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Sarcopenia (from Greek σάρξ sarx, "flesh" and πενία penia, "poverty") is the degenerative loss of skeletal muscle mass (0.5–1% loss per year after the age of 50), quality, and strength associated with aging. Sarcopenia is a component of the frailty syndrome. It is often a component of cachexia. It can also exist independently of cachexia; whereas cachexia includes malaise and is secondary to an underlying pathosis (such as cancer), sarcopenia may occur in healthy people and does not necessarily include malaise.


Sarcopenia is not a disease or a syndrome, and it is not always even a medical sign, because the degree to which it is normal (physiologic) versus abnormal (pathologic) is not determined. As of 2009 there is no generally accepted definition of sarcopenia in the medical literature.[1]

The European Working Group on Sarcopenia in Older People (EWGSOP) developed a clinical definition and consensus diagnostic criteria for age-related sarcopenia, using the presence of both low muscle mass and low muscle function (strength or performance).[2]

Signs and symptoms[edit]

Sarcopenia is characterized first by a muscle atrophy (a decrease in the size of the muscle), along with a reduction in muscle tissue quality, characterized by such factors as replacement of muscle fibres with fat, an increase in fibrosis, changes in muscle metabolism, oxidative stress, and degeneration of the neuromuscular junction and leading to progressive loss of muscle function and frailty.[3] Sarcopenia is determined by two factors: initial amount of muscle mass and rate at which aging decreases muscle mass. Due to the loss of independence associated with loss of muscle strength, the threshold at which muscle wasting becomes a disease is different pathologically from person to person.[4]

Simple circumference measurement does not provide enough data to determine whether or not an individual is suffering from severe sarcopenia. Sarcopenia is also marked by a decrease in the circumference of distinct types of muscle fibers. Skeletal muscle has different fiber-types, which are characterized by expression of distinct myosin variants. During sarcopenia, there is a decrease in "type 2" fiber circumference (Type II), with little to no decrease in "type I" fiber circumference (Type I), and deinervated type 2 fibers are often converted to type 1 fibers by reinnervation by slow type 1 fiber motor nerves.[5]


Satellite cells are small mononuclear cells that abut the muscle fiber. Satellite cells are normally activated upon injury or exercise. These cells then differentiate and fuse into the muscle fiber, helping to maintain its function. One theory is that sarcopenia is in part caused by a failure in satellite cell activation.[3]

Extreme muscle loss is often a result of both diminishing anabolic signals, such as growth hormone and testosterone, and promotion of catabolic signals, such as pro-inflammatory cytokines.[3]

Oxidized proteins increase in skeletal muscle with age and leads to a build up of lipofuscin and cross-linked proteins that are normally removed via the proteolysis system. These proteins compile in the skeletal muscle tissue, but are dysfunctional. This leads to an accumulation of non-contractile material in the skeletal muscle. This helps explain why muscle strength decreases severely, as well as muscle mass, in sarcopenia. [6]

One group has suggested that the evolutionary basis for the failure of the body to maintain muscle mass and function with age is that the genes governing these traits were selected in a Late Paleolithic environment in which there was a very high level of obligatory muscular effort, and that these genetic parameters are therefore ill-matched to a modern lifestyle characterized by high levels of lifelong sedentary behavior.[7]


A working definition for diagnosis was proposed in 1998 by Baumgartner et al which uses a measure of lean body mass as determined by dual energy X-ray absorptiometry (DEXA) compared to a normal reference population. His working definition uses a cut point of 2 standard deviations below the mean of lean mass for gender specific healthy young adults.[8]

This methodology shows it is predictive of negative outcomes and it is also a method familiar to most clinicians. This latter point is especially true for those that treat the geriatric population, given its similarity to the 1996 World Health Organization (WHO) methodology for definitive diagnosis of osteoporosis, which also uses DEXA, but uses a measure of lean mass rather than bone mineral density (BMD). DEXA is widely used already in clinical settings in developed countries to identify and monitor severity of osteoporosis. And the degree of sarcopenia can be measured using DEXA in patients being evaluated for osteoporosis, at the same time with the same scan, with no added cost or radiation exposure to the patient.[medical citation needed]

Since Baumgartner’s working definition first appeared, some consensus groups have refined the definition, including the recent joint effort of the European Society on Clinician Nutrition and Metabolism (ESPEN) Special Interest Groups (SIG) on geriatric nutrition and on cachexia-anorexia in chronic wasting diseases. Their consensus definition is:[9]

1) A low muscle mass, >2 standard deviations below that mean measured in young adults (aged 18–39 years in the 3rd NHANES population) of the same sex and ethnic background, and
2) Low gait speed (e.g. a walking speed below 0.8 m/s in the 4-m walking test).[9]



Lack of exercise is thought to be a significant risk factor for sarcopenia.[10] Even highly trained athletes experience its effects; master-class athletes who continue to train and compete throughout their adult lives exhibit a progressive loss of muscle mass and strength, and records in speed and strength events decline progressively after age 30.[3][11]

