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Epidemiology of sarcopenia and insight into possible therapeutic targets

Nature Reviews Rheumatology volume 13, pages 340–347 (2017)Cite this article

Subjects

Key Points

  • Sarcopenia, the age-related loss of muscle mass and function, is associated with considerable morbidity and health care costs

  • Approaches to defining sarcopenia remain controversial, although several groups have proposed ways of defining the condition

  • Moderate-quality evidence suggests that exercise interventions improve muscle strength and physical performance in patients with sarcopenia, whereas the benefits of nutritional interventions are more equivocal

  • Most pharmacological agents for sarcopenia investigated to date are hormonal (testosterone and selective androgen receptor modulators) although therapies targeting myostatin signalling are emerging as new developments

Abstract

Musculoskeletal ageing is a major public health concern owing to demographic shifts in the population. Sarcopenia, generally defined as the age-related loss of muscle mass and function, is associated with considerable risk of falls, loss of independence in older adults and hospitalization with poorer health outcomes. This condition is therefore associated with increased morbidity and health care costs. As with bone mass, muscle mass and strength increase during late adolescence and early adulthood, but begin to decline substantially from ∼50 years of age. Sarcopenia is characterized by many features, which include loss of muscle mass, altered muscle composition, infiltration with fat and fibrous tissue and alterations in innervation. A better understanding of these factors might help us to develop strategies that target these effects. To date, however, methodological challenges and controversies regarding how best to define the condition, in addition to uncertainty about what outcome measures to consider, have delayed research into possible therapeutic options. Most pharmacological agents investigated to date are hormonal, although new developments have seen the emergence of agents that target myostatin signalling to increase muscle mass. In this review we consider the current approaching for defining sarcopenia and discuss its epidemiology, pathogenesis, and potential therapeutic opportunities.

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Figure 1: Grip strength across the lifecourse.
Figure 2: Risk factors for sarcopenia.

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References

  1. United Nations, Department of Economic and Social Affairs, Population Division. World Population Ageing 2013 (United Nations, 2013).

  2. Dawson, A. & Dennison, E. Measuring the musculoskeletal aging phenotype. Maturitas 93, 13–17 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  3. Cooper, C. et al. Frailty and sarcopenia: definitions and outcome parameters. Osteoporos. Int. 23, 1839–1848 (2012).

    Article  CAS  PubMed  Google Scholar 

  4. Cooper, C. et al. Tools in the assessment of sarcopenia. Calcif. Tissue Int. 93, 201–210 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Dodds, R. & Aihie Sayer, A. Sarcopenia and frailty: new challenges for clinical practice. Clin. Med. 15 (Suppl. 6), s88–s91 (2015).

    Article  Google Scholar 

  6. McGregor, R., Cameron-Smith, D. & Poppitt, S. It is not just muscle mass: a review of muscle quality, composition and metabolism during ageing as determinants of muscle function and mobility in later life. Longev. Healthspan 3, 9 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  7. Lang, T. et al. Sarcopenia: etiology, clinical consequences, intervention and assessment. Osteoporos. Int. 21, 543–559 (2010).

    Article  CAS  PubMed  Google Scholar 

  8. Studenski, S. A. et al. The FNIH Sarcopenia project: rationale, study description, conference recommendations and final estimates. J. Gerontol. A Biol. Sci. Med. Sci. 69, 547–558 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  9. Landi, F. et al. Impact of physical function impairment and multimorbidity on mortality among community-living older persons with sarcopenia: results from the ilSIRENTE prospective cohort study. BMJ Open 6, e008281 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  10. Fried, C. M. et al. Frailty in older adults: evidence for a phenotype. J. Gerontol. A Biol. Sci. Med. Sci. 56, M146–M156 (2001).

    Article  CAS  PubMed  Google Scholar 

  11. Calvani, R. et al. Biomarkers for physical frailty and sarcopenia: state of the science and future developments. J. Cachexia Sarcopenia Muscle 6, 278–286 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  12. Dodds, R. M. et al. Grip strength across the life course: normative data from twelve British studies. PLoS ONE 9, e113637 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  13. Sayer, A. A. et al. The developmental origins of sarcopenia. J. Nutr. Health Aging 12, 427–432 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Chen, L. K. et al. Sarcopenia in Asia: consensus report of the Asian Working Group for Sarcopenia. J. Am. Med. Dir. Assoc. 15, 95–101 (2014).

