Prevention
 VA RR&D - VA Center of Excellence: Task-Oriented Exercise and Robotics in Neurological Disease
 Michael J. Fox DOPA 2006RFA - Treadmill Training and Gait Related Disability in Parkinson’s Disease
 VA RRDC- Cardiovascular parameters for lokomat training in chronic incomplete spinal cord injury
 VA RR&D- VA Center of Excellence: Community Translational Supplement Grant
 NIH RO1- Exercise models to improve cardiometabolic health and function after stroke (pending)
 NIH RO1- Effects of early exercise on muscle and cardiovascular health after stroke (pending)
Larry Forrester, Ph.D., Associate Professor, Department of Physical Therapy, University of Maryland
Baltimore
 VA Advanced Career Development Award: Development of Ankle Robot Model with Treadmill
Training in Chronic Stroke.)
 CDA VA B3390K – Development of an Ankle Robot with Treadmill Training in Chronic Stroke Research ;
 VA MERCE award- Task-Oriented Exercise and Robotics in Neurological Disease
 VA RR&D Center of Excellence: Task-oriented exercise and robotics in neurological disease.
 Co-Investigator on VA MERCE
 VA REAP - “Modular Lower Extremity Robotics Assisted Exercise after Stroke”
 PI for VA MERCE Human Performance & Neural Plasticity Core
 Advanced Research Career Development Award, Department of Veterans Affairs: Rehabilitation
Research and Development Service (2004-2007). Development of an Ankle Robot Module with
Treadmill Training in Chronic Stroke. (PI).
 NIH Claude D. Pepper Older Americans Independence Center Pilot Grant (2004-2005). ImpedanceControlled Ankle Robotics: A Novel Technology for Gait Rehabilitation after Stroke
 VA RR&D Plasticity Center of Excellence Pilot Study (2005-2006): Adaptations in cortical function
induced by short-term robot-assisted training of foot movements in chronic stroke survivors.


VA Merit- Ankle robotics training after stroke: Effects on gait and balance
University of MD College Park Seed Grant- Non-invasive real-time neural decoding of walking from
EEG activity
Marianne Shaughnessy, Ph.D., CRNP, Associate Director for Education/Evaluation, Baltimore VA GRECC;
Assistant Professor, School of Nursing, University of Maryland Baltimore
 Maryland Statewide Health Network Grant through the Maryland Cigarette Restitution Fund Program
Exercise and Diet Programs to Improve Cardiovascular Health in a West Baltimore Faith Community,
 VA RR&D- VA Center of Excellence Pilot: Task-Oriented and Robotics in Neurological Diseases (PI
Macko)
 VA- Geriatric Research, Education and Clinical Center (GRECC) (PI Goldberg)
 VA Merit- Strength Training for Skeletal Muscle Adaptation after Stroke (Co-PI Ivey)
Denise Orwig, Ph.D., Assistant Professor, Department of Epidemiology and Preventive Medicine, University
of Maryland Baltimore
 NHLBI via UMDNJ: functional Outcomes in CV Patients Undergoing Surgical Hip Repair “FOCUS”
(U01 Co-I J. Carson)
 Sequelae of Hip Fracture in Men: An Epidemiologic Study (R37Diversity Supplement, Co-I with M.
Matheny)
 Multinational, multicenter, double-blind, randomized, placebo-controlled, parallel group study assessing
the efficacy of intravenous zoledronic acid in preventing subsequent osteoporotic fractures after a hip
fracture “HORIZON-RFT” (Co-I with K. Lyles)
 Feasibility of a 16-week multi-component intervention 2 months post hip fracture (Co-I with L.
Fredman)
 Biological Pathways of Acute and Chronic Stress in Aged Hip Fracture Caregivers (R01 Co-I with L.
Fredman)
Frederick Ivey, Ph.D., Assistant Professor, Department of Medicine, University of Maryland Baltimore
 NIH/NIA KO1 AG 091242. Effects of Exercise on Endothelial Function in Chronic Hemiparetic Stroke
Patients
 VA Merit - Effects of Exercise on Endothelial Function in Stroke Patients
 VA Merit - Strength Training for Skeletal Muscle Adaptation after Stroke (Co-PI Shaughnessy)
Carwile LeRoy, M.D., Assistant Professor, Department of Medicine, University of Maryland Baltimore
(current position, private practice)
Jacob Blumenthal, M.D., Assistant Professor, Department of Medicine, University of Maryland Baltimore
 VA-Advanced Research Career Development Award – Cytokines, Central Obesity and Fat Metabolism in
Aging;
 VA Merit- using MOVE! With Seriously Mentally Ill (PI Goldberg)
 VA Merit Review- Exercise, Inflammation and Prothrombotic Modulators in the Elderly (PI Ryan)
 VHA- Patient-Centric Alternatives to Institutional Extended Care Project- Decreasing Barriers to Care for
Veterans with Dementia
Eun-Shim Nahm, Ph.D., RN, Associate Professor, Department of Organizational Systems and Adult Health,
School of Nursing, University of Maryland Baltimore
 1R21AG026013-01A1
 Effects of a Hip Fracture Prevention Website for Seniors


Effects of a Hip Fracture Prevention Website for Seniors “Education for Consumers and Healthcare
Professionals” (Moderator: Nahm, E.-S.)
The 9th International Congress on Nursing Informatics, Korea, June 9 – 14, 2006.
R21 AG029578 - Feasibility of a Theory-Based Online Hip Fracture Resource Center for Caregivers
Kris Ann Oursler, M.D., Assistant Professor, HIV Medicine, University of Maryland Baltimore
 NIA K23 Aging and Physical Functioning in HIV (PI Oursler)
 NIH RO1 (PI: Freidberg) Assessment of Cardiac Tests in Vacs Exercise Study
 AARA Supplement- Persistent fatigue in well-controlled older HIV-infected patients: Investigation of
skeletal muscle oxidative function (Pending)
Federico Villagra, Ph.D., PT, Assistant Professor, Department of Physical Therapy and Rehabilitation
Sciences, University of Maryland Baltimore. (Subsequent position Accepted faculty position in Spain June 29,
2007)
Sandy McCombe Waller, Ph.D., Assistant Professor, Department of Physical Therapy and Rehabilitation
Sciences, University of Maryland Baltimore
 McCombe Waller, S., & Whitall, J. (March 2004) "Cortical Inhibition and Facilitation in Unilateral
versus Bilateral Movement Tasks and Adaptability to Training in Nondisabled Adults" International
Conference on Motor Control, Barcelona,
 McCombe Waller, S., (2004) Central Motor Control Mechanisms in Left and Right Handed Adults
 Presented at the First Neuroplasticity and Rehabilitation Science Conference, Ftan , Switzerland.
 McCombe Waller., S., (2005) Central Motor Excitability with Unilateral Dominant, Unilateral
Nondominant and Bilateral Movement Tasks in Left and Right Handed Adults, Combined Sections
Meeting for APTA, New Orleans, LA.
 OAIC pilot- Does side of stroke affect central motor control mechanisms in response to short-term
unilateral versus bilateral training?
 R21 - Combining Bilateral and Distal Arm Training to Promote Arm and Hand Recovery in Patients
with Chronic Hemiparesis
Kathleen Michael, Ph.D., RN, CRRN, Assistant Professor, Department of Organizational Systems and Adult
Health, School of Nursing, University of Maryland Baltimore
 NIH Claude D. Pepper Older Americans Independence Center Pilot Grant (2009-2010). Task Oriented
Exercise and Behavioral Interventions to Promote Activity in Stroke (PI Goldberg)
IV. PUBLICATIONS
2010-2011
Adachi JD, Lyles KW, Colon-Emeric CS, Boonen S, Pieper CF, Mautalen C, Hyldstrup L, Recknor C,
Nordsletten L, Moore KA, Bucci-Rechtweg C, Su G, Eriksen EF, Magaziner JS. Zoledronic acid results in
better health-related quality of life following hip fracture: the HORIZON-Recurrent Fracture Trial. Osteoporos
Int2011 Jan 20. [Epub ahead of press] [PMID: 21249332] (RC 1)
Boonen S, Black DM, Colon-Emeric CS, Eastell R, Magaziner JS, Eriksen EF, Mesenbrink P, Haentjens P,
Lyles KW. Efficacy and safety of a once-yearly intravenous zoledronic acid 5 mg for fracture prevention in
elderly postmenopausal women with osteoporosis aged 75 and older. J Am Geriatr Soc2010 Feb;58(2):292-9.
[PMID: 20070415] (RC 1)
Chen WH, Cross AS, Edelman R, Sztein MB, Blackwelder WC, Pasetti MF. Antibody and Th1-type cellmediated immune responses in elderly and young adults immunized with the standard or a high dose influenza
vaccine. Vaccine 2011 Apr 5; 29(16):2865-73. [PMCID: 3070775] (RCDC)
Colon-Emeric C, Nordsletten L, Olson S, Major N, Boonen S, Haentjens P, Mesenbrink P, Magaziner J, Adachi
J, Lyles KW, Hyldstrup L, Bucci-Rechtweg C, Recknor C. Association between timing of zoledronic acid
infusion and hip fracture healing. Osteoporos Int2010 Dec 9. [PMID: 21153021] (RC 1)
Colon-Emeric CS, Mesenbrink P, Lyles KW, Pieper CF, Boonen S, Delmas P, Eriksen EF, Magaziner J.
Potential mediators of the mortality reduction with zoledronic acid after hip fracture. J Bone Miner Res2010
Jan;25(1):91-7. [PMID: 19580467] (RC 1)
Crawford GB, Khedkar A, Flaws JA, Sorkin JD, Gallicchio L. Depressive symptoms and self-reported fast-food
intake in midlife women. Prev Med 2011 Mar-Apr; 52(3-4):254-7. [PMCID: 3062726] (RC 5)
D’Adamo CR, Shardell MD, Hicks GE, Orwig DL, Hochberg MC, Semba RD, Yu-Yahiro JA, Ferrucci L,
Magaziner JS, Miller RR. Serum vitamin E concentrations among highly-functioning hip fracture patients are
higher than in non-fracture controls. Nutrition Res 2011 Mar;31(3):205-14 [PMID:21481714] (RC 1, RCDC)
Gardner AW, Montgomery PS. Resting energy expenditure in patients with intermittent claudication and
critical limb ischemia. J Vasc Surg 2010 Jun;51(6):1436-41. Epub 2010 Apr 10 [PMCID: 2874602] (RC 3)
Gardner AW, Montgomery PS. Resting energy expenditure in subjects with and without intermittent
claudication. Metabolism. 2009 Jul;58(7):1008-12 [PMCID: 2759316] (RC 3)
Gardner AW, Montgomery PS, Ritti-Dias RM, Forrester LW. The effect of claudication pain on temporal and
spatial gait measures during self-paced ambulation. Vasc Med 2010 Feb;15(1):21-6. Epub 2009 Sep 25
[PMCID: 2810355] (RC 2)
Globas C, Becker C, Cerny J, Lam J, Lindermann U, Forrester LW, Macko RF, Luft AR. Elderly chronic
stroke survivors benefit from aerobic treadmill exercise: A randomized, controlled trial. Annals of Neurology.
(In Review) (RC 1, 3)
Globas C, Lam JM, Zhang W, Imanbayev A, Hertler B, Becker C, Whitall J, McCombe-Waller S, Mori S,
Hanley DF, Luft AR. Mesencephalic corticospinal atrophy predicts baseline deficit but not response to
unilateral or bilateral arm training in chronic stroke. Neurorehabil Neural Repair 2011 Jan;25(1):81-7. [PMID:
20947492] (RC 2)
Ivey FM, Hafer-Macko CE, Ryan AS, Macko RF. Impaired leg vasodilatory function after stroke: adaptations
with treadmill exercise training. Stroke 2010 Dec;41(12):2913-7. [PMID: 20966405 NIHMS: 259879] (RC 1,
2, 3, RCDC, PESC)
Ivey FM, Ryan AS, Hafer-Macko C, Macko RF. Improved cerebral vasomotor reactivity after exercise training
in hemiparetic stroke survivors. Stroke 2011. (In Press) (RC 1, 3, RCDC)
Joseph LJ, Prigeon RL, Blumenthal JB, Ryan AS, Goldberg AP. Weight loss and low intensity aerobic exercise
reduce the prevalence of metabolic syndrome in obese postmenopausal women. J Gerontol (In Press) (RC 3, 5,
RCDC)
Khanna I, Roy A, Rodgers MM, Krebs HI, Macko RF, Forrester LW. Effects of unilateral robotic limb loading
on gait characteristics in subjects with chronic stroke. Journal of NeuroEngin Rehab. J Neuroeng Rehabili 2010
May 21;7:23. [PMCID: 2887457] (RC 2)
McCombe-Waller SM, Prettyman MG. Postural adaptation implicitly occurs during upper extremity training in
standing post stroke. J Neur Physical Therapy. (Submitted March 2011) (RC 2)
Miller RR, Eastlack M, Hicks GE, Alley DE, Shardell MD, Orwig DL, Goodpaster BH, Chomentowski PJ,
Hawkes WG, Hochberg MC, Ferrucci L, Magaziner J. Asymmetry in CT scan measures of thigh muscle 2
months after hip fracture: The Baltimore Hip Studies. J Applied Physiol (Submitted March 2011) (RC 1, 3,
RCDC)
Mizelle JC, Forrester LW, Hallett M, Wheaton LA. Electroencephalographic reactivity to unimodal and
bimodal visual and proprioceptive demands in sensorimotor integration.
