15
20
ce
er
en
on
f
C
BG
S
Sp
rin
g
Sarcopenia: causes, consequences
and strategies
Dr Helen Roberts
email [email protected]
15
ce
20
Declaration of sponsorship
BG
S
Sp
rin
g
C
on
f
er
en
• Boehringer, GSK, Lundbeck, Orion, Novartis,
Teva, UCB
S
Sp
rin
g
C
on
f
er
en
15
What is sarcopenia
Why does it matter
What causes it
How is it diagnosed
What are the consequences of sarcopenia
A lifecourse approach to the prevention and
management of sarcopenia
BG
•
•
•
•
•
•
ce
20
Outline of talk
S
Sp
rin
g
C
on
f
• Loss of skeletal
muscle mass and
function associated
with increasing age
er
en
• ‘poverty of flesh’
BG
15
20
ce
Sarcopenia
15
20
ce
Sp
rin
g
C
on
f
er
en
“The sixth age shifts
Into the lean and slipper’d pantaloon
With spectacles on nose and pouch on side,
His youthful hose well sav’d, a world to wide
For his shrunk shank”
BG
S
Shakespeare, As You Like It, Act II, Scene VII, lines 157–161
S
BG
rin
g
Sp
on
f
C
ce
er
en
15
20
15
ce
20
Operational definition of sarcopenia
er
en
• European Working group on Sarcopenia
Cruz-Jentoft Age Ageing (2010) 39: 412
Sp
rin
g
C
on
f
• Progressive generalised loss of skeletal muscle
mass and strength with age
• Diagnosis based on low muscle mass and low
muscle function (strength or performance)
BG
S
• Similar definition by US working group
Fielding JAMDR (2011)12: 249
15
ce
20
Why does sarcopenia matter?
BG
S
Sp
rin
g
C
on
f
er
en
• Common
• associated with current and future frailty,
disability, morbidity and mortality
• associated with major co-morbidity such as
osteoporosis, obesity and type 2 diabetes
• it predicts future mortality in middle-aged as well
as older adults
• estimated direct healthcare cost in the USA in
2000 was £18.5 bn
15
er
en
ce
Catabolic
•Hormones eg
glucagon, steroids
•Inflammatory mediators
eg cytokines
•Growth inhibitor protein
myostatin
•Obesity
•Chronic inflammation
through IL6 and TNFα
BG
S
Sp
rin
g
C
on
f
Anabolic
• Hormones eg insulin,
testosterone
• Growth factors eg
growth hormone
• Vitamin D
• Physical activity
• Protein consumption
20
Maintenance of muscle mass
ce
20
15
Factors influencing the decrease in
muscle mass with age
BG
S
Sp
rin
g
C
on
f
er
en
• anabolic resistance of older skeletal muscle to
dietary protein and amino acids
• oxidative damage from an accumulation of
reactive oxygen species
• reduced myofibre innervation
• Low grade inflammation promotes muscle
degeneration
15
20
Changes in muscle with age
BG
S
Sp
rin
g
C
on
f
er
en
ce
• type 1 myofibres - slow contraction time, utilise oxidative
pathways and resist fatigue
• type 2 myofibres - quick contraction time, rely on
glycolytic pathways and fatigue more easily
• Between 20 to 80 years of age ~ 30% reduction in
muscle mass and a decline in cross-sectional area of
about 20%
• decline in both muscle fibre size and number
• Within the muscle, there is a decrease in non-contractile
area along with a decrease in cross-bridging between
the fibres
• Single fibre intrinsic force is decreased.
