Sarcopenia – A Potential Target for Angiotensin-Converting Enzyme Inhibition?

Department of Medicine and Therapeutics, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.
Gerontology (Impact Factor: 3.06). 02/2006; 52(4):237-42. DOI: 10.1159/000093656
Source: PubMed


Society is ageing. There has been a steady increase in the number of people aged 65 years and over throughout the 20th century and this trend is predicted to continue worldwide. This has resulted in an increase in the incidence of sarcopenia, which is a loss of muscle mass and function with age. Maintenance of muscular function into old age is critical to sustaining normal daily activity and functional independence. Sarcopenia is associated with increased morbidity and mortality. Till now most efforts to counteract sarcopenia have met with limited success. We postulate that targeting the renin-angiotensin system through angiotensin-converting enzyme (ACE) inhibition could play a role in countering sarcopenia. ACE inhibitors could work by preventing mitochondrial decline and improving endothelial function and muscle metabolism. We describe the literature to support our hypothesis that sarcopenia may be a potential therapeutic target for ACE inhibitors.

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    • "If chronically lower ACE activity persists, caused by ACEIs, it prevents a decline of age-related muscle strength. ACE II genotype, potentially has lower ACE activity, which might affect change of age-related muscle function.12 So, the aim of this study was to investigate the difference of ACE activity level, according to the ACE genotypes, and the association between the ACE activity and muscular function of people aged 65, which puts forward the hypothesis that muscular function in the elderly, in connection with sarcopenia, is related to the ACE gene polymorphism. "
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    ABSTRACT: To investigate associations between angiotensin-converting enzyme (ACE) polymorphisms and muscle fatigability in 65-year-old Koreans. The study participants were 49 Koreans aged 65 years. ACE insertion/deletion (I/D) polymorphisms were determined by polymerase chain reaction and serum ACE activity, by spectrophotometry. Body mass index (BMI), body fat mass (BFM), and lean body mass (LBM) were determined. To evaluate muscle fatigability, dynamic Electromyography was used to measure maximum voluntary isometric contractions (MVICs) of ankle plantar flexor muscles. Patients were seated with their hips flexed at 90°, knees fully extended, and ankles at 0°. Continuous submaximal VICs (40% MVIC) were then performed, and contraction duration and EMG frequency changes during the initial 2 min were measured. A self-reported physical activity questionnaire was used to evaluate effects of ACE activity levels on muscle fatigability. Among the 49 volunteers, 15 showed II genotype; 22, ID genotype; and 12, DD genotype. Serum ACE activity levels were significantly higher in DD genotype subjects than in II genotype subjects (p<0.05). Furthermore, the duration of submaximal isometric contractions was longer in II and ID genotype subjects than in DD genotype subjects (p<0.05). Dynamic EMG showed significantly lower mean frequency changes in II genotype subjects than in DD genotype subjects (p<0.05). However, LBM, BFM, and BMI were independent of ACE genotypes. ACE II genotype subjects showed significantly higher resistant to muscle fatigue than that by DD genotype subjects. However, body composition and BMI showed no correlations with ACE I/D polymorphisms.
    Annals of Rehabilitation Medicine 08/2012; 36(4):433-46. DOI:10.5535/arm.2012.36.4.433
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    • "Statins may reduce physical disability by decreasing systemic inflammation as indicated by specific markers (e.g., C-reactive protein [CRP]).{Albert, 2001 #55}{Ridker, 1999 #104} ACE inhibitors may have direct effect on muscle in addition to reducing inflammation through reduction in angiotensin II.{Burton, #613} {Walston, 2006 #385}{Sumukadas, 2006 #350; Onder, 2007 #303}{Corsonello, #616} Indeed, one observational study showed that the use of ACE inhibitors in older adults with hypertension resulted in positive effects on mobility limitation as measured by gait speed. {Onder, 2002 #2}. "
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    ABSTRACT: To evaluate whether the use of angiotensin-converting enzyme (ACE) inhibitors and statins is associated with a lower risk of incident mobility limitation in older community dwelling adults. Longitudinal cohort study. Health, Aging and Body Composition (Health ABC) study. Three thousand fifty-five participants who were well functioning at baseline (no mobility limitations). Summated standardized daily doses (low, medium, high) and duration of ACE inhibitor and statin use were computed. Mobility limitation (two consecutive self-reports of having any difficulty walking one-quarter of a mile or climbing 10 steps without resting) was assessed every 6 months after baseline. Multivariable Cox proportional hazards analyses were conducted, adjusting for demographics, health status, and health behaviors. At baseline, 15.2% used ACE inhibitors and 12.9% used statins; use of both was greater than 25% by Year 6. Over 6.5 years of follow-up, 49.8% had developed mobility limitation. In separate multivariable models, neither ACE inhibitor (multivariate hazard ratio (HR) = 0.95, 95% confidence interval (CI) = 0.82-1.09) nor statin use (multivariate HR = 1.02, 95% CI = 0.87-1.17) was associated with lower risk of mobility limitation. Similar findings were seen in analyses examining dose-response and duration-response relationships and a sensitivity analysis restricted to those with hypertension. ACE inhibitors and statins widely prescribed to treat hypertension and hypercholesterolemia, respectively, do not lower risk of mobility limitation, an important indicator of quality of life.
    Journal of the American Geriatrics Society 11/2011; 59(12):2226-32. DOI:10.1111/j.1532-5415.2011.03721.x · 4.57 Impact Factor
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