Experimental Brain Research. 2010 Jun;203(4):659-70. Epub 2010 May 6. [PMID: 20445965] (RC 2)
Muniyappa R, Veldhuis JD, Harman SM, Sorkin JD, Blackman MR. Effects of testosterone administration on
nocturnal cortisol secretion in healthy older men. J Gerontol A Biol Sci Med Sci2010 Nov;65(11):1185-92.
[PMCID: 2954240] (RC 5)
Nahm ES, Barker B, Resnick B, Covington B, Magaziner J, Brennan PF. Effects of a social cognitive theorybased hip fracture prevention web site for older adults. Comput Inform Nurs2010 Nov-Dec;28(6):371-9.
[PMID: 20978408] (RC 1)
Nahm ES, Resnick B, Orwig D, Magaziner J, Degrezia M. Exploration of informal caregiving following hip
fracture. Geriatr Nurs 2010;31(4):254-262. [PMID: 20682403] (RC 1)
Onwudiwe NC, Stuart B, Zuckerman IH, Sorkin JD. Obesity and medicare expenditure: accounting for agerelated height loss. Obesity (Silver Spring)2011 Jan;19(1):204-11. [PMCID: 3061207] (RC 1, 5, PESC)
Ortmeyer HK, Ryan AS, Hansen BC, Goldberg AP. Low Acyl-CoA synthase activity contributes to skeletal
muscle mitochondrial dysfunction in obese insulin-resistant monkeys. Obesity (In Press) (RC 4)
Orwig D, Hochberg M, Yu-Yahiro J, Resnick B, Hawkes WG, Hebel JR, Colvin P, Miller RR, Golden J,
Zimmerman S, Magaziner J. Delivery and outcomes of a year-long home exercise program after hip fracture.
Arch Intern Med. 2011;171(4):323-331. [PMID: 21357809] (RC 1, 5, RCDC)
Oursler KK, Goulet JL, Crystal S, Justice AC, Crothers K, Butt AA, Rodriguez-Barradas MC, Favors K, Leaf
D, Katzel LI, Sorkin JD. Association of age and comorbidity with physical function in HIV-infected and
uninfected patients: results from the veterans aging cohort study. AIDS Patient Care STDS2011 Jan;25(1):1320. [PMCID: 3030913] (RC 3, 5, RCDC)
Prior SJ, Goldberg AP, Ryan AS. ADRB2 haplotype is associated with glucose tolerance and insulin sensitivity
in obese postmenopausal women. Obesity (Silver Spring) 2011 Feb;19(2):396-401. Epub 2010 Sep 9. [PMCID:
3056391] (RC 3, RCDC, PESC)
Prior SJ, Jenkins NT, Brandauer J, Weiss EP, Hagberg JM. Effects of aerobic exercise training and a high-fat
meal on circulating IGFBP-1 concentration in older adults. (In review) (RC 3, RCDC)
Prior SJ, Ryan AS. Reduced EPC clonogenic potential and skeletal muscle capillarization in impaired glucose
tolerance. (In review) (RC 4, 3, RCDC)
Rich SE, Margolis D, Shardell M, Hawkes WG, Miller RR, Amr S, Baumgarten M. Frequent manual
repositioning and incidence of pressure ulcers among bed-bound elderly hip fracture patients. Wound Repair
Regen2011 Jan;19(1):10-8. [PMCID: 3059225] (RC 1, 5)
Russ DW, Scott WB, Oursler KK, King JS. Paradoxical contractile properties in the knee extensors of HIVinfected men treated with antiretroviral therapy. Appl Physiol Nutr Metab2010 Oct;35(5):713-7. [PMID:
20962928] (RC 3, RCDC)
Ryan AS, Buscemi A, Forrester L, Ivey F, Hafer-Macko C. Atrophy and intra-muscular fat in specific muscles
of the thigh and associated weakness and hyperinsulinemia in stroke survivors (In Revision) (RC 1, 3, 4)
Ryan AS, Ivey FM, Prior S, Li G, Hafer-Macko C. Skeletal muscle hypertrophy and muscle myostatin
reduction after resistive training in stroke survivors. Stroke2011 Feb;42(2):416-20. [PMCID: 3026882] (RC 3,
4, RCDC)
Ryan AS, Ortmeyer HK. Exercise with calorie restriction improves insulin sensitivity and glycogen synthase
activity in obese post-menopausal women with impaired glucose tolerance. Amer J Physiol Endocrinology
(Submitted 2011) (RC 1, 3, 4)
Seliger SL, Betz JF, Steinbrenner G, Waldstein SR, Katzel LI. Physical function and subclinical brain disease
in stage 3-4 CKD. J Am Soc Nephrol 21:658A, 2010 [PMID: 7193126] (RC 3, PESC, RCDC)
Shardell M, Hicks GE, Miller RR, Langenberg P, Magaziner J. Pattern-mixture models for analyzing normal
outcome data with proxy respondents. Stat Med 2010 Jun 30;29(14):1522-38 [PMCID: 3010385] (RC 1, 5)
Shardell M, Hicks GE, Miller RR, Magaziner J. Semiparametric regression models for repeated measures of
mortal cohorts with non-monotone missing outcomes and time-dependent covariates. Stat Med2010 Sep
30;29(22):2282-96. [PMID: 20564729] (RC 1, 5)
Waldstein SR, Lefkowitz DM, Siegel EL, Rosenberger WF, Spencer RJ, Tankard CF, Manukyan Z, Gerber EJ,
Katzel L. Reduced cerebral blood flow in older men with higher levels of blood pressure. J Hypertens2010
May;28(5):993-8. [PMCID: 2878614] (RC 3)
Wendell CR, Hosey MM, Lefkowitz DM, Katzel LI, Siegel EL, Rosenberger WF, Waldstein SR. Depressive
symptoms are associated with subclinical cerebrovascular disease among healthy older women, not men. Am J
Geriatr Psychiatry2010 Oct;18(10):940-7. [PMCID: 2946505] (RC 3)
Whitall J, McCombe-Waller S, Sorkin J, Forrester L, Macko R, Hanley D, Goldberg A, Luft A. Bilateral and
unilateral arm training improve motor function through differing neuroplastic mechanisms: A single-blinded
randomized controlled trial. Neurorehabili Neural Repair 2011 Feb;25(2):118-29. Epub 2010 Oct 7. [PMID:
20930212] (RC 1, 2, 3, 5, RCDC)
UM-OAIC Recognition and Awards
2010-2011

Michael Terrin, M.D., C.M., M.P.H. was recognized with the University of
Maryland Institute for Clinical and Translational Science “Excellence in
Mentoring Award”.
UM-OAIC Minority Research
2010-2011
Ongoing Initiatives
Minority Trainees:
Anindo Roy, Ph.D., Assistant Professor, School of Medicine, Department of Physical
Therapy and Rehabilitation Sciences
Dr. Roy is an Assistant Professor conducting research in rehabilitation robotics including the
development of MIT's newest Ankle Robot with Dr. Forrester in Pepper Center Core 2. Dr.
Roy has an adjunct appointment at the Baltimore Veterans Affairs Medical Center and
collaborates with Claude D. Pepper OAIC studies performing much of the on-site robot tests
with Dr. Forrester and MRI studies with Drs. Hanley and Luft at the Kennedy Krieger MRI
Institute.
Tadas Sean Vasaitis, Ph.D., Postdoctoral Fellow, School of Medicine, Division of
Gerontology and Geriatric Medicine
Dr. Vasaitis is studying effects of exercise and diet on muscle and adipose tissue metabolism,
and factors regulating metabolic responses to resistive exercise, yoga and Vitamin D
repletion on muscle hypertrophy and mitochondrial biogenesis.
Diversity/Minority Supplements:
P.I. Jay Magaziner, Ph.D., M.S.Hyg.
Project Title: The Epidemiology of Bone Strength and Muscle Composition After Hip
Fracture in Men Diversity Award- Grant # 3R01AG029315-01S1
 The primary objective of the diversity supplement is to provide Martha Elizabeth
Eastlack with a series of learning experiences to enhance her capabilities to perform
as an independent investigator. The research and career development experiences
proposed for Dr. Eastlack have four specific aims:
1) Develop further knowledge and skills in muscle molecular biology and
morphology and analytical methods;
2) Build knowledge in gerontology and the population of those with hip
fractures;
3) Obtain experience and credentials as an independent investigator; and
4) Develop a funding application (R-03, R-21, or R01) that builds on newly
acquired knowledge and collaborations.
In the past 2 years Dr. Eastlack has spent 75% of her effort on this project. This has enabled
her to travel several times a month to study and learn techniques used to measure
inflammation in skeletal muscle with Drs. Ryan and Hafer-Macko. Dr. Eastlack has attended
a majority of the UMB monthly meetings of the body composition core for the parent grant
and of the full investigative group to the parent study. Her time has been spent meeting and
working with Dr. Elliott at the University of Pennsylvania to finish work on the MRI
methodology that will be used with the patients after hip fracture to measure muscle crosssectional area and inter- and intramuscular fat in the lower extremity muscles of interest. Dr.
Eastlack received approval for the amended IRB protocol from U Penn during the summer
which incorporates spectroscopy in addition to MRI. In November, Dr. Eastlack attended the
Technical Assistance Workshop (TAW) sponsored by the NIA and attended and presented at
the GSA meeting. As part of the TAW Dr. Eastlack presented and received feedback on her
grant proposal.
UMB Subcontract P.I. Andrew P. Goldberg, M.D.
Project Title: Strength Training to Improve Muscle Function, Quality of Life and
Self Efficacy in Patients with Prostate Cancer, R21 CA127784
 The purpose of this research study is to see if an exercise program to improve muscle
strength is helpful to patients with prostate cancer taking hormone therapy. Hormone
therapy is known to weaken bones and decrease muscle mass but it is unknown if
exercise programs can prevent or reverse this process. The study is being conducted
by the Baltimore VA Medical Center in collaboration with researchers at the
University of Maryland in College Park, Maryland. Up to 75 patients will be
recruited from the Baltimore VA Medical Center and from The University of
Maryland Greenbaum Cancer Center. The testing and training will take place at the
Baltimore VA Medical Center and will require frequent visits to this facility. This
study is being directed by Andrew Goldberg, M.D., at the Baltimore VA Medical
Center in collaboration with Ben Hurley, Ph.D., at the University of MarylandCollege Park. The study offers participation in either the intervention group, which
will receive three months of weight training or a control group that will only
participate in the baseline and post testing portions of the study.
University of Michigan
Claude D. Pepper Older Americans Independence Center
Phone
734-764-3493
FAX
734-936-2116
Electronic
[email protected]
734-936-8198
734-647-9749
[email protected]
Rick A. Bluhm, JD
734-763-3172
734-936-2116
Associate Director for Administration and Program Development
Mailing address:
University of Michigan
Geriatrics Center
300 N. Ingalls St. 9th floor
Ann Arbor, Michigan 48109-2007
[email protected]
Jeffrey B. Halter, M.D.
Center Director
Richard A. Miller, M.D., Ph.D.
Associate Director for Research
SECTION I. CENTER DESCRIPTION
In September 1989, the University of Michigan established the nation's first Claude D. Pepper Geriatrics
Center (UM Pepper Center) funded by the National Institute on Aging. The overall goals of the UM
Pepper Center are to advance research on health care problems of elderly people and to train future
academic leaders in Geriatrics. Drawing on the large base of research currently underway in the fields of
geriatrics and gerontology at the University of Michigan, the UM Pepper Center fosters collaborative
multidisciplinary research to integrate basic science, clinical science, and health services research relevant
to the health care problems of older adults. The UM Pepper Center grant supports important research
activities of the Geriatrics Center at the University of Michigan. Founded in 1987, the Geriatrics Center is
the umbrella organization for geriatrics research, education, and patient care at the University of
Michigan.
The specific goals of the UM Pepper Center are:
1) To support research which has a focus on enhancing the independence of older adults by improved
understanding of predictors and modulators influencing the development of aged phenotypes, including
healthy aging and a range of disablement outcomes.
2) To help maintain and restore the independence of older people by supporting translational research
linking basic with clinical research on aging and common health problems of older adults leading to
disability.
3) To provide Resource Cores (RCs) to support and assist investigator initiated research projects which
can lead to new insights into the basic mechanisms underlying conditions that contribute to aged
phenotypes including comorbidity and loss of independence and which develop and test innovative
methods to apply to such research projects.