Master-class athletes maintain a high level of fitness throughout their lifespan. Even among master athletes, performance of marathon runners and weight lifters declines after approximately 40 years of age, with peak levels of performance decreased by approximately 50% by 80 years of age.[12] However a gradual loss of muscle fibres begins only at approximately 50 years of age.[12]

Exercise is of interest in treatment of sarcopenia; evidence indicates increased ability and capacity of skeletal muscle to synthesize proteins in response to short-term resistance exercise.[13]


Currently, no agents are approved for treatment of sarcopenia. DHEA and human growth hormone have been shown to have little to no effect in this setting. Growth hormone increases muscle protein synthesis and increases muscle mass, but does not lead to gains in strength and function in most studies.[14] This, and the similar lack of efficacy of its effector insulin-like growth factor 1 (IGF-1), may be due to local resistance to IGF-1 in aging muscle, resulting from inflammation and other age changes.[14]

Testosterone or other anabolic steroids have also been investigated for treatment of sarcopenia, and seem to have some positive effects on muscle strength and mass, but cause several side effects and raise concerns of prostate cancer in men and virilization in women.[14][15] Additionally, recent studies suggest testosterone treatments may induce adverse cardiovascular events.[16][17][18] Other approved medications under investigation as possible treatments for sarcopenia include ghrelin, vitamin D, angiotensin converting enzyme inhibitors, and eicosapentaenoic acid.[14][15]

New therapies in clinical development include myostatin and the selective androgen receptor modulators (SARMs).[19] Nonsteriodal SARMs are of particular interest, given they exhibit significant selectivity between the anabolic effects of testosterone on muscle, but with little to no evidence of androgenic effects (such as prostate stimulation in men).[19]

MT-102, the first-in-class anabolic catabolic transforming agent (ACTA), has recently been tested in a Phase-II clinical study for treating cachexia in late-stage cancer patients. The study data show significant increases in body weight in patients treated with 10 mg of MT-102 twice daily over the study period of 16 weeks compared to significant decrease in body weight in patients receiving placebo treatment.[20] In preclinical models, MT-102 has also shown benefits in reversing sarcopenia in elderly animals.[21] Future clinical studies will investigate sarcopenia as potential second indication for MT-102.

Novartis proposes the use of a new molecule BYM338 Bimagrumab for treatment of sarcopenia and plans to make a FDA submisson in 2019. [22]

Society and culture[edit]

Due to the lessened physical activity and increased longevity of industrialized populations, sarcopenia is emerging as a major health concern. Sarcopenia may progress to the extent that an older person may lose his or her ability to live independently. Furthermore, sarcopenia is an important independent predictor of disability in population-based studies, linked to poor balance, gait speed, falls, and fractures. Sarcopenia can be thought of as a muscular analog of osteoporosis, which is loss of bone, also caused by inactivity and counteracted by exercise. The combination of osteoporosis and sarcopenia results in the significant frailty often seen in the elderly population.

Research directions[edit]

Many opportunities remain for further refinement of reference populations by ethnic groups, and to further correlate the degrees of severity of sarcopenia to overt declines in functional performance (preferably using verified functional tests), as well as incidence of hospitalization admissions, morbidity, and mortality. The body of research points toward severe sarcopenia being predictive of negative outcomes, similar to those already shown to exist with frailty syndrome, as defined by the criteria set forth in 2001 by Fried et al.[23]

See also[edit]


