Sarcopenia is a type of muscle loss (muscle atrophy) that occurs with aging and/or immobility. It is characterized by the degenerative loss of skeletal muscle mass, quality, and strength. The rate of muscle loss is dependent on exercise level, co-morbidities, nutrition and other factors. The muscle loss is related to changes in muscle synthesis signalling pathways. It is distinct from cachexia, in which muscle is degraded through cytokine-mediated degradation, although both conditions may co-exist. Sarcopenia is considered a component of frailty syndrome. Sarcopenia can lead to reduced quality of life, falls, fracture, and disability.
Sarcopenia is a factor in changing body composition associated with aging populations; and certain muscle regions are expected to be affected first, specifically the anterior thigh and abdominal muscles. In population studies, body mass index (BMI) is seen to decrease in aging populations while bioelectrical impedance analysis (BIA) shows body fat proportion rising.
The term sarcopenia is from Greek σάρξ sarx, "flesh" and πενία penia, "poverty". This was first proposed by Rosenberg in 1989, who wrote that "there may be no single feature of age-related decline that could more dramatically affect ambulation, mobility, calorie intake, and overall nutrient intake and status, independence, breathing, etc. Why have we not given it more attention? Perhaps it needs a name derived from the Greek. I'll suggest a couple: sarcomalacia or sarcopenia".
Signs and symptoms
The hallmark sign of sarcopenia is loss of lean muscle mass, or muscle atrophy. The change in body composition may be difficult to detect due to obesity, changes in fat mass, or edema. Changes in weight, limb or waist circumference are not reliable indicators of muscle mass changes. Sarcopenia may also cause reduced strength, functional decline and increased risk of falling. Sarcopenia may also have no symptoms until it is severe and is often unrecognized. Research has shown, however, that hypertrophy may may occur in the upper parts of the body to compensate for this loss of lean muscle mass Therefore, one indicator of the early onset of sarcopenia can be seen when significant loss of muscle mass in the anterior thigh and abdominal muscles.
There are many proposed causes of sarcopenia and it is likely the result of multiple interacting factors. Understanding of the causes of sarcopenia is incomplete, however changes in hormones, immobility, age-related muscle changes, nutrition and neurodegenerative changes have all been recognized as potential causative factors.
The degree of sarcopenia is determined by two factors: initial amount of muscle mass and rate at which muscle mass declines. Due to variations in these factors across the population, the rate of progression and the threshold at which muscle loss becomes apparent is variable. Immobility dramatically increases the rate of muscle loss, even in younger people. Other factors that can increase rate of progression of sarcopenia include decreased nutrient intake, low physical activity, or chronic disease. Additionally, epidemiological research has indicated that early environmental influences may have long-term effects on muscle health. For example, low birth weight, a marker of a poor early environment, is associated with reduced muscle mass and strength in adult life.
There are multiple theories proposed to explain the mechanisms of muscle changes of sarcopenia including changes in satellite cell recruitment, changes in anabolic signalling, protein oxidation, inflammation, and developmental factors. The pathologic changes of sarcopenia include a reduction in muscle tissue quality as reflected in the replacement of muscle fibers with fat, an increase in fibrosis, changes in muscle metabolism, oxidative stress, and degeneration of the neuromuscular junction.
The distribution of muscle fibers types also changes in sarcopenic muscle causing a decrease in type II muscle fibers, or "fast twitch," with little to no decrease in type I muscle fibers, or "slow-twitch" muscle fibers. Deinervated type II fibers are often converted to type I fibers by reinnervation by slow type I fiber motor nerves.
The failure to activate satellite cells upon injury or exercise is also thought to contribute to the pathophysiology of sarcopenia. Additionally, oxidized proteins can lead to a buildup of lipofuscin and cross-linked proteins causing an accumulation of non-contractile material in the skeletal muscle and contribute to sarcopenic muscle.
Multiple diagnostic criteria have been proposed by various expert groups and continues to be an area of research and debate. Despite the lack of a widely accepted definition, sarcopenia was assigned an ICD-10 code (M62.84) in 2016, recognizing it as a disease state.