4) Through its Research Career Development Core (RCDC), to strengthen the UM environment for
training of future academic leaders who will conduct research on mechanisms contributing to aged
phenotypes, and initiate translational research to enhance independence of older adults.
5) Through its Pilot and Exploratory Studies Core (PESC), to attract UM junior faculty (or selected
senior faculty not previously involved in aging research) to study problems predisposing to aged
phenotypes and to carry out translational research to reduce disablement outcomes.
Faculty from the following Schools and Institutes at the University of Michigan are involved: the Institute
of Gerontology, School of Public Health, Institute for Social Research, Medical School, College of
Engineering, Mental Health Research Institute, School of Nursing, School of Social Work, and College of
Literature, Science, and the Arts. The Geriatrics Center has over 100 affiliated faculty who are principal
investigators on grants totaling $25 million per year in direct costs.
SECTION II. RESEARCH, RESOURCES AND ACTIVITIES
A. CORES
1. BIOMECHANICS CORE
James Ashton-Miller, Ph.D., Core Co-Leader
Neil B. Alexander, M.D., Core Co-Leader
734-763-2320
734-736-3172
[email protected]
[email protected]
The Biomechanics Core provides an array of techniques and equipment for the precise experimental
quantification of physical functioning of healthy and frail elders in order to investigate attributes of the
aging phenotype. It also supplies support for theoretical investigations in the form of computer simulation
models to analyze the elements of those functional abilities and to establish the major determinants of
abilities to perform motor acts in an effective manner.
2. METHODOLOGY, DATA MANAGEMENT AND ANALYSIS CORE
Andrzej T. Galecki, M.D., Ph.D., Core Leader
734-936-2138
[email protected]
The primary goal of MDMAC is to provide methodological, data management, and analytical support to,
and training of OAIC investigators, i.e. junior and senior faculty members at the University of Michigan
(UM) interested in aging research. In particular MDMAC will provide technical support for Pilot
Exploratory Studies (PES), studies conducted by RCDC awardees, and external research projects
conducted by investigators that address the focus of the OAIC – predisposing factors and outcomes of the
aging phenotype – as well as aging research in general. MDMAC faculty will address the following four
aims.
AIM 1: Advice, Planning, and Assistance.
The MDMAC will advise and assist OAIC investigators in methodological design, data management, and
analytical tasks in conducting projects. MDMAC assistance will be available for a number of areas
including data management, biostatistics, survey methodology, and genetics analyses. The Core will
assist in all aspects of conducting the research study, including formulating specific aims and hypotheses,
developing the study design, writing appropriate parts of a proposal, performing sampling and/or
randomization, designing data collection instruments and methods, coding and managing data, providing
statistical modeling, and analyzing quantitative and qualitative data for reporting, interpreting and
presenting results.
AIM 2: Training.
The MDMAC will provide training for OAIC investigators. By maintaining direct contact with OAIC
researchers conducting studies on the elderly, MDMAC is ideally suited to carry out training for new
investigators. A key aspect of MDMAC assistance is instruction and training, via consultations, progress
meetings, and seminars, in the appropriate use of study design, analytic methods, and data management,
especially as applied to studying the elderly. With its emphasis on junior OAIC researchers, the Core
provides a foundation for future effective and efficient use of experts in the development of well-designed
and well-executed studies.
AIM 3: Facilitate Access to Secondary (Archived) Data, Maintain Selected Databases.
The MDMAC will facilitate the access of OAIC Investigators to (large) archived survey and
administrative secondary data sets describing elderly persons. Increasingly, useful secondary data sets are
available for public use. The UM is a leader in this field with the public holdings of the Inter-university
Consortium for Political and Social Research (ICPSR), the Health and Retirement Survey, and
particularly relevant, the National Archive of Computerized Data on Aging (NACDA) which represents
the largest single source of secondary data on aging and health in the United States. The MDMAC also
maintains the Michigan Long-Term Care Master Data Archive (MMDA), archiving nursing home and
home care data and developed in the prior funding period by the OAIC. The MDMAC will help locate,
access, and document for use data sets identified by OAIC Investigators as particularly relevant to their
research.
AIM 4: Methodology Development and Implementation.
The MDMAC will undertake a limited number of internal efforts/projects to identify in existing literature
or develop new methodological approaches, and implement them as software tools. Each year, the
MDMAC will be proactive in selecting areas for methodology development and implementing alreadyavailable methodology into accessible software tools. The methodologies developed can have direct
applicability to studies at UM’s and others’ OAICs, and for gerontological researchers elsewhere.
3. CORE FACILITY FOR AGED RODENTS
Richard Miller, M.D., Ph.D., Core Leader
734-936-2122
[email protected]
The Core Facility for Aged Rodents, CFAR, has been a major feature of the University of Michigan
Claude Pepper Center since its inception in 1989. CFAR serves the needs of Pepper Center investigators
through four Specific Aims.
AIM 1:
To provide advice to OAIC investigators on the choice of animal models for their research
programs, on design of experiments that use rodent animals, and incorporation of gene mapping strategies
into their experimental programs, and to contribute to pilot projects selected by the Pilot/Experimental
Studies Core.
AIM 2:
To support specialized colonies of mice particularly well suited for research on the biology of
aging and its relationship to late-life disease. These include (a) genetically heterogeneous mice of the
UM-HET3 and UM-HET4 stocks; (b) calorically restricted and methionine-restricted UM-HET3 mice;
and (c) mice of the long-lived Idaho, Snell dwarf (dw/dw), GHR-KO, MIF-KO, and PAPPA-KO stocks.
Mice from these colonies will be provided to faculty members working on PESC and RCDC research
projects, as well as to Geriatrics Center faculty members who wish to conduct pilot studies on mouse
aging supported by other sources of NIA funds, or who are working on aging-related problems supported
by other sources.
AIM 3:
To develop new animal models to meet specific experimental goals proposed by Geriatrics
Center faculty. In the first year, funds will be devoted to further characterization of the GHR-KO and
PAPPA-KO mice, production of mice carrying Huntington's Disease susceptibility alleles on the slowaging Snell dwarf background, mice in which mutant alleles of the CDKN2a locus (p16INK4a/Arf) have
been targeted to neural cells, and mice in which Insulin Receptor Substrate-2 (IRS-2) function has been
deleted from brain neurons expressing leptin receptor.
AIM 4:
To develop, test, and employ new methods for analysis of genetic controls on late-life traits in
mice, both by exploiting the rich database of genotypic and phenotypic data already in hand for the UM-
HET3, UM-HET4, and (Idaho x B6)F2 systems, and by acquiring new genotype data on these and related
genetically heterogeneous mice.
4. HUMAN SUBJECTS AND ASSESSMENT CORE
Jersey Liang, Ph.D., Core Co-Leader
Linda Nyquist, Ph.D., Core Co-Leader
734-936-2141
[email protected]
734-936-6078 [email protected]
The major objective of the Human Subjects and Assessment Core (HSAC) is to contribute to improved
understanding of predictors and modulators of aged phenotypes, the focus of the University of Michigan
Older American Independence Center (OAIC) program. In particular, the HSAC has four specific aims:
AIM 1:
To maintain and facilitate access to human subjects and related data sets for projects
consistent with the overall goals of the OAIC.
AIM 2:
To provide periodic assessments of self-reported health conditions, functional status, and
social and psychological measures for subject selection, enrollment, retention, and compliance.
AIM 3:
To expand and promote research on racial, ethnic, and cultural differences in aged
phenotypes through linkages with the Wayne State University Institute of Gerontology (WSU IoG)
minority participant registry and University of Michigan CTSA (MICHR) Health Disparities Research
Program.
AIM 4:
To provide training and consultation to OAIC researchers on issues related to (a) recruitment
and retention of human subjects, (b) measurement of quality of life and other behavioral and lifestyle
variables in research on aging and health, and (c) longitudinal analysis of health in old age.
5. RESEARCH CAREER DEVELOPMENT CORE (RCDC)
Neil B. Alexander, M.D., Core Leader
734-736-3172
[email protected]
The primary goal of the Research Career Development Core (RCDC) is to recruit, select, support, mentor,
and train junior faculty to become independent investigators in aging-related research and academic
leaders in geriatrics and gerontology within their respective disciplines. The RCDC focuses on
stimulating the translation between basic and clinical research across the spectrum of its training activities
including the annual research career development retreat. To this end it serves a critical function in
supporting the overall OAIC focus by training the next generation of investigators whose research will
lead to an improved understanding of the predictors and modulators of the aging phenotype.
6. PILOT and EXPLORATORY STUDIES CORE (PESC)
Raymond Yung, M.D., Core Co-Leader
Caroline Blaum, M.D., Core Co-Leader
734-647-9746
734-936-4493
[email protected]
[email protected]
The goal of the Pilot and Exploratory Studies Core (PESC) is to provide support for studies that will
develop and test new research ideas of high relevance to the Center's overall theme, the predictors and
modulators of the aging phenotype and the ways in which genetic, environmental, and social factors
influence late life disease through effects on the aging process. The PESC thus funds pilot research
studies over a wide range of disciplines, ranging from basic genetics and physiology through behavioral
and health services research.
7. LEADERSHIP/ADMINISTRATIVE CORE
Jeffrey Halter, M.D., Center Director
734-764-3493
[email protected]
To provide cohesion and coordination among the UM Pepper Center cores and their multiple programs,
the Leadership /Administrative Core forms the apex of the UM Pepper Center framework of programs.
This central core promotes development of the Center's goals by fostering interactions among the Center
Director, the coordinators for each program area, key research and training faculty within the University,
and the leadership structure of the institution. The Administrative structure and the advisory committees
of the UM Pepper Center define, enhance, and require these interactions on a regular and ongoing basis.
This coordinating task of the Leadership /Administrative Core is of paramount importance to ensure that
the activities of the UM Pepper Center continue to focus on meeting the specific goals outlined upon its
inception.
