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Age and Ageing
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Published electronically 30 May 2008
ACE inhibitors for sarcopenia—as good as
Sarcopenia is a major health problem for older people.
together with preferential loss of type II (fast twitch)
Progressive impairment in muscle strength and loss of
fibres and changes in calcium handling by the sarcoplasmic
muscle mass are key contributors to falls, fractures and
reticulum . These changes lead to reductions in maximal
reduced physical function, is a key risk factor for death, and
muscle strength, affecting predominantly explosive power
for the need for assistance with activities of daily living [1, 2].
but also leading to increased fatigability.
Finding effective ways to prevent and reverse sarcopenia,
The biological mechanisms underlying the pathophysio-
therefore, has great importance as a way of attempting to
logical changes of sarcopenia are still not well understood,
reduce falls and immobility, avoid institutionalisation and
but basic science and epidemiological studies have given
enhance healthy ageing.
us important insights in the last few years. Satellite cells
No consensus threshold for diagnosing sarcopenia has
in muscle, which usually provide the substrate for mus-
yet been arrived at, but the pathophysiological hallmarks
cle regeneration, are lower in number in older people .
of the condition are becoming better defined. Reduced
Chronic inflammation is linked to sarcopenia, with proin-
cross-sectional muscle area, fibre loss and reduced muscle
flammatory cytokines, including IL-6 and TNF alpha,
quality all play a part; mitochondrial dysfunction occurs
thought to have deleterious actions on muscle . Hormonal
changes are also thought to play a role, and there are emerging
are also known to improve endothelial function, muscle
links between the metabolic syndrome and sarcopenia .
glucose uptake, increase potassium levels and modulate
Finally, a number of lines of epidemiological evidence now
other hormonal systems including IGF-1, all of which could
link the renin-angiotensin-aldosterone (RAAS) system to
contribute to improved skeletal muscle function. Finally,
skeletal muscle function. Individuals with the II genotype of
ACE inhibitors could of course be mediating a direct effect
the ACE gene have greater endurance and greater skeletal
on skeletal muscle structure and function; they are known to
muscle trainability in some studies ; hypertensive patients
have trophic effects on myocardial tissue.
taking ACE inhibitors have greater cross-sectional muscle
What does this mean for the treatment of older people?
mass and a slower decline in walking speed than those taking
Firstly, it should give us reassurance that older people treated
other antihypertensives in epidemiological studies .
with ACE inhibitors for other cardiovascular conditions are
What works in sarcopenia? The best evidence to date
very unlikely to suffer from worsening physical function as a
is exercise. Both endurance and resistance exercise improve
result of therapy. More excitingly, it promises to reinvigorate
skeletal muscle function and cross-sectional area, even in very
attempts to find pharmacological approaches to the difficult
old patients . These benefits are not simply abstract but
problem of sarcopenia. More work is now needed to
can translate into an enhanced ability to perform activities
understand the precise mechanisms underlying the observed
of daily living . However, as many older people are
clinical effect, to test how best to combine interventions
unwilling or simply unable to engage in exercise training
such as exercise and ACE inhibitors for treating sarcopenia,
other avenues need to be explored. The appealing prospect
and to explore whether other interventions suggested by
of a pill which might confer improved exercise capacity has
observational work and basic science might have beneficial
led to a number of pharmacological interventions being
effects on this problem that afflicts vast numbers of older
evaluated. These include testosterone , which shows
moderate effects on muscle strength in older men, growthhormone, which is expensive, shows only modest effects and
ILES D. WITHAM , DEEPA SUMUKADAS,
has problematic side-effects , and vitamin D , which
MARION E. T. MCMURDO
has shown improvements in muscle function in some, but
Section of Ageing and Health, University of Dundee,
not all studies.
Ninewells Hospital and Medical School, Dundee DD1 9SY, UK
Following on from recent observational data suggesting
a beneficial effect of ACE inhibitors, we recently reported
∗To whom correspondence should be addressed
results from a randomised controlled trial of ACE inhibitorson physical function involving 130 older patients withimpairment of daily activities . Patients were all aged
65 years and over, and were excluded if they had concurrent
heart failure or LV systolic dysfunction. At baseline, patients
Rantanen T, Avlund K, Suominen H et al
. Muscle strength as
had a wide range of comorbid conditions and had significant
a predictor of onset of ADL dependence in people aged 75
impairment of physical function —the baseline six-minute
years. Aging Clin Exp Res 2002; 14: 10–5.
walk distance was only 300 metres and the median baseline
Laukkanen P, Heikkinen E, Kauppinen M. Muscle strength
and mobility as predictors of survival in 75-84-year-old people.
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potential target for Angiotensin-converting enzyme inhibition?
31 m improvement in the six-minute walk distance compared
Gerontology 2006; 52: 237–42.
to placebo at 20 weeks (p = 0.003); quality of life as measured
Kadi F, Charifi N, Denis C et al
. Satellite cells and myonuclei
by the EuroQol 5D tool also improved by a clinically
in young and elderly women and men. Muscle Nerve 2004; 29:
significant 0.09 points relative to placebo (p = 0.046), and
there was a nonsignificant improvement in the timed-up
Roubenoff R. Physical activity, inflammation, and muscle loss.
and go time (1.3 seconds, p = 0.08). The improvement in
Nutr Rev 2007; 65: S208–12.
exercise capacity recorded is equivalent to that reported after
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What remains less clear from these results is the
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Onder G, Penninx BW, Balkrishnan R et al
have effects on cardiac function, and it is possible that
between use of angiotensin-converting enzyme inhibitors and
they improved cardiac output, and hence, muscle blood
muscle strength and physical function in older women: an
supply —many patients in this study had cardiovascular
observational study. Lancet 2002; 359: 926–30.
disease, and a high proportion of older people display
Fiatarone MA, Marks EC, Ryan ND et al
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Lack of Association of the S769N Mutation in Plasmodium falciparumSERCA (PfATP6) with Resistance to Artemisinins Long Cui,a Zenglei Wang,a Hongying Jiang,b Daniel Parker,a Haiyan Wang,c Xin-Zhuan Su,b and Liwang Cuia Department of Entomology, The Pennsylvania State University, University Park, Pennsylvania, USAa; Laboratory of Malaria and Vector Research, National Institute of Allergy
Managing Ringworm in the Sport of Judo Report from Sports Medicine and Science Committee Introduction Due to the close contact inherent in the sport of judo, athletes are more susceptible to skin disorder transmissions. Many types of skin disorders exist and we will not be able to cover them all in this report. The focus will be on one particular skin condition affecting many judo athletes over the past 3 years… "Ringworm".