    Article  PubMed  Google Scholar 

  15. Dodds, R. M. et al. Prevalence and incidence of sarcopenia in the very old: findings from the Newcastle 85+ Study. J. Cachexia Sarcopenia Muscle 8, 229–237 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  16. Patel, H. P. et al. Prevalence of sarcopenia in community-dwelling older people in the UK using the European Working Group on Sarcopenia in Older People (EWGSOP) definition: findings from the Hertfordshire Cohort Study (HCS). Age Ageing 42, 378–384 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  17. Bortz, W. M. II. A conceptual framework of frailty: a review. J. Gerontol. A Biol. Sci. Med. Sci. 57, M283–M288 (2002).

    Article  PubMed  Google Scholar 

  18. Animoto, Y. et al. Association of sarcopenia with functional decline in community-dwelling elderly subjects in Japan. Geriatr. Gerontol. Int. 13, 958–963 (2013).

    Article  Google Scholar 

  19. Janssen, I., Baumgartner, R. N., Ross, R., Rosenberg, I. H. & Roubenoff, R. Skeletal muscle cutpoints associated with elevated physical disability risk in older men and women. Am. J. Epidemiol. 159, 413–421 (2004).

    Article  PubMed  Google Scholar 

  20. Hardy, S. E., Kang, Y., Studenski, S. A. & Degenholtz, H. B. Ability to walk ¼ mile predicts subsequent disability, mortality and healthcare costs. J. Gen. Intern. Med. 26, 130–135 (2011).

    Article  PubMed  Google Scholar 

  21. Tanimoto, Y. et al. Sarcopenia and falls in community-dwelling elderly subjects in Japan: defining sarcopenia according to criteria of the European Working Group on Sarcopenia in Older People. Arch. Gerontol. Geriatr. 59, 295–299 (2014).

    Article  PubMed  Google Scholar 

  22. Sheetz, K. H. et al. Cost of major surgery in the sarcopenic patients. J. Am. Coll. Surg. 217, 813–818 (2013).

    Article  PubMed  Google Scholar 

  23. Englesbe, M. J. et al. Sarcopenia and mortality after liver transplantation. J. Am. Coll. Surg. 211, 271–278 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  24. Tan, B. H., Birdsell, L. A., Martin, L., Baracos, V. E. & Fearon, K. C. Sarcopenia is an overweight or obsese patient is an adverse prognostic factor in pancreatic cancer. Clin. Cancer Res. 15, 6973–6979 (2009).

    Article  CAS  PubMed  Google Scholar 

  25. Janssen, I., Shepard, D. S., Katzmarzyk, P. T. & Roubenoff, R. The healthcare costs of sarcopenia in the United States. J. Am. Geriatr. Soc. 52, 80–85 (2004).

    Article  PubMed  Google Scholar 

  26. Beaudart, C. et al. Development of a self-administered quality of life questionnaire for sarcopenia in elderly subjects: the SarQol. Age Ageing 44, 960–966 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  27. Brioche, T., Pagano, A. F., Py, G. & Chopard, A. Muscle wasting and aging: experimental models, fatty infiltrations and prevention. Mol. Aspects Med. 50, 56–87 (2016).

    CAS  Google Scholar 

  28. Jackson, M. J. Reactive oxygen species in sarcopenia: should we focus on excessive oxidative damage or defective redox signalling? Mol. Aspects Med. 50, 33–40 (2016).

    CAS  Google Scholar 

  29. Sousa-Victor, P. & Munoz-Canaves, P. Regenerative decline of stem cells in sarcopenia. Mol. Aspects Med. 50, 109–117 (2016).