15
S
Sp
rin
g
C
on
f
er
en
Older age
Sedentary lifestyle
Low dietary intake of protein and amino acids
Obesity
Inflammation
Co-morbidities eg diabetes
Low birth weight
Low pre-pubertal and pubertal growth
BG
•
•
•
•
•
•
•
•
ce
20
Risk factors for sarcopenia
15
ce
20
Sarcopenia and osteoporosis
BG
S
Sp
rin
g
C
on
f
er
en
• 313 men and 318 women from the HCS had
assessment of muscle mass & function with
bone size, density & strength
• Muscle size and grip strength (but not gait
speed) were associated with bone size and
strength
• supporting evidence for a functional musclebone unit in which bone health may be directly
influenced by muscle function
Edwards M. J Bone Miner Res (2013) 28:2295
15
ce
20
Identification of patients at risk
BG
S
Sp
rin
g
C
on
f
er
en
• Noted decline in function, strength, “health”
status
• Self-reported mobility-related difficulty
• History of recurrent falls
• Recent unintentional weight loss (> 5%)
• Post-hospitalization
• Long term conditions eg: Type II diabetes,
chronic heart /kidney failure, COPD, RA and
Cancer
ce
20
15
Diagnosis of sarcopenia
on
f
er
en
Loss of muscle mass and function with age
Low muscle
function
C
Low muscle
mass
BG
S
Sp
rin
g
• Low strength
• Low physical
performance
Sarcopenia
ce
20
15
Diagnosis of sarcopenia
er
en
• Slow gait speed over 4 m (<0.8 m/second)
rin
g
C
on
f
• Muscle strength: grip strength
• <20kg women, <30 kg men EWGSOP
• <16kg women, <26kg men FNIH USA
BG
S
Sp
• Muscle mass – DXA, bio-impedance
• ALM/ht2 EWGSOP
• ALM:BMI ratio FNIH
20
15
Standardised measurement of grip
strength
C
on
f
• Seated in upright chair
with elbows supported
er
en
ce
• Calibrated Jamar
dynamometer
Sp
rin
g
• Maximum value from
three attempts with each
hand 1 minute apart
BG
S
• Standard encouragement
Roberts HC Age Ageing (2011) 40: 423
20
15
Acceptability of grip strength assessment to older
people in healthcare settings
er
en
ce
• The grip seemed to be quite a central arrangement. It suited my hand
anyway. 4 (inpatient)
C
on
f
• I think most people would be good at it, don’t you? Unless they had
arthritis in their wrist or something like that. 21(community
physiotherapy)
Sp
rin
g
• No hardship to test it, only takes a few minutes. 19 (nursing home)
BG
S
Roberts Journal Aging Research and Clinical Practice (2012) 1:135
15
ce
20
Prevalence of sarcopenia
on
f
er
en
• Depends on population sampled and criteria
used
• Hertfordshire cohort 4.6% men and 7.9% women
aged 65-74 years
rin
g
C
Patel H. Age Ageing (2013) 42:378
BG
S
Sp
• Up to 10% in hospital and over 30% in nursing
homes
Gariballa Clin Nutr (2013) 32:772
S
Sp
rin
g
C
on
f
er
en
2229 British birth cohort aged 60-64 years
Prevalence of low lean mass and weakness
FNIH definition:
1.1% m; 2.0% f
EWSGOP definition: 2.3% m; 6.4% f
FNIH criteria associated with higher odds of
slowness and difficulty walking
BG
•
•
•
•
•
ce
20
15
Prevalence of skeletal muscle deficit in early
old age
Cooper J Gerontol (2015) 604
15
ce
20
Consequences of sarcopenia
er
en
Higher current and future risk of
BG
S
Sp
rin
g
C
on
f
•Disability and poor mobility
•Falls and fractures
•Cardiovascular disease
•Reduced quality of life
•Hospital admission
•Increased mortality
Cooper R. Age Ageing (2011) 40:14
15
ce
20
Management of sarcopenia
er
en
• Exercise
rin
g
C
on
f
• Dietary
supplementation
BG
S
Sp
• Pharmacotherapy
15
20
er
en
ce
Leisure time physical activity
in adult life and grip strength
BG
S
Sp
rin
g
C
on
f
• 1645 adults had LTPA assessed at ages 36, 43, 53 and
60–64 and grip strength at 60–64
• Increased levels of LTPA across mid-life were
associated with stronger grip at age 60–64, in both men
and women, including adjustment for confounders.
• Data suggests that LTPA across adulthood may prevent
decline in grip strength in early old age.
Dodds R Age Ageing (2013) 42:794
S
BG
rin
g
Sp
on
f
C
ce
er
en
15
20
20
15
Exercise
on
f
er
en
ce
• Cochrane review of 121 randomised controlled trials
showed PRT can improve muscle strength and
performance in older people
rin
g
C
• Strength training may cause muscle hypertrophy and
beneficial changes in neuromuscular function
BG
S
Sp
• Other types of exercise interventions, involving gait,
balance, co-ordination and functional exercises, may
also be effective in reducing the risk and rate of falls as
well as improving balance in older people
Liu C. (2009) Cochrane Database systematic Reviews
S
BG
rin
g
Sp
on
f
C
ce
er
en
15
20
Diet
15
20
Dietary intake of protein
Low muscle mass is associated with lower protein intake
RDA protein 0.8g/kg/day
40% people aged >70 years do not meet this
PROT-AGE study group proposed intake of 1.25g/kg/day
for healthy older people with 25-30g protein/meal
• Older patients with acute/chronic disease require at least
1.2-1.5g/kg/day
• Whey protein preferable to casein protein: faster
digestion and absorption, greater leucine content
• Leucine found in chicken, fish, cottage cheese, lentils,
sesame, peanuts
BG
S
Sp
rin
g
C
on
f
er
en
ce
•
•
•
•
Bauer JAMDR (2013) 14:542
15
20
Protein supplementation
BG
S
Sp
rin
g
C
on
f
er
en
ce
• A Cochrane review found that the use of protein and
energy supplements in older people at risk of
malnutrition produced a small but consistent weight gain
and mortality appeared to be reduced in those who were
undernourished
• no evidence of functional benefit
• Limited evidence for supplementation with essential
amino acids
• Further work is needed to establish protein and specific
amino acid requirements to support optimal physical
function in older people.