B. PILOT- PROJECTS -YEAR 01 TO PRESENT
5 Year Cycle 1989-1990
Year 01
Biomechanics of Rising from a Chair in the Elderly
Neil Alexander, M.D., Assistant Professor of Internal Medicine (Geriatrics)
Gene Expression in Aging Muscle
Kate Barald, Ph.D., Associate Professor of Anatomy
The Role of Interleukin-6 in Aging
Suzanne Bradley, M.D., Assistant Professor of Internal Medicine (Geriatrics)
Effect of Aging on Repair of the Kidney following Ischemic Injury
David H. Humes, M.D., Professor of Internal Medicine (Nephrology)
Studies on Receptor-mediated Polyphosphoinositide Turnover and Intracellular Calcium
Metabolism in Fibroblasts from Alzheimer's Patients and Healthy Controls
Alan Mellow, M.D., Ph.D., Assistant Professor of Psychiatry
Wisdom in Later Adulthood: Psychological Correlates
Lucinda Orwoll, Ph.D., Research Fellow, Institute of Gerontology
Protease Nexin 1: A Model for Trophic Factor Production in Normal and Pathologic Aging
Dorrie Rosenblatt, M.D., Ph.D., Assistant Professor of Internal Medicine (Geriatrics)
Sympathetic Function in Elderly Human Hypertensives
Mark Supiano, M.D., Assistant Professor of Internal Medicine (Geriatrics)
Pilot for a Survey of Arthritis and Disability in Daily Life
Lois Verbrugge, Ph.D., Research Scientist, Institute of Gerontology
Year 02 1990-1991
HSV-Mediated Gene Transfer Studies of Amyloid and NGF
David Fink, M.D., Associate Professor of Neurology
Effect of Aging on Acute Phase Response
Matthew Kluger, Ph.D., Professor of Physiology
Hospital Admissions from VA Nursing Homes
David Mehr, M.D., Instructor of Family Practice
Gene Regulation in Senescent Cells
Bruce Troen, M.D., Assistant Professor of Internal Medicine (Geriatrics)
Functional Properties of Nerve-Repaired Vascular Intact Grafts in Young, Adult, and Old Rats
Edwin Wilkins, M.D., Instructor of Surgery
Year 03 1991-1992
The Cross-Age Effect in Transplanted Nerve Segments
Bruce Carlson, M.D., Ph.D., Professor of Anatomy and Cell Biology
Genetic Investigation of Alzheimer and Creutzfeldt-jakob Diseases
John Fink, M.D., Assistant Professor of Neurology
The Effects of Aging on Vascular Gene Expression
Rory Marks, M.D., Assistant Professor of Internal Medicine (Rheumatology)
Role of Charge-Transfer Interactions in Age-Related Protein Modifications
Joseph Schauerte, Ph.D., Research Investigator, Biological Chemistry
Effect of Aging on Calcium Channel Function in Gastrointestinal Neuromuscular Preparations
John Wiley, M.D., Assistant Professor of Internal Medicine (Gastroenterology)
Year 04 1992-1993
Gene Expression in the Aging Hepatocyte
Bahri M. Bilir, M.D., Lecturer, Internal Medicine (Gastroenterology)
Characterization of Protein Tyrosine Phosphates in Yeast Activation of the Kinase Cascade in
Mitogenic Growth Factor Signal Transduction
Kunliang Guan, Ph.D., Assistant Professor and Assistant Research Scientist, Biological Chemistry and
Assistant Research Scientist, Institute of Gerontology
Aging and Immunologic Homeostasis: Regulation of Osteopontin Production in T-Lymphocytes
Laurie K. McCauley DDS, Assistant Professor of Periodontics/Prevention/Geriatrics, School of Dentistry
Myosin Phenotype and Altered Contractile Function in Heart During Aging
Joseph M. Metzger, Ph.D., Assistant Professor of Physiology
Trends in Self-Reported Health and the Prevalence of Chronic Conditions
Timothy A. Waidmann, Assistant Professor of Public Health Policy and Administration, School of Public
Health
Assessing the Quality of Medical Care in Nursing Homes Using Routinely Collected Information
Brent C. Williams, M.D., Instructor of Internal Medicine (Geriatrics)
Year 05 1993-1994
The Impact of Chronic Diseases on Health Outcomes
Caroline Blaum, M.D., Lecturer, Internal Medicine (Geriatrics)
Stability of Gene Repression During Mammalian Aging
David Burke, M.D., Assistant Professor of Human Genetics
Characterization of Protein Tyrosine Phosphates in Yeast Activation of the Kinase Cascade in
Mytogen Mitogenic Growth Factor Signal
Kunliang Guan, Ph.D., Assistant Professor and Assistant Research Scientist, Biological Chemistry and
Assistant Research Scientist, Institute of Gerontology
Transcriptional Regulation in T cells from Mice of Different Ages
David Markovitz, M.D., Assistant Professor of Internal Medicine (Infectious Diseases)
Expression of the Extracellular Matrix Protein Thrombospondin in the Aging
Sue K. O'Shea, Ph.D., Assistant Professor, Anatomy and Cell Biology
Age-Dependent Changes in Adhesion Molecule Expression and Function on T Lymphocytes
Yoji Shimizu, Ph.D., Assistant Professor, Microbiology and Immunology
5 year Cycle 1994-1995
Year 06
Effects of Nerve Growth Factor on Age-Associated Changes of Neuronal Calcium Signaling
Karen Hall, M.D., Ph.D., Research Investigator, Internal Medicine (Gastroenterology)
T Cell Mediated Host Defenses in the Lungs of Aged Mice
Gary B. Huffnagle, Ph.D., Research Investigator, Internal Medicine (Pulmonary)
Telomere Sequence Variations as a Possible Mechanism of Programmed Cellular Senescence
Vladimir L. Makarov, Ph.D., Assistant Research Scientist, Biophysics Research Division
Breathlessness During Maximal Exercise in Elderly Humans
Fernando Martinez, M.D., Assistant Professor of Internal Medicine (Pulmonary)
Neurobehavioral Studies of Age-Related Changes in Working Memory
Patricia A. Reuter-Lorenz, Assistant Professor of Psychology
Year 07 1995-1996
The use of Mupirocin as a Model for the Prevention of Staphylococcal Infection and Emergence of
Antibiotic Resistance in Elderly Patients
Suzanne F. Bradley, M.D., Assistant Professor of Internal Medicine (Geriatrics)
New Diagnostic Measures of Balance Performance in Elderly
Arthur D. Kuo, Ph.D., Assistant Professor of Mechanical Engineering and Applied Mechanics, Assistant
Professor of Biomechanical Engineering, College of Engineering, Institute of Gerontology
Regulation of IL-4 Production and its Role in Aging
Cheong-Hee Chang, Ph.D., Assistant Professor of Microbiology and Immunology
Year 08 1996-1997
The Contribution of Antagonistic Interactions Among T Cell Subsets
Igor Dozmorov, Ph.D., Assistant Research Scientist (Pathology)
Nursing Home to Nursing Home Transfers: The Neglected Transition
Richard A. Hirth, Ph.D., Assistant Professor of Health Management (SPH)
Vasomotor Insulin Resistance in NIDDM: Endothelial Mechanisms
Robert Hogikyan, M.D., Assistant Professor of Internal Medicine (Geriatrics)
The Effect of Aging on Cell Mediated Immunity in the Lungs
Gary B. Huffnagle, Ph.D., Assistant Research Scientist of Internal Medicine (Pulmonary)
Relationship of Age to the Osteogenic Potential of Marrow Stroma
Paul H. Krebsbach, Ph.D., Assistant Professor of Dentistry
NOS MRNA Expression of the Gastric Myenteric Plexus
Toku Takahashi. M.D., Ph.D., Assistant Research Scientist of Internal Medicine (Gastroenterology)
Year 09 1997-1998
Health Care Outcomes and Utilization in Older Patients with Coexisting Dementia and Depression
Helen Kales, M.D., Lecturer in Psychiatry
The Effect of Acetyl-L-Carnitine on the Quality and Function of Senescent Skeletal Muscle
Lisa Larkin Ph.D., Assistant Research Scientist, Internal Medicine (Geriatrics)
Corticosteroid Receptors and the Aging Hippocampus
Maria Morano, Ph.D., Research Investigator, Mental Health Research Institute
Lymphocyte Homing in Age
Raymond Yung, M.D., Assistant Professor of Internal Medicine (Geriatrics)
Year 10 1998-1999
Genetic Mapping of Qualitative Trait Loci Using Four-Way Crosses
Andrjez Galecki, Assistant Research Scientist, Institute of Gerontology
Recipient Age as a Determinant of GVHD
James Ferrara, M.D., Director, Combined BMT Program
5 Year Cycle
Year 11 1999-2000
Effects of Age and Exercise Training on Skeletal Muscle Protein Turnover
Donald Dengel, Ph.D., Assistant Research Scientist of Internal Medicine (Geriatrics)
Prospective Evaluation of Losartan in Preventing Age-Dependent Endothelial Dysfunction
(PREVAILED)
Sanjay Rajagopalan, M.D., Assistant Professor of Internal Medicine (Cardiology)
Leukotriene Overproduction and Aging
Thomas Brock, Ph.D., Assistant Research Scientist of Internal Medicine (Pulmonary)
Year 12 2000-2001
Age Associated Alterations in T Cell Activation Revealed by Gene Expression Analysis
Igor Dozmorov, Ph.D., Assistant Research Scientist (Pathology)
Effect of Aldosterone Receptor Blockade on Cariovascular Aging
Marvin Boluyt, Ph.D., Assistant Professor (Kinesiology)
Inter-relationships Between Diabetes and Periodontal Disease in Aging Veterans
George W. Taylor, DM.D., DrPh, Associate Professor, School of Dentistry
Year 13 2001-2002
Hospice Utilization and End-of-Life Costs Among End-Stage Renal Disease Patients
Richard Hirth, Ph.D., Associate Professor, Health Management & Policy, School of Public Health
Skeletal Muscle Gene Expression Profile in Aging and Exercise
Lisa Larkin, Ph.D., Assistant Research Scientist (Geriatrics)
Home Training of Elderly CHF Patients
Peter Vaitkevicius, M.D., Assistant Professor (Geriatrics)
Relationship of Stem Cell Numbers to Aging of the Immune System in UM HET-3 Mice
Michael Clarke, M.D., Professor of Internal Medicine (Hematology/Oncology)
Year 14 2002-2003
Functional stratification of older adults with diabetes
Caroline Blaum, M.D., Assistant Professor, Internal Medicine (Geriatrics)
Cognitive demands while walking in older individuals with and without cognitive impairment
Carol Persad, Ph.D., Clinical Assistant Professor, Division of Neuropsychology
Year 15 2003-2004
Age-related declines in bimanual coordination: neural mechanisms and potential for compensation
Rachael Seidler, Ph.D., Assistant Professor, Division of Kinesiology and Department of Psychology
Oxidative stress in age-related hearing loss
Suhua Sha, M.D., Research Investigator, Kresge Hearing Research Center
Alcohol trajectories of older persons in Japan
Gilbert Gee, Ph.D., Assistant Professor, Department of Health Behavior and Health Education, School of
Public Health
A tailored physical activity program for patients with congestive heart failure
Kimberler Gretebeck, Ph.D., Assistant Professor, School of Nursing
New 5 yr Cycle
Year 16-2004-2005
Insulin responses of muscle cells in vitro
Gregory D. Cartee, Ph.D., Professor of Kinesiology
Patterns and Prpedictors of alcohol use trajectories among aging Americans
Gilbert C. Gee , Ph.D., Assistant Professor of Health Behavior and Health Education, School of Public
Health
Mechanical consequences of genetically-influenced bone composition
McCreadie, Barbara, Ph.D., Research Investigator, Orthopaedic Research Labs
Factors moderating falls risk while turning among frail and healthy old adults
Carol Persad, Ph.D., Clinical Assistant Professor, Division of Neuropsychology
Year 17-2005-2006
Anal sphincter structure-function relationships in aging and fecal incontinence
Dee Fenner, Associate Professor of Obstetrics and Gynecology
Role of mineralocorticoid receptor in age-related deficits in hippocampal function
Audrey Seasholtz, Research Professor of Biological Chemistry
Influence of PKC isoform expression on myocyte contractile function during aging
Margaret Westfall, Assistant Professor of Surgery
Using electronic pharmacy fill and refill data to understand and promote appropriate medications
use among elderly patients with hypertension
Michele Heisler, Assistant Professor of Internal Medicine
Perceptions of oral health adequacy and access in long-term care
Barbara Smith, Assistant Professor of Periodontics
Year 18-2006-2007
Age-dependent dendritic cell function: implication for cancer vaccine therapy
Annabelle Grolleau, Ph.D., Research Investigator, Division of Geriatric Medicine
Modulation of stress resistance and aging in mice
James Harper , Ph.D., Research Invesitgator, Pathology
Non-fatal suicidal behavior in home care elderly: The role of physical symptoms, functional
disability, and cognitive impairment
Lydia Li, Ph.D., Associate Professor of Social Work, School of Social Work
Enhancing caregiver support for chronically ill older adults
John Piette, M.D., Associate Professor of Internal Medicine
Role of fatty acid transport in aging Drosophila heart
R.J. Wessells, Ph.D., Clinical Lecturer, Division of Geriatric Medicine
Lymphocyte apoptosis in elderly emergency patients
John Younger, M.D., Associate Professor of Emergency Medicine
Year 19-2007-2008
A tailored clinical intervention for older adults with leg OA
Susan Murphy, M.D., Assistant Professor, Physical Medicine and Rehabilitation
Use of a single underfoot perturbation to assess how age, peripheral neuropathy, and divided
attention affect gait stability
Joseph Nnodim, M.D., Assistant Professor, Division of Geriatric Medicine
Molecular mechanisms of oxidative stress in frailty and diabetes
Subramaniam Pennathur, M.D., Assistant Professor of Nephrology
REM sleep modulation as a target for age-related learning and memory deficits
Gina Poe, M.D., Associate Professor of Anesthesiology
The effect of vibrotactile tilt feedback on postural and gait stability in older adults
Kathleen Sienko, Ph.D., Assistant Professor of Mechanical Engineering, College of Engineering
Year 20-2008-2009
Do depressive symptoms lead to disability and vice versa?
Xiao Xu, Ph.D., Research Investigator, Department of Obstetrics and Gynecology, Medical School
Utility of aerobic rat models for the study of frailty
Lauren Koch, Ph.D., Assistant Professor, Department of Physical Medicine and Rehabilitation, Medical
School.
The relationships between brain white matter abnormalities, cognition and the biomechanics of
(dual task) balance and gain in older adults
Martijn Mueller, Ph.D., Research Investigator, Department of Radiology Medical School
Molecular epidemiology of methicillin-resistant Saphylococci in nursing homes
Lona Mody, M.B.B.S., Assistant Professor, Department of Internal Medicine, Medical School.
Falls and urinary incontinence in the older adult population
Christine Cigolle, M.D. Clinical Lecturer, Department of Family Medicine, Medical School
The prevalence of cognitive decline in older adults with chronic heart failure
Tanya Gure, M.D., Clinical Lecturer, Department of Internal Medicine, Medical School
The effect of dietary fatty acids on the sarcopenia of aging
Angela Subauste, M.D., Lecturer, Department of Internal Medicine /MEND
The role of cognitive and affective variables in explaining increased risk of falls
Sara Wright, Ph.D. Clinical Lecturer, U-M Department of Psychiatry, Medical School
Randomized, placebo controlled study to evaluate the safety and efficacy of efalizumab
Bruce Richardson, M.D., Ph.D., Professor, Rheumatology, Department of Internal Medicine, Medical
School
Functioning after severe sepsis
Theodore Iwashyna, M.D., Ph.D., Assistant Professor of Internal Medicine, Pulmonary & Critical Care,
Medical School
Year 21-2009-2010
Elucidation of the role of mitochondrial protein acetylation in calorie restriction in mammals
David B. Lombard, M.D., Ph.D., Assistant Professor of Pathology, Medical School
A Theory-Informed Intervention to Reduce Hip Fracture
Lustig, Cindy A., Ph.D., Assistant Professor, Psychology
The Effect of COMT Genotype on Age-Related Declines in Motor Function
Rachael Seidler, Ph.D., Associate Professor, Psychology and School of Kinesiology.