    CAS  Google Scholar 

  30. Marzetti, E. et al. Skeletal muscle apoptotic signaling predicts thigh muscle volume and gait speed in community-dwelling older persons: an exploratory study. PLoS ONE 7, e32829 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Sayer, A. A. et al. New horizons in the pathogenesis, diagnosis and management of sarcopenia. Age Ageing 42, 145–150 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  32. Piasecki, M., Ireland, A., Jones, D. A. & McPhee, J. S. Age-dependent motor unit remodelling in human limb muscles. Biogerontology 17, 485–496 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  33. Blau, H. M., Cosgrove, B. D. & Ho, A. T. V. The central role of muscle stem cells in regenerative failure with aging. Nat. Med. 21, 854–862 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Franceschi, C. et al. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann. NY Acad. Sci. 908, 244–254 (2000).

    Article  CAS  PubMed  Google Scholar 

  35. De Martinis, M., Franceschi, C., Monti, D. & Ginaldi, L. Inflamm-ageing and lifelong antigenic load as major determinants of ageing rate and longevity. FEBS Lett. 579, 2035–2039 (2005).

    Article  CAS  PubMed  Google Scholar 

  36. Cannizzo, E. S., Clement, C. C., Sahu, R., Follo, C. & Santambrogio, L. Oxidative stress, inflamm-aging and immunosenescence. J. Proteomics 74, 2313–2323 (2011).

    Article  CAS  PubMed  Google Scholar 

  37. Ferrucci, L. et al. Serum IL-6 level and the development of disability in older persons. J. Am. Geriatr. Soc. 47, 639–646 (1999).

    Article  CAS  PubMed  Google Scholar 

  38. Wilson, D., Jackson, T., Sapey, E. & Lord, J. M. Frailty and sarcopenia: the potential role of an aged immune system. Ageing Res. Rev. 36, 1–10 (2017).

    Article  PubMed  Google Scholar 

  39. Cauley, J. A. An overview of sarcopenic obesity. J. Clin. Densitom. 18, 499–505 (2015).

    Article  PubMed  Google Scholar 

  40. Kalinkovich, A. & Livshits, G. Sarcopenic obesity or obese sarcopenia: a cross talk between age-associated adipose tissue and skeletal muscle inflammation as a main mechanism of the pathogenesis. Ageing Res. Rev. 35, 200–221 (2016).

    Article  PubMed  Google Scholar 

  41. Villareal, D. T., Banks, M., Siener, C., Sinacore, D. R. & Klein, S. Physical frailty and body composition in obese elderly men and women. Obes. Res. 12, 913–920 (2004).

    Article  PubMed  Google Scholar 

  42. Szulc, P., Duboeuf, F., Marchand, F. & Delmas, P. Hormonal and lifestyle determinants of appendicular skeletal muscle mass in men: the MINOS study. Am. J. Clin. Nutr. 80, 496–503 (2004).

    Article  CAS  PubMed  Google Scholar 

  43. Kortebein, P. et al. Effect of 10 days of bed rest on skeletal muscle in healthy older adults. JAMA 297, 1772–1774 (2007).

    Article  CAS  PubMed  Google Scholar 

  44. Zampieri, S. et al. Lifelong physical exercise delays age associated skeletal muscle decline. J. Gerontol. A Biol. Sci. Med. Sci. 70, 163–173 (2014).

    Article  PubMed  Google Scholar 

  45. Hinrichs, T. et al. Inverse effects of midlife occupational and leisure time physical activity on mobility limitation in old age — a 28-year prospective follow-up study. J. Am. Geriatr. Soc. 62, 812–820 (2014).

    Article  PubMed  Google Scholar 

  46. Arnold, P. & Boutmans, I. The influence of strength training on muscle activation in elderly persons: a systematic review and meta-analysis. Exp. Gerontol. 58, 58–68 (2014).

    Article  PubMed  Google Scholar 

  47. Law, T. D., Clark, L. A. & Clark, B. C. Resistance exercise to prevent and manage sarcopenia and dynapenia. Annu. Rev. Gerontol. Geriatr. 36, 205–228 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  48. Renoud, A., Ecochard, R., Marchand, F., Chapurlat, R. & Szulc, P. Predictive parameters of accelerated muscle loss in men – MINOS study. Am. J. Med. 127, 554–561 (2014).