15
20
Vitamin D supplementation
BG
S
Sp
rin
g
C
on
f
er
en
ce
• The vitamin D receptor (VDR) has been isolated from
skeletal muscle, and polymorphisms of the VDR have
been linked to differences in muscle strength
• fourfold increase in the risk of frailty has been described
in older men and women with low vitamin D status
• a meta-analysis indicated that vitamin D
supplementation (700–1000 IU/day) reduces risk of falls
in older people
• supplementation is not consistently linked to measurable
improvements in physical function, and its benefits
remain controversial
Robinson S. J Aging Res 2012:510801 [epub]
15
20
Diet quality
on
f
er
en
ce
• Higher antioxidant status is associated with increased
muscle function but trials of supplements are
inconclusive
rin
g
C
• High consumption of fish oils is associated with greater
strength and requires further research
BG
S
Sp
• “Healthy” diets, characterised by greater fruit and
vegetable consumption, wholemeal cereals, and oily fish,
have been shown to be associated with greater muscle
strength in older adults
Robinson S . JAGS (2008) 56:84
15
20
Diet and exercise
er
en
ce
• synergistic effects of protein feeding and exercise have
been described
rin
g
C
on
f
• initial benefits in older subjects have been blunted over
time
BG
S
Sp
• Remains unclear whether there are additional benefits of
protein/amino acid supplementation on the skeletal
muscle response to prolonged resistance exercise
training
Koopman R. Proc Nutr Soc (2011) 70:104
15
er
en
ce
20
Pharmacotherapy for sarcopenia
on
f
• Growth hormone increases muscle mass but
little evidence for improved function
Sp
rin
g
C
• Testosterone has adverse side effects eg
cardiovascular
BG
S
• Ace inhibitors may improve muscle function and
subject of current research
Decreased aerobic and sprinting
capacity even with rigorous exercise,
increased body fatness, insulin
resistance 204, decreased muscle
protein synthesis
Decreased physical activity,
Inflammation (increased cytokine
reduced androgen and growth
levels) , insulin resistance and type 2
factor levels , menopause,
diabetes , nutritional deficiencies
increased total body and visceral fat (protein, vitamin D, and other
, chronic disease, impaired appetite micronutrients) , reduced muscle
protein synthesis
regulation
Further reduction in physical
Fear of falling, low functional capacity ,
activity, bouts of enforced inactivity mild cognitive impairment, inflammation
due to illness, hospitalization
and increased muscle protein
depression, increased body fatness breakdown
C
rin
g
BG
70+
S
Sp
60–70
ce
Effects
Maintenance of VO2max with exercise
training, sprinting capacity is reduced
on
f
40–60
Potential causes
Decreased physical activity,
decreased type II muscle fiber size
and amount, maintenance of type I
fibers
Loss of motor units accelerates .
Decreased physical activity,
increased body fatness , decreased
androgens
er
en
Age
20–40
20
15
Sarcopenia Causes and effects by Age
20
15
A lifecourse approach to
sarcopenia
er
en
ce
• muscle mass and function in later life reflect the rate of
muscle loss and also the peak attained earlier in life
Sp
rin
g
C
on
f
• focus on the factors associated with peak muscle mass
and strength such as birth weight, early nutrition and
activity as well as the mechanisms underlying these
associations
BG
S
• Importantly, a lifecourse approach suggests that there is
potential for prevention and intervention at earlier stages
of life rather than just when sarcopenia has become
established
S
BG
rin
g
Sp
on
f
C
ce
er
en
15
20
15
ce
20
S
Sp
rin
g
C
on
f
er
en
Professor Avan Aihie Sayer
Professor Sian Robinson
Professor Cyrus Cooper
Dr Harnish Patel
Dr Richard Dodds
Dr Holly Syddall
Karen Jameson
Shirley Simmonds
BG
•
•
•
•
•
•
•
•