Estimating Health Trajectories In Old Age: How Much Does Selection Bias Matter?
Wen Ye, Ph.D., Assistant Professor in the Department of Biostatistics, School of Public Health
Year 22- 2010-2011
Protection of Auditory Function in Late Life by Heat Shock Factor 1
David Kohrman, Ph.D., Associate Professor Department of Human Genetics, Department of
Otolaryngology/Head and Neck Surgery
Racial Differences in Cognitive Decline: The Influence of Stroke
Deb Levine, M.D., M.P.H., Assistant Professor of Internal Medicine and Neurology
Nitric Oxide In Aging and Longevity
Nancy Linford, Ph.D., Research Investigator of Molecular and Integrative Physiology
Improvement of Immune Function in CD4 cell from old mice.
Gonzalo Garcia, Ph.D., Research Investigator of Pathology
P2X7 Receptors in the Retinal Pigment Epithelium: Effect of Aging.
Dongli Yang, M.D., Ph.D., Research Investigator of Ophthalmology and Visual Sciences
Hospitalists and the care of Older Adults
Lena Chen, M.D., M.S., Clinical Lecturer of Internal Medicine
Diabetes Management in the Oldest Old Adults
Pearl Lee, M.D., Assistant Professor, Geriatrics
SECTION III. Career Development (Listing From 1999-2009 of Funding Subsequent To Pepper
Center Pilot Funding). Current academic titles are provided. All at University of Michigan, unless
noted otherwise.
Andrzej T. Galecki, Research Professor, Institute of Gerontology (1999)
Grants Awarded:
NIH, "Genetics of Age-Sensitive Traits in Mice,” R. A. Miller, PI. Period of award: 5/99-4/04.
NIH/NIA, "Genetic Control of Longevity in Mice," R. A. Miller, PI. Period of award: 4/99-11/04.
NIH-Michigan State University “Family Home Care for Cancer: A Community-Based Model, Galecki,
Andrzej, T PI Period of award 04/01/2003 to 03/31/2006.
NIH, “Laboratory for Anti-Geric Testing” R.A. Miller, PI. Period of award: 7/03-6/14
NIH/NIA, “Molecular Regulation of CC Chemokine Receptors in Atherosclerosis and Aging.” R. Yung,
PI. Period of award: 9/06-6/11
NIH/NIA, “Training in Older Adult Mobility Research.” N. Alexander, PI. Period of award: 9/07-9/12
NIH/NIA, “Claude D. Pepper Older Americans Independence Center.” J. Halter, PI. Period of award:
9/09-8/14
NIH/NIA, “Targeted Infection-control Program (TIP) to Reduce Resistant Pathogens and Infections in
Nursing Homes.” L. Mody, PI. Period of award: 9/09-8/14
NIH, “Enterics Research Investigators Network, Project 3: Clostridium difficile Cooperative research
Center (U19): Arnoff (PI).” V. Yung (PI). Period of Award: 7/10-6/15.
Honors, awards, promotions:
Promoted from Research Assistant Professor to Research Associate Professor in 2000 and Research
Professor in 2008.
Thomas G. Brock, Editor, InScience (1999)
Grants Awarded:
NIH- “5-Lipoxygenase Structure and Function in Mucosal Epithelium” Brock, Thomas-PI
Period of Award 09/01/2000 to 08/31/2003.
NIH- Regulation of Nuclear Import/Export of 5-Lipoxygenase,Brock, Thomas-PI
Period of Award 09/01/2000 to 08/31/2003.
NIH- “Regulation of Nuclear Import/Export of 5-Lipoxygenase”, T. Brock, PI. Period of award
08/01/2002 to 07/31/2007
Honors, awards, promotions:
Promotion from Assistant Research Scientist
James Ferrara, Professor, Internal Medicine and Pediatrics (1999)
Grants Awarded:
NIH-“ A Phase I/II Trial of Recombinant Human Keratinocyte Growth Factor (rHuKGF) to Prevent
Acute Graft-Versus-Host Disease (GVHD) in 6/6 HLA=Bone Marrow Transplant (BMT) Recipients IND
8783” Ferrara, James-PI Period of Grant 09/01/2001 to 08/31/2003
NIH- University of Michigan Core Clinical Center of the Bone Marrow Transplant (BMT) Research
Network, Ferrara, James-PI Period of Award 09/30/2001 to 08/31/2006
NIH-“Cellular and Molecular Studies of Bone Marrow Transplant” Ferrara, James-PI
Period of Award 05/01/2001 to 04/30/2004
Doris Duke Charitable Foundation-“Novel Strategies to Improve Allogeneic Bone Marrow Transplant
(BMT)” Ferrara, James-PI
Period of Award 12/15/2002 to 12/14/2007
Honors, awards, promotions:
Doris Duke Distinguished Clinical Scientist Award
George W. Taylor, Professor, Cariology, Dental School, retired from University effective 9/1/11
(2000)
Grants Awarded:
NIH “Diabetes Associations with Caries and Tooth Loss in NHanes III: Taylor, George PI
Period of Award 07/01/2004 to 04/30/2006
NIH “Oral Infections: Impact on Gestational Diabetes: Taylor, George, PI
Period of Award 10/01/2004 to 07/31/2006
NIH “Periodontal Therapy: Effects on Glycemic Control in Community Health Centers: Taylor, George,
PI . Period of Award 03/01/2006 to 02/29/2008
Blue Cross Blue Shield of Michigan Foundation – “Is Periodontal Treatment Associated with Lower
Medical Costs in Adults with Diabetes?” G. Taylor, PI.
Period of award 10/01/2006 to 09/30/2007
NIH “Two-Way Interrelationships: Periodontal Disease, Diabetes and Its Complications: Taylor-PI
Period of Award 03/01/2008 to 02/28/2010
Honors, awards, promotions:
National Dental Association Foundation/Colgate Palmolive Faculty Recognition Award for Research in
2002
Promoted to Associate Professor with tenure in September, 2000.
Promoted to Professor, September, 2009.
Lona Mody, Associate Professor, Internal Medicine (Geriatric Medicine) (2000)
Grants Awarded:
NIH K 23 Mentored Patient-Oriented Research Career Award. “Device use in Nursing Homes: Reducing
the Risk of Infection,” Lona Mody, PI. Period of award: 7/03-6/08.
NIH “Device Use in Nursing Homes: Reducing Risk of Infection” Mody, Lona PI
Period of Award 09/30/2003 to 08/31/2008.
AGS Foundation for Health in Aging “Antimicrobial Resistance in Nursing Homes: Implications for
Indwelling Device Use” Mody, Lona, PI, Period of Award 07/01/2005 to 08/31/2007
John A. Hartford Foundation, Center of Excellence in Geriatrics.
NIH R01 Targeted Infection-control Program (TIP) to Reduce Resistant Pathogens and Infections in NHs,
Lona Mody, PI. 9/15/2009 to 8/31/2014
Cepheid, Clinical Evaluation of the Xpert MRSA/SA Assay In Nasal Swabs, Lona Mody PI. 5/1/2009 to
5/1/2011
Dennis Claflin, Research Assistant Professor, Section of Plastic & Reconstructive Surgery, Dept. of
Surgery (2000)
Grants Awarded:
NIH- “Animal Models of Limb Girdle Muscular Dystrophy 1A” Claflin, D. Co-Investigator
Period of Award 04/01/2001 to 03/31/2004
NIH-“ Cellular and Molecular Biology of Aging” Claflin, D. Co-Investigator.
Period of Award 07/01/2005 to 06/30/2010
NIH “Chemical-Based Membrane Sealants for Dystrophic Muscle” Claflin, Co Investigator
Period of Award 09/01/2007 to 06/30/2011
Cytokinetics “Acute Administration of CK1909178 and CK2017357 in an In-Vitro Permeabilized Muscle
Fiber Analysis System Using Human Tissue” Claflin-PI
Period of Award 07/24/2007 to 07/23/2008
Richard A. Hirth, Professor, Health Mgmt and Policy, School of Public Health (2001)
Grants Awarded:
NIH “Health Services Research Training” Hirth, RA-PI, Period of Award 07/01/2003 to 06/30/2008.
NIH “Implementation Support for the Quality Incentive Payment of the ESRD Disease Management
Demonstration” Hirth, RA-PI, Period of Award 10/01/2004 to 09/29/2006.
HHS DCMM-“End-Stage Renal Disease Prospective Payment System (ESRD PPS). R. Hirth, PI.
Period of award 09/25/2006 to 09/24/2011.
HHS HCRQ “Payment Systems, Market Factors and Long-Term Care Hospitals” Hirth-PI. Period of
Award 08/01/2007 to 07/31/2008
Peter Vaitkevicius, Associate Professor, Wayne State University School of Medicine, Cardiology
Fellowship Director, Oakwood Medical Center/Wayne State University (2001)
Grants Awarded:
Veterans Administration Merit Review Grant VA Ann Arbor Healthcare System, University of Michigan,
“Functional Circuit Training in Older Adults with Congestive Heart Failure,” N. Alexander, PI; P.
Vaitkevicius, Co-Investigator. Period of award: 01/04-1/09.
Blue Cross and Blue Shield of Michigan Health Foundation, Palliative Care Consultation for Hospitalized
Patients with Severe Heart Failure: A Randomized Trial. Vaitkevicius, Co-Principal 1/2006-1/2008.
Blue Cross and Blue Shield of Michigan Health Foundation, Preclinical Cardiac Dysfunction Among
Asymptomatic Hypertensive Patients Presenting to an Urban Emergency Department: A Prevalence
Study. Vaitkevicius Co-Investigator 2/2006-2/2007.
VA Ann Arbor Healthcare System, Merit Review, Evaluation of Cardiac Nurse Practitioner Palliative
Care Program. Vaitkevicius, PI 1/2005-6/2009.
Pfizer Inc. A Randomized. Double Blind, Multi-center, Study Evaluation the Effects of Eplerenone
versus Placebo on Ventricular Remodeling in Patients with Left Ventricular Systolic Dysfunction
(EF<35%) and Mild to Moderate Heart Failure. P. Vaitkevicius, PI 8/2004-2005.
Honors, awards, promotions:
Chief of Cardiology, John D. Dingle VA Medical Center, Detroit, Michigan (2005-)
Interim Chief, Division of Cardiology, Wayne State Univ. School of Med, (2005-2007 )
Cardiology Fellowship Director, Oakwood Medical Center/Wayne State University (2007-)
Associate, Internal Medicine/Cardiovascular Disease, Barbara Ann Karmanos Cancer Institute (2005-)
John Wei, Professor, Urology (2001)
Grants Awarded:
Health and Human Services, Department of-National Institutes of Health-Subcontracts, “Survivor
Quality-of-Life (QoL) and Spouse Satisfaction After Prostate Therapy”. J. Wei, PI. Period of award:
01/01/2004 to 06/30/2004.
Glaxo Wellcome, PLC, “Progression of Benign Prostatic Hyperplasia Among a Cohort of AfricanAmericans: Flint Men's Health Study”. J. Wei, PI. Period of award: 07/01/2003 to 03/31/2004.
NIH “Survivor Quality-of-Life (QoL) and Spouse Satisfaction After Prostate Therapy”
Wei, JT-PI Period of Award 01/01/2004 to 06/30/2006
NIH-Harvard “Harvard-Michigan Prostate Cancer Biomarker Clinical Validation Center” Wei, JTPIPeriod of Award 03/29/2005 to 02/28/2007
Envisioneering Medical Technologies “A Phase II Evaluation of TargetScan Guided Prostate Needle
Biopsy” Wei-PI. Period of Award 07/01/2006 to 06/30/2007
American Urological Association Foundation “Assessing Patient-Centered Survivorship Care in Prostate
Cancer” Wei-PI Period of Award 07/01/2007 to 06/30/2008
Honors, awards, promotions:
Promoted to Associate Professor in 2004
Professor, Department of Urology
Tzy-Wen Gong, Research Investigator, Kresge Hearing Research Institute (2002)
Grants Awarded:
Deafness Research Foundation “Role of Ubiquitin Ligase UBE3B in Response to Noise Trauma in the
Chick Inner Ear” Gong, TL-PI. Period of Award 07/01/2004 to 06/30/2006
Center for Occupational Health and Safety Engineering NIH “Stress Pathways in Age-Related Hearing
Loss” Gong, TL-PI, The role of inflammatory response in noise-induced hearing loss Period of Award
07/01/2005 to 07/31/2010
Sharon L.R. Kardia, Professor and Chair of Epidemiology, School of Public Health (2002)
Grants Awarded:
AG12975, “Epidemiology of Functional Status in Elderly Hispanics,” M. Haan, PI, S. L. R. Kardia, CoInvestigator. Period of award: 9/03-6/08.