  1. ^ Visser M (October 2009). "Towards a definition of sarcopenia--results from epidemiologic studies" (PDF). J Nutr Health Aging (Review) 13 (8): 713–6. doi:10.1007/s12603-009-0202-y. PMID 19657555. 
  2. ^ Cruz-Jentoft AJ, Baeyens JP, Bauer JM, et al. (July 2010). "Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People". Age Ageing 39 (4): 412–23. doi:10.1093/ageing/afq034. PMC 2886201. PMID 20392703. 
  3. ^ a b c d Ryall JG, Schertzer JD, Lynch GS (August 2008). "Cellular and molecular mechanisms underlying age-related skeletal muscle wasting and weakness". Biogerontology (Review) 9 (4): 213–28. doi:10.1007/s10522-008-9131-0. PMID 18299960. 
  4. ^ Marcell TJ (October 2003). "Sarcopenia: causes, consequences, and preventions". J. Gerontol. A Biol. Sci. Med. Sci. (Review) 58 (10): M911–6. doi:10.1093/gerona/58.10.m911. PMID 14570858. 
  5. ^ Doherty TJ (2003). "Invited review: Aging and sarcopenia". J Appl Physiol (Review) 95 (4): 1717–27. doi:10.1152/japplphysiol.00347.2003. PMID 12970377. 
  6. ^ Marcell, Taylor. 2003. Sarcopenia: Causes, Consequences, and Preventions." Journal of Gerontology. 58A, 911-916.
  7. ^ Booth FW, Chakravarthy MV, Spangenburg EE (September 2002). "Exercise and gene expression: physiological regulation of the human genome through physical activity". J. Physiol. (Lond.) (Review) 543 (Pt 2): 399–411. doi:10.1113/jphysiol.2002.019265. PMC 2290514. PMID 12205177. 
  8. ^ [non-primary source needed]Baumgartner RN, Koehler KM, Gallagher D, et al. (April 1998). "Epidemiology of sarcopenia among the elderly in New Mexico". Am. J. Epidemiol. (Comparative study) 147 (8): 755–63. PMID 9554417. 
  9. ^ a b Muscaritoli M, Anker S, Argilés J, et al. (2010). "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"". Clinical Nutrition 29 (2): 154–159. doi:10.1016/j.clnu.2009.12.004. PMID 20060626. 
  10. ^ Abate M, Di Iorio A, Di Renzo D, Paganelli R, Saggini R, Abate G (September 2007). "Frailty in the elderly: the physical dimension". Eura Medicophys 43 (3): 407–15. PMID 17117147. 
  11. ^ Faulkner JA, Larkin LM, Claflin DR, Brooks SV (November 2007). "Age-related changes in the structure and function of skeletal muscles". Clin. Exp. Pharmacol. Physiol. (Review) 34 (11): 1091–6. doi:10.1111/j.1440-1681.2007.04752.x. PMID 17880359. 
  12. ^ a b
  13. ^ Yarasheski KE (October 2003). "Exercise, aging, and muscle protein metabolism". J. Gerontol. A Biol. Sci. Med. Sci. (Review) 58 (10): M918–22. doi:10.1093/gerona/58.10.m918. PMID 14570859. 
  14. ^ a b c d Kunihiro, Sakuma; Akihiko Yamaguchi (May 28, 2012). "Sarcopenia and Age-Related Endocrine Function". International Journal of Endocrinology 2012: 127362. doi:10.1155/2012/127362. PMC 3368374. PMID 22690213. Retrieved 10 February 2014. 
  15. ^ a b Wakabayashi, H; Sakuma K (November 11, 2013). "Comprehensive Approach to Sarcopenia Treatment". Curr Clin Pharmacol. [Epub ahead of print] (2): 171–80. PMID 24219006. 
  16. ^ Finkle, WD; Greenland, S; Ridgeway, GK; Adams, JL; Frasco, MA; Cook, MB; Fraumeni, JF Jr; Hoover, RN (Jan 29, 2014). "Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men.". PLoS ONE 9 (1): e85805. doi:10.1371/journal.pone.0085805. PMC 3905977. PMID 24489673. Retrieved 2 June 2014. 
  17. ^ Vigen R; O'Donnell CI; Barón AE; Grunwald GK; Maddox TM; Bradley SM; Barqawi A; Woning G; Wierman ME; Plomondon ME; Rumsfeld JS; Ho PM (Nov 6, 2013). "Association of Testosterone Therapy With Mortality, Myocardial Infarction, and Stroke in Men With Low Testosterone Levels". JAMA 310 (17): 1829–36. doi:10.1001/jama.2013.280386. PMID 24193080. 
  18. ^ Basaria, S.; Coviello, A.D.; Travison, T.G. (June 2010). "Adverse Events Associated with Testosterone Administration". The New England Journal of Medicine 363 (2): 109–122. doi:10.1056/NEJMoa1000485. PMC 3440621. PMID 20592293. 
  19. ^ a b Lynch, Gordon S (November 2004). "Emerging drugs for sarcopenia: age-related muscle wasting". Expert Opinion on Emerging Drugs 9 (2): 345–61. doi:10.1517/14728214.9.2.345. PMID 15571490. Retrieved 3 March 2014. 
  20. ^ see press release on businesswire from 12 November 2013 "Mid-Stage Clinical Study of Wasting Disease Therapeutic MT-102 Shows Reversal of Cancer-Related Wasting"
  21. ^ Pötsch MS, Tschirner A, Palus S, von Haehling S, Doehner W, Beadle J, Coats AJ, Anker SD, Springer J (Nov 2013). "The anabolic catabolic transforming agent (ACTA) espindolol increases muscle mass and decreases fat mass in old rats". J Cachexia Sarcopenia Muscle 5 (Online ahead of print): 149–58. doi:10.1007/s13539-013-0125-7. PMC 4053568. PMID 24272787. Retrieved 28 April 2014. 
  22. ^
  23. ^ [non-primary source needed] Fried LP, Tangen CM, Walston J, et al. (2001). "Frailty in Older Adults: Evidence for a Phenotype.". J Gerontol a Biol Sci Med Sci. 56 (3): M146–56. doi:10.1093/gerona/56.3.m146. PMID 11253156. 

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