    Article  PubMed  Google Scholar 

  49. Curtis, E., Litwic, A., Cooper, C. & Dennison, E. Determinants of muscle and bone aging. J. Cell. Physiol. 230, 2618–2625 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Song, D. S. et al. Heavy alcohol consumption with alcoholic liver disease accelerates sarcopenia in elderly Korean males: the Korean National Health and Nutrition Examination Survey 2008–2010. PLoS ONE 11, e0163222 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  51. Steffl, M., Bohannon, R. W., Petr, M., Kohlikova, E. & Holmerova, I. Alcohol consumption as a risk factor for sarcopenia — a meta-analysis. BMC Geriatr. 16, 99 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  52. Rolland, Y. et al. Sarcopenia: its assessment, etiology, pathogenesis, consequences and future perspectives. J. Nutr. Health Aging 12, 433–450 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Rizzoli, R. et al. The role of dietary protein and vitamin D in maintaining musculoskeletal health in postmenopausal women: a consensus statement from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis. Maturitas 79, 122–132 (2014).

    Article  CAS  PubMed  Google Scholar 

  54. Short, K. R. et al. Age and aerobic exercise training effects on whole muscle body and muscle protein metabolism. Am. J. Physiol. Endocrinol. Metab. 286, E92–E101 (2004).

    Article  CAS  PubMed  Google Scholar 

  55. Volpi, E., Sheffield-Moore, M., Rasmussen, B. B. & Wolfe, R. R. Basal muscle amino acid kinetics and protein synthesis in healthy young and older men. JAMA 286, 1206–1212 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Rennie, M. J. et al. Muscle protein synthesis measured by stable isotope techniques in man: the effects of feeding and fasting. Clin. Sci. (Lond.) 63, 519–523 (1982).

    Article  CAS  Google Scholar 

  57. Pennings, B. et al. Amino acid absorption and subsequent muscle protein accretion following graded intakes of whey protein in elderly men. Am. J. Physiol. Endocrinol. Metab. 302, E992–E999 (2012).

    Article  CAS  PubMed  Google Scholar 

  58. Denison, H. J., Cooper, C., Sayer, A. A. & Robinson, S. M. Prevention and optimal management of sarcopenia: a review of controlled exercise and nutrition interventions to improve muscle outcomes in older people. Clin. Interv. Aging 10, 859–869 (2015).

    PubMed  PubMed Central  Google Scholar 

  59. Bischoff-Ferrari, H. A. Optimal serum 25-hydroxyvitamin D levels for multiple health outcomes. Adv. Exp. Med. Biol. 810, 500–525 (2014).

    PubMed  Google Scholar 

  60. Visser, M., Deeg, D. J. & Lips, P. Low vitamin D and high parathyroid hormone levels as determinants of loss of muscle strength and muscle mass (sarcopenia): the Longitudinal Aging Study Amsterdam. J. Clin. Endocrinol. Metab. 88, 5766–5772 (2003).

    Article  CAS  PubMed  Google Scholar 

  61. Cruz-Jentoft, A. J. et al. Prevalence of and interventions for sarcopenia in ageing adults: a systematic review. Report of the International Sarcopenia Initiative (EWGSOP and IWGS). Age Ageing 43, 748–759 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  62. Reginster, J.-Y. et al. Recommendations for the conduct of clinical trials for drugs to treat or prevent sarcopenia. Aging Clin. Exp. Res. 28, 47–58 (2016).

    Article  PubMed  Google Scholar 

  63. Atkinson, R. A. et al. Effects of testosterone on skeletal muscle architecture in intermediate-frail and frail elderly men. J. Gerontol. 65, 1215–1219 (2010).

    Article  Google Scholar 

  64. Dalton, J. T. et al. The selective androgen receptor modulator GTx-024 (enobosarm) improves lean body mass and physical function in healthy elderly men and postmenopausal women: results of a double-blind, placebo-controlled phase II trial. J. Cachexia Sarcopenia Muscle 2, 153–161 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  65. Papanicolaou, D. A. et al. Phase IIA randomised placebo-controlled clinical trial to study the efficacy and safety of the selective androgen receptor modulator (SARM), MK-0773 in female participants with sarcopenia. J. Nutr. Health Aging 17, 533–543 (2013).

    Article  CAS  PubMed  Google Scholar 

  66. Becker, C. et al. Myostatin antibody (LY2495655) in older weak fallers: a proof of concept, randomised phase II trial. Lancet Diabetes Endocrinol. 3, 948–957 (2015).