NIH “Predictors of Blood Pressure in Hypertensives” Kardia SR-PI, Period of Award 10/01/2003 to
09/30/2006
NIH “Genetic and Molecular Signaling in Heart Failure” Kardia, SR-PI. Period of Award 02/22/2005 to
12/31/2006
NIH “The Family Blood Pressure Program (GENOA Network)” Kardia, SR-PI. Period of Award
09/30/2005 to 08/31/2006
NIH “Education for Community Genomic Awareness”. Kardia SR-PI. Period of award 4/01/2006 to
3/31/2011.
NIH “Genomic Predictors of Arteriosclerosis in Hypertensives” Kardia-PI Period of Award 04/21/2007 to
03/31/2010
NIH “Michigan Center for Integrative Approaches to Health Disparities (CIAHD) Kardia –Coinvestigator, Period od Award 09/01/2007 to 08/31/2012
NIH “Genomic Approaches to Common Chronic Disease” Kardia-Co-investigator. Period of award
07/01/2007 to 06/30/2012
Kenneth M. Langa, Professor, Internal Medicine and Institute of Gerontology (2002)
Grants awarded
Blue Cross Blue Shield of Michigan Foundation. “Long-term Care Requirements of Elderly Patients
Undergoing Coronary Artery Bypass Grafting Surgery in Michigan,” K. M. Langa, PI. Period of award
1/03-12/03.
Hartford Foundation/Society for General Int. Med. “Collaborative Center for Research and Education in
the Care of Older Adults,” K. M. Langa, PI. Period of award 1/03-12/04
American Federation For Aging Research “Long-term Outcomes of Caring for a Disabled Spouse” Langa
KM-PI. Period of Award 07/01/2003 to 06/30/2006
NIH “Patterns and Predictors of Cognitive Decline” Langa, KM-PI
Period of Award 04/15/2006 to 03/31/2009
NIH “Health and Retirement Study” Weir-PI. Period of Award 01/01/2006 to 12/31/2011. RoleNIH “NIH Relationship of Frailty to Multimorbidity and Disability” Langa-Co-investigator
Period of Award 03/01/2006 to 02/29/2008.
NIH “Costs of Dementia” Langa-PI. Period of Award 09/01/2007 to 05/31/2012.
NIH “Ethics of Surrogate Consent for Dementia Research” Langa-Co-investigator.
Period of Award 09/15/2007 to 06/30/2011.
Honors, awards, promotions:
Paul Beeson Physician Faculty Scholars in Aging Research Award, KM Langa, PI. Period of award:
07/01/2003 to 06/30/2006.
Promoted to Associate Professor, Sept. 1, 2006.
Carmen Green, Professor, Anesthesiology (2002)
Grants Awarded
NIH-“ Neurochemistry of Opiate Abuse Risk in Chronic Pain” Zubieta-PI. Period od Award 09/30/2006
to 08/31/2011. Role, Co-PI
Blue Cross Blue Shield of Michigan Foundation, “Living with Cancer: The Quality of Cancer Pain
Management in African Americans”. C.Green, PI. Period of award: 12/01/2003 to 11/30/2005.
Robert Wood Johnson Foundation “Robert Wood Johnson Health Policy Fellowship”, Green-PI. Period
of Award 09/01/2006 to 08/31/2009
NIH-“ Chronic Pain in Cancer Survivors: Examining Disparities and Quality of Life” Green-PI. Period of
Award 04/01/2007 to 03/31/2010
Honors, awards, promotions:
• Promoted to Associate Professor of Anesthesiology with tenure
• Named one of the Top 100 Doctors by Consumer’s Checkbook
• Received the University of Michigan Harold R. Johnson Diversity Service Award
• Nominated for the American Pain Society’s Liebeskind Award
Jocelyn Wiggins, Associate Professor, Internal Medicine (Geriatrics) (2002)
Grants Awarded
NIH KO8, “The Aging Glomerulus”. J. Wiggins, PI. Period of award: 07/01/2004 to 06/30/2009.
Honors, awards, promotions:
• Promoted to Associate Professor of Internal Medicine
• Appointed Medical Director, Geriatrics Center Clinics & Turner Geriatric Clinic
Caroline Blaum, M.D., Professor, Internal Medicine (Geriatrics) (2003)
Grants Awarded
NIH R01, “Hyperglycemia, Frailty and Disability in Older Women”. C. Blaum, PI. Period of award:
09/01/2004 to 06/30/2007.
NIH “Relationship of Frailty to Multimorbidity and Disability” Blaum, CS, PI
Period of Award 03/01/2006 to 02/28/2008
NIH “Outcomes of Blood Pressure Management in Diabetes Patients with Comorbidities
09/30/2008 to 09/29/2010
American Diabetes Assn-“A Tailored Behavioral Intervention to Promote Physical Activity Adoption and
Maintenance for Older Adults with Type 2 Diabetes”. C. Blaum, Co-Investigator. Period of award
01/01/2006 to 12/31/2007.
VA PC-MH VA “Primary care Program Office and Demonstration Laboratories Merging Research and
Clinical Care’. Blaum, C.S., PI. Period of award: 4/10-3/15
NIH/AHRQ R24, “Clinical Database to Support Comparative Effectiveness Studies of Complex Patients”
Blaum, C.S., PI. Period of award:
9/10-8/12
CHRT, “Clinical Processes Related to Success in the Medicare Physician Group Practice Demonstration.”
Blaum, C.S. PI. Period of award: 7/10-6/12
NIH/NIA, “Claude D. Pepper Older Americans Independence Center. Pilot and Exploratory Study Core.”
J. Halter (PI). Period of award: 9/04-8/14
MICHR, “Impact of Care Continuity on Blood Pressure Trajectories in Complex Diabetes Patients” C.S.
Blaum, PI. Period of award: 9/09-9/11
NIH/AHRQ, “Impact of CMS Hospital-Acquired Conditions of Vulnerable Patients and Hospitals”
McMahon, PI. Period of award: 9/10-8/12.
Honors, awards, promotions:
Promoted to Associate Professor of Internal Medicine with tenure.
Promoted to Medical Director, Geriatrics Center Clinics & Turner Geriatric Clinic
Promoted to Professor of Internal Medicine
Carol Persad, Ph.D., Associate Professor, Division of Neuropsychology (2003-2005)
Grants Awarded
NIH “Neurobiology of the Menopausal Transition” Persad, CC-Co Investigator. Period of Award
06/01/2006 to 03/31/2010
Rachael Seidler, Ph.D., Associate Professor, Division of Kinesiology and Department of Psychology
(2003-2005)
Grants Awarded
NASA NBEI Award, UM Biomedical Engineering Department, 2003. Seidler, Co-Investigator Project 1
leader, “Neural and Neurovascular Changes in Simulated Microgravity”
NIH RO1 “Skill Acquisition in Older Adults” Seidler-PI, Period of Award 09/01/2005 to 07/31/2009
Gustavus and Louise Pfeiffer Foundation “Parkinson's Disease: Interactions Between Stage of Disease,
Treatment, and Motor and Cognitive Performance” Seidler-PI. Period of Award 01/01/2008 to
12/31/2008
NIH “Cortex Changes in Real / Imagined Movement in ALS (Amyotrophic Lateral Sclerosis)” Welsh-PI.
Period of Award 09/30/2007 to 05/31/2011. Role-Co-PI
Honors, awards, promotions:
Promoted to Associate Professor, 2009
Su-Hua Sha, M.D., Research Investigator, Kresge Hearing Research Center (2003)
Gilbert Gee, Ph.D., Associate Professor, Department of Health Behavior and Health Education,
School of Public Health, University of California, Los Angeles (2003-2004)
Grants Awarded
Peter F. McManus Charitable Trust “Drinking Trajectories of Aging Women” Gee-PI, Period of Award
01/01/2003 to 12/31/2003
Co-Principal Investigator (PI: Richard Lichtenstein). 2006-2007. Focus Groups Regarding Racial
and Ethnic Discrimination in Health Care Delivery. Walter J. McNearney Award
California Center for Population Research.Principal Investigator. 2008-2009. Accent and Name
Discrimination in Health Care: A Pilot Study.
National Institute of Mental Health. (5R13MH0824922-02) Co-Principal Investigator (PI: Margaret
Shih). 2008-2010. Culture and Mental Illness: RiskPrevention and Treatment in Asian Americans.
National Cancer Institute (1R21CA137297-01) Principal Investigator. 2009-2011. Understanding the Rise
of Obesity among Immigrants.
National Institute of Diabetes and Digestive and Kidney Diseases (RC1-DK-086038-01).
Co-Principal Investigator (PI: May Wang). 2009-2011. Agent-Based Model of Individual-Level
Food Choice and Physical Activity Behavior.
Gregory D. Cartee, Ph.D., Professor of Kinesiology (2004)
Grants Awarded
NIH “Aging, Calorie Restriction and Insulin Signaling” Cartee-PI, Period of Award 01/01/2004 to
04/30/2006.
NIH-“Skeletal Muscle Glucose Transport: Exercise and Insulin”, G. Cartee, PI. Period of Award
07/01/2006 to 05/30/2011.
NIH “Aging, Calorie Restriction and Insulin Signaling” Cartee-PI. Period of Award 07/01/2007 to
05/30/2012.
Honors, awards, promotions:
2005 Fellow, American Academy for Kinesiology and Physical Education (AAKPE)
Barbara McCreadie, Ph.D., Assistant Professor, Orthopedic Surgery (2004)
Grants Awarded
AFAR “Age-Related Response to Trabecular Bone Microdamage” McCreadie-PI , Period of Award
07/01/2004 to 06/30/2005.
Kimberlee Gretebeck, Ph.D., Assistant Professor, School of Nursing (2003-2005)
Grants Awarded
American Diabetes Association “A Tailored Behavioral Intervention to Promote Physical Activity
Adoption and Maintenance for Older Adults with Type 2 Diabetes” Gretebeck-PI, Period of Award
01/01/2006 to 12/31/2006.
Michigan Center for Health Intervention (MICHIN) pilot grant (P30 NR009000), Gretebeck, K.A., PI. A
Tailored Physical Activity Intervention to Improve Neuropathy and Mobility in Older Adults with Early
Diabetes. 2006-2007.
Blue Cross Blue Shield of Michigan Foundation “Worksite Screening and Education Program to Reduce
Hypertension in Michigan” Gretebeck-Co-Investigator, Period of Award 2006-2008.
John A. Hartford Foundation “The Influence of Environmental and Behavioral Determinants on Walking
in Older Adults” Gretebeck-PI, Period of Award 07/01/2007 to 8/31/2009.
James Harper, Ph.D., Research Investigator, Pathology (2006-2008)
Grants Awarded
American Federation for Aging Research, “Modulation of Stress Resistance and Aging in Mice,” Harper,
PI, Period of Award 07/01/2006 to 06/30/2008.
Nathan Shock Center, “Cellular and Molecular Biology of Aging: Administrative Supplement,” Harper,
Co-Investigator, Period of Award 9/15/2008 to 06/30/2009.
Allison Aiello, Ph.D., Associate Professor, Epidemiology, School of Public Health (2006-2008)
Grants Awarded
NIH “Reducing Transmission of Influenza by Face Masks” Monto-PI, Period of Award 09/30/2006 to
9/29/2008, Aiello, Co-PI.
5R01DA022720 “Ecologic Stressors, PTSD, and Drug Use in Detroit” Galea-PI, Period of Award
09/01/2007 to 8/31/2012, Aiello, Co-PI.
3R01DA022720-03S1 “Ecologic Stressors, PTSD, and Drug Use in Detroit” Period of Award 4/1/20108/31/2010.
NIH “Neighborhood cultural isolation and biomarkers of cardiovascular disease among Latinos” A.
Aiello-PI, Part of larger consortium grant P60 (PI: A. Diez-roux), Period of Award 09/01/07-08/31/12.
1R56DK087864“Life Course Socioeconomics, Acculturation, & Type-2 Diabetes Risk Among Latinos”
A. Aiello-PI, 5/1/2010-4/30/2011
1RC1MH088283 “Candidate Epigenetic Biomarkers For PTSD: Insights From Detroit” 9/30/20098/31/2010.
Annabelle Grolleau-Julius, Ph.D., Research Investigator, Internal Medicine (Geriatrics), left
University 2010 (2006)
Cindy Lustig, Ph.D., Associate Professor of Psychology, College of Literature, Science and the Arts
(2006)
Grants Awarded
NIH “Memory Training: Strategies Underlying Success and Transfer” Lustig-PI, Period of Award
09/15/2007 to 08/31/2009.
NSF “Acetylcholine, Cortex and Control” Lustig-PI, Period of Award 08/01/2007 to 02/28/2010
Honors, awards, promotions:
2009-10 Henry Russel Award
Allison Rosen, M.D., Ph.D., Associate Professor, University of Massachusetts Medical School,
Department of Quantitative Health Sciences (2006)
Grants Awarded
Harvard University “Development of National Health Accounts” Rosen-PI, Period of Award 07/01/2006
to 06/30/2007
HHS-NBER “NBER Center for Aging and Health Research”Rosen-PI, Period of Award 09/01/2007 to
06/30/2008
John A. Hartford Foundation, Center of Excellence in Geriatrics.