Sarcopenia can be diagnosed when a patient has muscle mass that is at least two standard deviations below the relevant population mean and has a slow walking speed. The European Working Group on Sarcopenia in Older People (EWGSOP) developed a broad clinical definition for sarcopenia, designated as the presence of low muscle mass and either low muscular strength or low physical performance. Other international groups have proposed criteria that include metrics on walking speed, distance walked in 6 minutes, or grip strength. Hand grip strength alone has also been advocated as a clinical marker of sarcopenia that is simple and cost effective and has good predictive power, although it does not provide comprehensive information.
There are screening tools for sarcopenia that assess patient reported difficulty in doing daily activities such as walking, climbing stairs or standing from a chair and have been shown to predict sarcopenia and poor functional outcomes.
Exercise remains the intervention of choice for sarcopenia, but translation of research findings into clinical practice is challenging. The type, duration and intensity of exercise are variable between studies, preventing a standardized exercise prescription for sarcopenia. Lack of exercise is a significant risk factor for sarcopenia and exercise can dramatically slow the rate of muscle loss. Exercise can be an effective intervention because aging skeletal muscle retains ability to synthesize proteins in response to short-term resistance exercise. Progressive resistance training in older adults can improve physical performance (gait speed) and muscular strength.
There are currently no approved medications for the treatment of sarcopenia. 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. Additionally, recent studies suggest testosterone treatments may induce adverse cardiovascular events.
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. 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.
Intake of calories and protein are important stimuli for muscle protein synthesis. Older adults may not utilize protein as efficiently as younger people and may require higher amounts to prevent muscle atrophy. A number of expert groups have proposed an increase in dietary protein recommendations for older age groups to 1.0-1.2 g/kg body weight per day. Ensuring adequate nutrition in older adults is of interest in the prevention of sarcopenia and frailty, since it is a simple, low-cost treatment approach without major side effects.
A component of sarcopenia is the loss of ability for aging skeletal muscle to respond to anabolic stimuli such as amino acids, especially at lower concentrations. However, aging muscle retains the ability of an anabolic response to protein or amino acids at larger doses. Supplementation with larger doses of amino acids, particularly leucine has been reported to counteract muscle loss with aging. Exercise may work synergistically with amino acid supplementation.
β-hydroxy β-methylbutyrate (HMB) is a metabolite of leucine that acts as a signalling molecule to stimulate protein synthesis. It is reported to have multiple targets, including stimulating mTOR and decreasing proteasome expression. Its use to prevent the loss of lean body mass in older adults is consistently supported in clinical trials. More research is needed to determine the precise effects of HMB on muscle strength and function in this age group.
The prevalence of sarcopenia depends on the definition used in each epidemiological study. Estimated prevalence in 60-70 year old people is 5-13% and increases to 11-50% in people over 80 years of age. This equates to >50 million people and is projected to affect >200 million in the next 40 years given the rising population of older adults.
Public health impact
Sarcopenia is emerging as a major public health concern given the increased longevity of industrialized populations and growing geriatric population. Sarcopenia is a predictor of many adverse outcomes including increased disability, falls and mortality. Immobility or bed rest in populations predisposed to sarcopenia can cause dramatic impact on functional outcomes. In the elderly, this often leads to decreased biological reserve and increased vulnerability to stressors known as the "frailty syndrome". Loss of lean body mass is also associated with increased risk of infection, decreased immunity, and poor wound healing. The weakness that accompanies muscle atrophy leads to higher risk of falls, fractures, physical disability, need for institutional care, reduced quality of life, increased mortality, and increased healthcare costs. This represents a significant personal and societal burden and its public health impact is increasingly recognized.
There are significant opportunities to better understand the causes and consequences of sarcopenia and help guide clinical care. This includes elucidation of the molecular and cellular mechanisms of sarcopenia, further refinement of reference populations by ethnic groups, validation of diagnostic criteria and clinical tools, as well as tracking of incidence of hospitalization admissions, morbidity, and mortality. Identification and research on potential therapeutic approaches and timing of interventions is also needed.
New pharmaceutical therapies in clinical development include myostatin and the selective androgen receptor modulators (SARMs). 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).
- Peterson SJ, Mozer M (February 2017). "Differentiating Sarcopenia and Cachexia Among Patients With Cancer". Nutrition in Clinical Practice. 32 (1): 30–39. doi:10.1177/0884533616680354. PMID 28124947. S2CID 206555460.
- Ata AM, Kara M, Kaymak B, Ozcakar L. Sarcopenia Is Not "Love": You Have to Look Where You Lost it!. Am J Phys Med Rehabil. 2020;99(10):e119-e120. doi:10.1097/PHM.0000000000001391.