    Article  CAS  PubMed  Google Scholar 

  67. Amato, A. A. et al. Treatment of sporadic inclusion body myositis with bimagrumab. Neurology 83, 2239–2246 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Bechir, N. et al. Mitochondrial impairment induced by postnatal ActRIIB blockade does not alter function and energy status in exercising mouse glycolytic muscle in vivo. Am. J. Physiol. Endocrinol. Metab. 310, E539–E549 (2015).

    Article  Google Scholar 

  69. Marzetti, E. et al. Mitochondrial dysfuntion and sarcopenia of aging: from signalling pathways to clinical trials. Int. J. Biochem. Cell Biol. 45, 2288–2301 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Beaudart, C. et al. Sarcopenia in daily practice: assessment and management. BMC Geriatr. 16, 170 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  71. Martone, A. M. et al. Treating sarcopenia in older and oldest old. Curr. Pharm. Des. 21, 1715–1722 (2015).

    Article  CAS  PubMed  Google Scholar 

  72. Landi, F. et al. Sarcopenia as the biological substrate of physical frailty. Curr. Geriatr. Med. 31, 367–374 (2015).

    Article  Google Scholar 

  73. Muscaritoli, M. et al. Consensus definition of sarcopenia, cachexia and pre-cachexia: joint document elaborated by Special Interest Groups (SIG) “cachexia-anorexia in chronic wasting diseases” and “nutrition in geriatrics”. Clin. Nutr. 29, 154–159 (2010).

    Article  CAS  PubMed  Google Scholar 

  74. Cruz-Jentoft, A. J. et al. Sarcopenia: European consensus on definition and diagnosis: report of the European Working Group on Sarcopenia in Older People. Age Ageing 39, 412–423 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  75. Fielding, R. A. et al. International Working Group on Sarcopenia Sarcopenia: an undiagnosed condition in older adults. Current consensus definition: prevalence, etiology, and consequences. J. Am. Med. Dir. Assoc. 12, 249–256 (2011).

    Article  PubMed  Google Scholar 

  76. Morley, J. E. et al. Sarcopenia with limited mobility: an international consensus. J. Am. Med. Dir. Assoc. 12, 403–409 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

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Author information

Authors and Affiliations

  1. MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK

    Elaine M. Dennison, Avan A. Sayer & Cyrus Cooper

  2. School of Biological Sciences, Victoria University of Wellington, Kelburn Parade, Wellington, 6012, New Zealand

    Elaine M. Dennison

  3. NIHR Collaboration for Leadership in Applied Health Research and Care Wessex, University of Southampton, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK

    Avan A. Sayer

  4. Institute of Neuroscience, Henry Wellcome Building, The Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne, NE1 7RU, UK

    Avan A. Sayer

  5. NIHR Newcastle Biomedical Research Centre, Newcastle University, Campus for Ageing and Vitality, Westgate Road, Newcastle upon Tyne, NE4 5PL, UK

    Avan A. Sayer

  6. Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital, Freeman Road, High Heaton, Newcastle upon Tyne, NE7 7DN, UK

    Avan A. Sayer

  7. Nuffield Department of Orthopaedics, NIHR Musculoskeletal Biomedical Research Unit, Rheumatology and Musculoskeletal Sciences, University of Oxford, Windmill Road, Oxford, OX3 7LD, UK

    Cyrus Cooper

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E.M.D. researched data for the article and wrote the manuscript. A.A.S. and C.C. both contributed substantially to the discussion of the content, and reviewed and edited the manuscript before submission.

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Correspondence to Elaine M. Dennison.

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Competing interests

C.C. declares that he has received consultancy fees and honoraria from Alliance for Better Bone Health, Amgen, GSK, Lilly, Medtronic, Merck, Novartis, Pfizer, Roche, Servier, Takeda and UCB. E.M.D. declares that she has received speaker's fees from Lilly. A.S. declares no competing interests.

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Dennison, E., Sayer, A. & Cooper, C. Epidemiology of sarcopenia and insight into possible therapeutic targets. Nat Rev Rheumatol 13, 340–347 (2017). https://doi.org/10.1038/nrrheum.2017.60

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