Gonzalo Garcia Ph.D., Research Investigator, Department of Pathology
Grants Awarded
American Federation for Aging Research, “Effects of Surface Glycosylation in the Age-related Decline of
T Cell Function” Gonzalo, PI. Period of Award 07/01/2003 to 06/30/2004.
NIH, “ERM and Rho Signal Pathways in T Cell Immune Senescence” Golzalo, PI. Period of Award
09/01/2007 to 08/31/2009.
NIH, “Activation Defects in T-Cells of Aged Mice” Gonzalo, Co-Investigator. Period of Award
09/01/2006 to 08/31/2007.
Pearl Lee M.D., Assistant Professor, Division of Geriatric Medicine, Department of Internal
Medicine (2008-2010)
Grants Awarded
John A. Hartford Foundation, Center of Excellence in Geriatrics. 7/1/2010-6/30/2011.
NIA: AG024824, University of Michigan Older Americans Independence Center; Pilot/Exploratory
Studies Core Diabetes Management and Physical Function of Older Adults
Role: Pilot project PI 07/01/2009- 06/30/2010.
Angela Subauste M.D., Clinical Assistant Professor, Division of Endocrinology, Department of
Internal Medicine (2008-2010)
Grants Awarded
John A. Hartford Foundation, Center of Excellence in Geriatrics, Pilot Grant. 7/1/2010-6/30/2011.
The University of Michigan OAIC, Pilot Grant “Modulation of Age Related Sarcopenia by Fatty Acids”
Subauste, PI, Period of Award 9/1/2008-8/31/2009.
University of Michigan Metabolomics and Obesity Center, Pilot Grant , “Role of AGPAT in obesity
induced insulin resistance” Subauste, PI, Period of Award 7/1/2007-6/30/2008.
Lan Yao Ph.D., RN, Assistant Professor, College of Nursing, Michigan State University (2008-2009)
Grants Awarded
Michigan Center for Health Intervention, Pilot Study Grant, “Effects of a positive emotion-charged Tai
Chi home program on mobility, balance, and fall risks in elders with Alzheimer’s disease: a pilot
controlled trial” Yao (Pilot PI), Period of Award 05/01/2007-04/30/2009.
American Academy of Nursing/John A. Hartford Foundation, Claire M. Fagin Postdoctoral Fellowship
“Effects of a positive emotion-charged Tai Chi home training program on elders with Alzheimer’s
Disease and their caregivers” Yao (Awardee), Period of Award 07/01/2006-12/31/2008.
University of Michigan Integrative Health Care Pilot Research Grant, “Feasibility of a positive emotioncharged Tai Chi home training program and its effects on patients with dementia and caregivers,” Yao
(Pilot PI), Period of Award 12/01/2006-11/30/2008.
University of Michigan Office of the Vice President for Research Pilot Research Grant, “Impact of Social
Interactions on Locomoting Behaviors of Elders with Dementia: A Pilot Study using Noldus Observer”
Yao (Pilot PI), Period of Award 07/01/2005-06/30/2006.
Sara Wright Ph.D., Clinical Lecturer, Department of Psychiatry (2008)
VA Career Development Award, Level One, “The Role of Psychological Factors in Predicting Fall Risk
in Elders,” (Wright), 9/2008-9/2010, Principal Investigator
Michigan Institute for Clinical and Health Research Pilot Grant Fund, “The Role of Cognitive and
Affective Factors in Explaining Increased Risk of Falls among Patients with Geriatric Depression,”
(Wright), 1/2009-09/2011, Principal Investigator
Jack L. Berman, M.D. and Barbara A. Berman, Ph.D. Depression Research Fund Award (Geriatric
Depression), University of Michigan Department of Psychiatry Depression Center, “The Role of
Cognitive and Affective Variables in Explaining Increased Risk of Falls among Patients with Geriatric
Depression,” (Wright), 5/2008- 9/2010, Principal Investigator
Meader Research Fund for Depression/Genetics/Pain, University of Michigan Department of Psychiatry
Depression Center, “Neurobiological Measures of Lifetime Depression Burden: Stability and
Relationship with Treatment Status,” (Langenecker/Wright), 01/2008- 01/2011, Co-Principal Investigator
Michigan Alzheimer’s Disease Research Center Pilot Grant Fund, “Investigation of Neuroanatomical
Networks to Understand Late Onset Depression,” (Langenecker/Wright), 6/2009-06/2011, Co-Principal
Investigator
VA Career Development Award, Level Two, “Cognitive, Clinical, and Neural Markers of Late Life
Depression,” (Wright), Principal Investigator, Intent to Award Letter Received.
Kara Zivin Ph.D., Assistant Professor, Department of Psychiatry, (2008)
Grants Awarded
Blue Cross Blue Shield of Michigan Foundation, “Implementation of a Depression Stepped Treatment
Protocol and Management System for Cardiovascular Patients” Zivin, Co-Investigator, 12/01/2007 to
11/30/2008
VA CDA-1 examining the relationship between depression and older adult workforce participation
Anjali Desai Ph.D., Project Manager, Trialynx Inc. (2008-2010)
Grants Awarded
University of Michigan Cardiovascular Center McKay Grant “The role of nitric oxide in erythropoietinmediated atherosclerosis in chronic kidney disease” Desai (PI), 6/1/08-5/31/09.
American Heart Association Scientist Development Grant, “Role of erythropoietin and iron therapy in the
development of atherosclerosis in chronic renal disease,” Desai (PI), 1/1/03-12/31/05.
Renal Research Institute Grant “Role of Alpha-Tocopherol (Vitamin E) in reducing oxidative Stress,
Endothelial Dysfunction and Advanced Glycosylation End Products in Chronic Renal Insufficiency: a
Pilot Study”Saran, PI ; Desai Co-Investigator, 9/1/01-3/30/06.
Amir Sadghi-Akha M.D., Ph.D., Research Investigator, Department of Pathology (2009)
Tanya Gure MD, Assistant Professor, Department of Internal Medicine (2009-2010)
Grants Awarded
John A. Hartford Foundation, Center of Excellence in Geriatrics, Pilot Grant. 7/1/2010-6/30/2011.
MICHR KL2, “The prevalence of cognitive impairment among older adults with heart failure” 7/1/108/31/11
SECTION IV. PUBLICATIONS: Provide only those that are a direct result of Pepper Center resources
and list publications published in the 2010 funding year only (9/1/10 – 8/31/11).
Anguera, J. A., Reuter-Lorenz, PA., Willingham, D. T., & Seidler, R. D. (2011). Failure to engage spatial
working memory contributes to age-related declines in visuomotor learning. Journal of Cognitive
Neuroscience, 23(1): 11-25. PMC Journal - in progress.
Banaszak-Holl J., Liang J., Quinones A., Cigolle C.T., Lee I., Verbrugge L.M. Trajectories of functional
change among long-stayers in nursing homes: Does baseline impairment matter? Journal of Aging and
Health. PMC Journal – in progress.
Botoseneanu, A. & Liang, J. (2011). Social stratification of body-weight trajectory in middle aged and
older Americans: Results from a 14-year longitudinal study. Journal of Aging and Health. 23(3), 454480. NIHMSID 303323.
Cigolle C.T., Lee P.G., Langa K.M., Lee Y., Tian Z., Blaum C.S. Geriatric conditions develop in middleaged adults with diabetes. Journal of General Internal Medicine 26(3): p. 272-9, 2011. PMCID:
PMC3043187.
Fling, B. W., Chapekis, M., Reuter-Lorenz, P. A., Anguera, J. A., Bo, J., Langan, J., Welsh, R.
C., & Seidler, R. D. (in press). Age differences in callosal contributions to cognitive processes.
Neuropsychologia. PMCID: PMC3137668.
Fling, B. W., Walsh, C. M., Bangert, A. S., Reuter-Lorenz, P. A., Welsh, R. C., & Seidler, R. D.
(in press). Differential callosal contributions to bimanual control in young and older adults.
Journal of Cognitive Neuroscience. PMC Journal - in progress.
Funkhouser E, Houston TK, Levine DA, Richman J, Allison JJ, Kiefe CI. Physician and patient
influences on provider performance: beta-blockers in postmyocardial infarction management in the MIPlus study. Circ Cardiovasc Qual Outcomes. 2011;4(1):99-106.
Garcia, G. G. and R. A. Miller. 2011. Age-related defects in the cytoskeleton signaling pathways of CD4
T cells. Ageing Research Reviews 10:26-34. PMCID: PMC2888705.
Garcia, G. G., and R. A. Miller. 2011. Ex vivo enzymatic treatment of aged CD4 T cells restores
antigen-driven CD69 expression and proliferation in mice. Immunobiology. 216:66-71. PMCID:
PMC2908212.
Harper, J. M., M. Wang, A. T. Galecki, J. Ro, J. B. Williams and R.A. Miller. Fibroblasts from longlived bird species are resistant to multiple forms of stress. 2011. J. Experimental Biology. PMCID:
PMC3092728.
Karve SJ, Balkrishnan R, Mohammad YM, Levine DA. Racial/ethnic disparities in emergency
department waiting time for stroke patients in the United States. J Stroke Cerebrovasc Dis.
2011;20(1):30-40. PMC Journal – in progress.
Kelley-Quon L, Min L, Morley E, Hiatt J, Cryer H, Tillou A. Functional status after injury: A
longitudinal study of geriatric trauma. The American Surgeon, 2010; 76(10): 1055-8. [Revision and
publication after appointment]. NIHMS307812.
Lakoski SG, Lee AH, Muntner P, Judd SE, Safford MM, Levine DA, Howard G, Cushman M. Adiposity,
inflammation, and risk of death in black and white men and women in the US: the REGARDS study.
Journal of Clinical Endocrinology & Metabolism. 2011;96(6):1805-14. Epub 2011 Mar 23. PMCID:
PMC3100756.
Lee, B. C., Chen, S., Sienko, K. H. A wearable device for real-time motion error detection and
vibrotactile instructional cuing. In press, IEEE Transactions on Neural Systems and Rehabilitation
Engineering. PMC Journal – in progress.
Lee YJ and Ashton-Miller JA. The Effects of Gender, Level of Co-Contraction and Initial Angle
on Elbow Extensor Muscle Stiffness and Damping under a Step Increase in Elbow Flexion
Moment, Annals of Biomedical Engineering (In press).
Levine DA, Calhoun DA, Prineas RJ, Cushman M, Howard VJ, Howard G. Moderate waist
circumference and hypertension prevalence: the REGARDS study. Am J Hypertens. 2011;24(4):482-8.
Epub 2011 Jan 13. PMC Journal – in progress.
Levine DA, Lewis CE, Williams OD, Safford MM, Liu K, Calhoun DA, Kim Y, Jacobs DR, Jr., Kiefe CI.
Geographic and demographic variability in 20-year hypertension incidence: the CARDIA study.
Hypertension. 2011;57(1):39-47. PMCID: PMC3057218.
Levine DA, Neidecker MV, Kiefe CI, Karve S, Williams LS, Allison JJ. Racial/ethnic disparities in
access to physician care and medications among US stroke survivors. Neurology. 2011;76(1):53-61.
PMCID: PMC3030224.
Levine DA, Langa KM. Vascular cognitive impairment: disease mechanisms and therapeutic
implications. Neurotherapeutics. Epub 2011 10 May. DOI: 10.1007/s13311-011-0047-z.
Liang, J., Wang, C.N., Xu, X., Hsu, H.C., Lin, H.S., & Lin, Y.H. (2010). Trajectory of functional
status among older Taiwanese: Gender and age variations. Social Science & Medicine, 71,
1208-1217. NIHMS226188.
Liang, J., Xu, X., Ye, W., Bennett, J. & Quiñones, A. R. (in press). Multiple trajectories of
depressive symptoms in middle and late life: Ethnic variations. Psychology and Aging,
PMC Journal – In Process.
Miller, R. A., D. Dolan, M. Han, W. Kohler, and J. Schacht. 2011. Resistance of skin fibroblasts to
peroxide and UV damage predicts hearing loss in aging mice. Aging Cell. doi: 10.1111/j.14749726.2010.00668.x PMCID: PMC3079202.
Miller, R. A., J. Kreider, A. Galecki, and S. A. Goldstein. 2011. Preservation of femoral bone thickness
in middle age predicts survival in genetically heterogeneous mice. Aging Cell. doi: 10.1111/j.14749726.2011.00671.x PMCID: PMC3094489.
Miller, R. A., D. Harrison, C. M. Astle, J. A. Baur, A. R. Boyd, R. de Cabo, E. Fernandez, K. Flurkey,
M. A. Javors, J. F. Nelson, C. J. Orihuela, S. Pletcher, Z. D. Sharp, D. Sinclair, J. W. Starnes, J. E.
Wilkinson, N. L. Nadon, and R. Strong. 2011. Rapamycin, but not resveratrol or simvastatin, extends
lifespan of genetically heterogeneous mice. J Gerontol A Biol Sci Med Sci. 66: 191-201. PMCID:
PMC3021372.
