68th Annual Scientific Meeting
organelles responsible for generating energy in the cell. These
papers were chosen by a program committee that evaluates
the quality of the work and its relevance to the GSA themes;
the presenters receive a travel award.
MITOQ SUPPLEMENTATION IMPROVES MOTOR
FUNCTION AND MUSCLE MITOCHONDRIAL
HEALTH IN OLD MALE MICE
J.N. Justice1, D.R. Seals2, M.L. Battson2, J.J. Herrera2, M.P.
Murphy3, R. Gioscia-Ryan2, 1. University of Colorado
Boulder, Boulder, Colorado, 2. Department of Integrative
Physiology, University of Colorado Boulder, Boulder,
Colorado, 3. MRC Mitochondrial Biology Unit, Cambridge,
United Kingdom
The mechanisms underlying the development of motor
dysfunction with aging are incompletely understood, but a
compelling hypothesis is that age-related increases in mitochondria-derived reactive oxygen species (mtROS) may
contribute. To determine the role of excessive mtROS in ageassociated motor dysfunction, we tested the hypothesis that
supplementation with MitoQ, a mitochondria-specific antioxidant, would enhance motor function in older C57Bl/6.
Motor function was assessed using a battery of tests in
young (4-mo) and old (26-mo) mice at baseline and after 4
weeks of MitoQ or vehicle (n=20/group). MitoQ improved
mass normalized grip-strength (+23.1%) and completely
restored endurance rota-rod-run time (+95.2%) and distance
(+69.1%) in old animals supplemented with MitoQ but not
old control or young male mice. These were accompanied an
improvement in markers of mitochondrial health, including
protein expression of SIRT-3, MnSOD, VDAC in the skeletal
muscle of a subset of mice.
AMBIENT TEMPERATURE ENERGETIC CHALLENGE
IMPROVES HEALTHSPAN IN MALE C57BL/6 MICE
V.K. Gibbs, D.L. Smith, D.B. Allison, T. Nagy, University of
Alabama at Birmingham, Birmingham, Alabama
To emulate the energetic conditions of caloric restriction, a state of energetic insecurity in mice was induced by
increasing energy expenditure through lowered housing
temperature while not allowing energy intake to increase to
compensate. We hypothesize that the mice which perceive
an energy limitation will live longer, healthier lives. At 12
weeks of age, 160 male C57BL/6 mice were randomized to
individual housing at either 22°C or 27°C. Mice at 27°C
(near thermoneutrality) were fed ad libitum, and mice at
22°C were pair-fed to mice at 27°C (representing approximately 30% caloric restriction). Mice at 27°C had higher
body, fat, and lean mass than mice at 22°C (p<0.0001).
However, mice at 27°C had lower maximum grip strength
at 74 (p<0.0001) and 87 (p<0.0001), but not at 98 weeks
(p=0.1655). Total motor-health assessment scores were
poorer for mice at 27°C than mice at 22°C at 68 (p=0.0058)
and 76 (p=0.0004), but similar at 88 weeks (p=0.1185).
Survival for the both groups was >96% by age 75 weeks
and remained at 95% for the 22°C group by age 100 weeks
but declined to 80% the 27°C group. While this longevity
study is ongoing, healthspan metrics suggest age-related
declines in skeletal muscle strength and motor function may
be attenuated for mice at 22°C who face a greater energetic
demand, relative to those at 27°C.
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RELATIONSHIPS BETWEEN BLOOD BIOENERGETIC
CAPACITY AND FAT LOSS AFTER DIET AND
EXERCISE INTERVENTION
D.J. Tyrrell, M.S. Bharadwaj, C.G. Van Horn, B. Nicklas,
A.J. Molina, Geriatrics and Gerontology, Wake Forest
School of Medicine, Winston Salem, North Carolina
Background: Thigh intermuscular adipose tissue (IMAT)
is associated with lower strength and power and strongly predicts physical function decline and mobility disability onset in
aging. Blood bioenergetic capacity is also related to strength
and physical function and is negatively affected by adiposity.
Resistance exercise training (RT) and RT with weight loss
(RT+WL) have recently been shown to reduce IMAT and
improve strength and physical function. This study tested the
hypothesis that peripheral blood mononuclear cell (PBMC)
bioenergetic capacity may be related to adiposity at baseline
and after intervention. Methods: Community-dwelling, wellfunctioning, overweight/obese (BMI, 25-35), older adults
(≥65yrs) were randomized to RT (n=6) or RT+WL (n=5).
PBMC Basal, maximal, and spare respiration were measured
using a Seahorse XF-24 respirometer and compared with
adiposity via computed tomography resulting from interventions. Results: Baseline PBMC bioenergetic capacity did not
significantly correlate with baseline IMAT; however, baseline
PBMC bioenergetic capacity associated with IMAT change
after RT and RT+WL intervention, independent of baseline
IMAT and group assignment (maximal respiration: R=0.66,
p≤0.05; basal respiration: R=0.72, p≤0.05). Future studies
are required to determine if PBMC bioenergetics predicts
individual response to RT or WL. Conclusions: Blood-based
bioenergetic profiling provides a minimally invasive, objective measure of bioenergetic capacity and has been proposed
as a reporter for systemic mitochondrial function. Our results
indicate that PBMC bioenergetic capacity may provide a predictive measure of responses to diet and exercise intervention, particularly in IMAT, which is known to detrimentally
impact muscle function and mobility.
MAINTENANCE OF GLUTATHIONE REDOX
STATUS IN THE NAKED MOLE-RAT HEART UNDER
CONDITIONS OF HIGH OXIDATIVE STRESS
K.M. Grimes1,2, R. Buffenstein1,2, 1. Sam and Ann Barshop
Institute for Aging and Longevity Studies, University of
Texas Health Science Center at San Antonio, San Antonio,
Texas, 2. Department of Physiology, University of Texas
Health Science Center at San Antonio, San Antonio, Texas
Naked mole-rats (NMRs) can attain a maximum lifespan
of 32 years and are able to maintain cardiovascular function for at least 75% of this extraordinary longevity. This is
highly unlike all other mammals studied to date, which experience cardiovascular declines by at least mid-age. Oxidative
stress is largely implicated in both the development of cardiovascular disease and its greatest risk factor, advancing age.
Therefore we sought to test the hypothesis that resistance to
oxidative stress allows the NMR to maintain cardiovascular
function. We treated NMRs and mice with a large bolus of
doxorubicin (DOX; 20 mg/kg), a potent cardiac oxidative
stressor. Echocardiography showed that 7 days after DOX
treatment mice had a significant 25% decline in cardiac
contractility, whereas NMRs maintained heart function. We
found that DOX caused an increase in reduced glutathione