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 The Author 2008. Published by Oxford University Press on behalf of the British Geriatrics Society.
All rights reserved. For Permissions, please email: [email protected] Published electronically 30 May 2008 ACE inhibitors for sarcopenia—as good as
exercise training?
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 [3]. 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 [4].
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 [5]. 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 [6].
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 [7]; 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 [8].
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 [9]. 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 [10]. 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 [11], 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 [12], and vitamin D [13], 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 [14]. Patients were all aged 65 years and over, and were excluded if they had concurrent heart failure or LV systolic dysfunction. At baseline, patients 1. 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.
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group received placebo. The intervention group achieved a 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 4. 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 5. 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 6. Sayer AA, Syddall HE, Dennison EM et al. Grip strength
six months of exercise training [15], and the intervention and the metabolic syndrome: findings from the Hertfordshire was well tolerated with nonsignificantly fewer falls in the Cohort Study. QJM 2007; 100: 707–13.
treatment group.
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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.
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