Min L, Reuben DB, Shekelle PG, Keeler E, Ganz DA, Fung C, Solomon, DH, Roth CP, Stevens
M, Young RT, Wenger NS. Is greater severity of a geriatric condition related to better quality of
care? Medical Care 2011; 49(1): 101-7. PMID: 21079526
Min L, Reuben D, Adams J, Shekelle P, Ganz D, Roth C, Wenger N. Does better quality of care
for falls and urinary incontinence result in better patient-reported outcomes? J Am Geriatr Soc,
in press.
Min L, Ubhayakar N, Saliba D, Kelley-Quon L, Morley E, Hiatt J, Cryer H, Tillou A, The
Vulnerable Elders-13 Survey predicts hospital complications and mortality among geriatric
trauma patients. J Am Geriatr Soc, in press.
O’Brien JM, Lu B, Ali NA, Levine DA, Aberegg SK, Lemeshow S. Insurance type and sepsis-associated
hospitalizations and sepsis-associated mortality among U.S. adults: a retrospective cohort study. Critical
Care. 2011;15:R130. Epub 23 May 2011. doi:10.1186/cc10243.
Panici, J. A., J. M. Harper, R. A Miller, A. Bartke, A. Spong, and M. M. Masternak. 2010. Early life
growth hormone treatment shortened the longevity and decreased cellular stress resistance in long-living
mice. FASEB Journal 24: 5073 – 5079. PMCID: PMC2992365.
Ramaswamy K.S., Palmer M.L., van der Meulen J.H., Renoux A., Kostrominova T.Y., Michele D.E.,
Faulkner J.A.,” Lateral transmission of force is impaired in skeletal muscles of dystrophic mice and
oldest-old rats”, J. Physiology – London (in press).
Shaw, B.A., Liang, J., Krause, N., Gallant, M.P. & McGeeve, K. (2010). Age differences and social
stratification in the long-term trajectories of leisure-time physical activity. Journal of Gerontology:
Social Sciences. 65B(6): 756-766. PMCID: PMC2954334.
Staskin D, Tubaro A, Norton PA, Ashton-Miller JA. Mechanisms of Continence and Surgical Cure in
Female and Male SUI: Surgical Research Initiatives, ICIRS 2010. Neurourology and Urodynamics. 2011,
30 (5):704-7. PMC Journal – in progress.
Sun, L. Y., A. F. Bokov, A. Richardson, and R. A. Miller. 2011. Hepatic response to oxidative injury:
qualitative differences in long-lived Ames dwarf mice. FASEB Journal 25:398-408. PMCID:
PMC3005438.
Wright, S.L., Kay, R.E., Avery, E.T., Giordani, B., & Alexander, N. A. The impact of
depression on dual tasking among patients with high fall risk. Journal of Geriatric Psychiatry and
Neurology. 2011.
Young JG, Woolley C, Ashton-Miller JA, Armstrong TJ. The Effect of Handhold Orientation, Size, and
Wearing Gloves on Hand/Handhold Breakaway Strength. Human Factors (In Press)
Zilliox L, Peltier AC, Wren PA, Anderson A, Smith AG, Singleton JR, Feldman EL, Alexander NB,
Russell JW. Assessing autonomic dysfunction in early diabetic neuropathy: the Survey of Autonomic
Symptoms. Neurology. 76(12):1099-105, 2011. PMCID: PMC3068012.
Zulman D.M., Sussman J.B., Chen X., Cigolle C.T., Blaum C.S., Hayward R.A. Examining the
evidence: a systematic review of the inclusion and analysis of older adults in randomized controlled trials.
Journal of General Internal Medicine. 2011 Jul. 26(7): 783-90. PMC Journal – in progress.
BOOK CHAPTERS, REVIEWS AND SOLICITED ARTICLES
Alexander NB. Gait disorders. In: Pacala JT, Sullivan GM, eds. Geriatrics Review Syllabus: A Core
Curriculum in Geriatric Medicine, 7th ed. New York, NY: American Geriatrics Society; 2010.
Mariano J, Min L. “Functional Status and Co-morbidity”, Management of Cancer in the Older
Patient, eds Arash N, Reuben D, Ganz P, in press.
University of Michigan
Claude D. Pepper Older Americans Independence Center
Recognition and Awards: Prize or honors, NOT grant awards, should be a listing of all major
scientific awards received by your center’s personnel in 2010.
Jeffrey B. Halter, M.D., was invited Visiting Professor, Course on Vascular Disease Risk in
Diabetes, Escuela Superior de Formación Académica en Geriatría, Segovia, Spain.
Richard A. Miller, M.D., Ph.D., was the recipient of the Senior Scholars in Aging Research
Award from the Ellison Medical Foundation.
Caroline Vitale, M.D. was the recipient of the American Geriatrics Society Special Recognition
Award for Outstanding Service on the AGS Ethics Committee
University of Michigan
Claude D. Pepper Older Americans Independence Center
Minority Research: List activities with minority trainees and research focusing on hypotheses
dealing with minority health. Clinical research that has an expected number of minority subjects
(a NIH requirement) is NOT what is desired for this section. Only work that has a comparison of
minority members to majority members such as work on health disparities should be included.
Minority Trainee(s):
Manuel Hernandez, a Ruth L. Kirschstein National Research Service Awardee (NIA AG024689)
and biomedical engineering doctoral student co-mentored by Neil B. Alexander (Director,
Mobility Research Center) and James A. Ashton-Miller (Director, Biomechanics Research
Laboratory) is working on the mechanisms underlying control of the trunk during challenging
balancing tasks in the elderly.
Ana Quinones, doctoral student in the School of Public Health mentored by Jersey Liang
(Director, Human Subjects and Assessment Core) completed her doctoral dissertation, Essays on
Race/Ethnic Variations in the Dynamics of Chronic Disease in Middle and Older Age
Americans.. (NIA AG029783: Ethnic Trajectories of Aging).
Tanya Gure MD, Assistant Professor, Department of Internal Medicine, completed the Robert
Wood Johnson Clinical Scholars Program and the Fellowship in Clinical Geriatrics at UM. Her
goal is to determine the prevalence of cognitive impairment among older adults with heart failure
and its impact on morbidity and mortality. She is co-mentored by Caroline Blaum, MD, MS,
Professor & Associate Chief, Division of Geriatric Medicine and researcher in disability,
nutrition, transitional care and diabetes in elderly, and Ken Langa MD, PhD, Professor in
General Medicine and researcher in health care in dementia, and who was an RCDC Research
Retreat participant and NIA Beeson awardee. Dr. Gure was also funded in 2008 with a PESC
pilot award. She is a recent RCDC awardee. She is also an awardee of a MICHR KL2 award.
2007-2009 Diversity Supplement awardee; 3R01AG027010-02S1 Langa (PI), Patterns and
predictors of cognitive decline.
2008-2009 OAIC pilot grant funding. Project Title: The prevalence of cognitive decline in older
adults with chronic heart failure.
Funded Research:
R56DK087864-01, Allison Aiello (PI) Life Course Socioeconomics, Acculturation, & Type-2
Diabetes Risk Among Latinos.
3R01AG027010-02S1 Langa (PI) Patterns and predictors of cognitive decline 2007-2009
Diversity Supplement awardee.
Research Articles:
Liang, J., Xu, X., Bennett, J.M., Ye, W. & Quiñones, A.R. (2010). Ethnicity and changing
functional health in middle and late life: A person-centered approach. Journal of Gerontology:
Social Sciences, 65B(4), 470-481. PMCID: PMC2883869.
Xu, X., Liang, J., Bennett, J.M., Quiñones, A.R. & Ye, W. (2010). Ethnic differences in the
dynamics of depressive symptoms in middle aged and older Americans. Journal of Aging and
Health. 22(5), 631-52. PMCID: PMC2896431.
Shaw, B.A., Liang, J., Krause, N., Gallant, M.P. & McGeeve, K. (2010). Age differences and
social stratification in the long-term trajectories of leisure-time physical activity. Journal of
Gerontology: Social Sciences. 65B(6): 756-766. PMCID: PMC2954334.
Liang, J., Xu, X., Ye, W., Bennett, J. & Quiñones, A. R. (in press). Multiple trajectories of
depressive symptoms in middle and late life: Ethnic variations. Psychology and Aging, PMC
Journal – In Process.
Botoseneanu, A. & Liang, J. (2011). Social stratification of body-weight trajectory in middle
aged and older Americans: Results from a 14-year longitudinal study. Journal of Aging and
Health. 23(3), 454-480. NIHMSID 303323.
Conference Presentations:
Quiñones, A. R. , Liang, J, & Ye, W. (2010). Risk of incident hypertension among Black, White,
and Mexican Americans after age 50. Presented at the 63rd Annual Meeting of the Gerontological
Society of America, New Orleans.
Liang, J., Fultz, N., Bennett, J. M., Shaw, B. & Krause, N. (2010). Assimilation and trajectories
of positive and negative affect among older Mexican-Americans. Presented at the 63rd Annual
Meeting of the Gerontological Society of America, New Orleans.
Hernandez, M.E., Ashton-Miller, J.A., & Alexander, N.B. (2011). Forward dynamic model of
the momentum arrest phase of whole-body downward reaching movements: Effects of age and
functional impairment. Proceedings of the 21st Annual Meeting of the Society for the Neural
Control of Movement, San Juan, Puerto Rico.
Hernandez, M.E., Ashton-Miller, J.A., & Alexander, N.B. (2010). An experimental study of
postural control during downward reach and pick-up movements: Effects of age and limiting the
length of the base of support. Proceedings of the 34th Annual Meeting of the American Society
of Biomechanics, Providence, RI
Hernandez, M.E., Ashton-Miller, J.A., & Alexander, N.B. (2010).Discrete, accuracyconstrained, center of pressure movements near the limits of the functional base of support:
effects of age and movement direction. Proceedings of the 20th Annual Meeting of the Society
for the Neural Control of Movement, Naples, FL.
University of Pittsburgh
Older American’s Independence Center
2009-2010 Directory
Contact Information:
Program Director:
Stephanie Studenski, MD, MPH
3471 Fifth Avenue; Suite 500
Pittsburgh, PA 15213
(412) 692-2361
(412) 692-2370 fx.
[email protected]
Program Administrator:
Nichole Radulovich
3471 Fifth Avenue; Suite 500
Pittsburgh, PA 15213
(412) 692-2375
(412) 692-2370 fx.
[email protected]
Senior Administrator:
Nichole Radulovich
3471 Fifth Avenue; Suite 500
Pittsburgh, PA 15213
(412) 692-2375
(412) 692-2370 fx.
[email protected]
Section I. Description of Center
Balance disorders in older persons are common, disabling and complex. In order to
prevent and treat these disorders, a concentrated, multidisciplinary effort to understand
causes and consequences, and to develop innovative treatments, is needed. The team of
investigators at Pittsburgh offers complementary expertise, outstanding research
productivity, and ongoing studies to address this need through a Claude D. Pepper Older
Americans Independence Center. This program includes faculty from 5 Schools;
medicine, nursing, public health, allied health, and engineering.
The Specific Aims of the Pittsburgh Claude D. Pepper Center are to 1) develop
interventions to improve function and independence in older adults with balance
disorders, 2) integrate studies of physiologic, biomechanical and psychosocial
mechanisms affecting balance with clinical studies, and 3) foster multidisciplinary
research and research training. The Program has 6 Cores (Leadership/Administration
Core, Pilot Exploratory Core, Research Career Development Core, Clinical Core,
Technology Core, and Data Management and Analysis Core. The program integrates 15
independently funded studies. Training support is provided directly to Pepper Scholars
and also to trainees in related programs.
The long range goals of the Program are to 1) incorporate effective interventions to
maintain or improve balance, and reduce the negative consequences of balance disorders,
into usual clinical care and wellness programs in diverse health care and community
settings and 2) further define an evidence-based differential diagnosis of contributors to
balance disorders that can be used in clinical practice for prevention and treatment.
Section II. Research, Resources and Activities
A.
Primary Cores
LAC (Stephanie Studenski, MD, MPH)The Leadership Administration Core is responsible for the overall coordination,
monitoring, compliance and reporting functions of the OAIC. It promotes internal
coordination, institutional interactions and external relationships. It supports the External
Advisory Committee and sponsors a seminar series, annual retreat, website, publications
committee, visiting professor series, topical workgroups, grant planning retreats and
national and local conferences.
PESC (Stephanie Studenski, MD, MPH)The Pilot/Exploratory Studies Core promotes innovative multidisciplinary
research related to balance, mobility, falls and aging. It manages promotion, application,
review, award, monitoring and subsequent tracking for pilot proposals and for
developmental projects. Criteria for funding include relevance to the OAIC mission, new
multidisciplinary co