- Beaudart C, Zaaria M, Pasleau F, et al: Health outcomes of sarcopenia: a systematic reviewand meta-analysis.PLoS One2017;12:e0169548
- Ata AM, Kara M, Kaymak B, et al: Regional and total muscle mass, muscle strength andphysical performance: the potential use of ultrasound imaging for sarcopenia.Arch GerontolGeriatr2019;83:55–60
- Ranasinghe, Chathuranga; Gamage, Prasanna (2013). "Relationship between Body mass index (BMI) and body fat percentage, estimated by bioelectrical impedance, in a group of Sri Lankan adults: a cross sectional study". BMC Public Health. 13: 797. doi:10.1186/1471-2458-13-797. PMC 3766672. PMID 24004464.
- Özkal Ö, Kara M, Topuz S, et al: Assessment of core and lower limb muscles forstatic/dynamic balance in the older people: an ultrasonographic study.Age Ageing2019;48:881–7
- Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, et al. (July 2010). "Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People". Age and Ageing. 39 (4): 412–23. doi:10.1093/ageing/afq034. PMC 2886201. PMID 20392703.
- Marcell TJ (October 2003). "Sarcopenia: causes, consequences, and preventions". The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences (Review). 58 (10): M911-6. doi:10.1093/gerona/58.10.m911. PMID 14570858.
- Sayer AA, Syddall HE, Gilbody HJ, Dennison EM, Cooper C (September 2004). "Does sarcopenia originate in early life? Findings from the Hertfordshire cohort study". The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 59 (9): M930-4. doi:10.1093/gerona/59.9.M930. PMID 15472158.
- Gale CR, Martyn CN, Kellingray S, Eastell R, Cooper C (January 2001). "Intrauterine programming of adult body composition". The Journal of Clinical Endocrinology and Metabolism. 86 (1): 267–72. doi:10.1210/jcem.86.1.7155. PMID 11232011.
- Ylihärsilä H, Kajantie E, Osmond C, Forsén T, Barker DJ, Eriksson JG (September 2007). "Birth size, adult body composition and muscle strength in later life". International Journal of Obesity. 31 (9): 1392–9. doi:10.1038/sj.ijo.0803612. PMID 17356523.
- 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. S2CID 8576449.
- Doherty TJ (October 2003). "Invited review: Aging and sarcopenia". Journal of Applied Physiology (Review). 95 (4): 1717–27. doi:10.1152/japplphysiol.00347.2003. PMID 12970377.
- Anker SD, Morley JE, von Haehling S (December 2016). "Welcome to the ICD-10 code for sarcopenia". Journal of Cachexia, Sarcopenia and Muscle. 7 (5): 512–514. doi:10.1002/jcsm.12147. PMC 5114626. PMID 27891296.
- Argilés JM, Campos N, Lopez-Pedrosa JM, Rueda R, Rodriguez-Mañas L (September 2016). "Skeletal Muscle Regulates Metabolism via Interorgan Crosstalk: Roles in Health and Disease". Journal of the American Medical Directors Association. 17 (9): 789–96. doi:10.1016/j.jamda.2016.04.019. PMID 27324808.
- Sayer AA (August 2010). "Sarcopenia". BMJ. 341 (aug10 2): c4097. doi:10.1136/bmj.c4097. PMID 20699307. S2CID 220113690.
- Malmstrom TK, Miller DK, Simonsick EM, Ferrucci L, Morley JE (March 2016). "SARC-F: a symptom score to predict persons with sarcopenia at risk for poor functional outcomes". Journal of Cachexia, Sarcopenia and Muscle. 7 (1): 28–36. doi:10.1002/jcsm.12048. PMC 4799853. PMID 27066316.
- Sayer AA (November 2014). "Sarcopenia the new geriatric giant: time to translate research findings into clinical practice". Age and Ageing. 43 (6): 736–7. doi:10.1093/ageing/afu118. PMID 25227204.
- Abate M, Di Iorio A, Di Renzo D, Paganelli R, Saggini R, Abate G (September 2007). "Frailty in the elderly: the physical dimension". Europa Medicophysica. 43 (3): 407–15. PMID 17117147.
- Yarasheski KE (October 2003). "Exercise, aging, and muscle protein metabolism". The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences (Review). 58 (10): M918-22. doi:10.1093/gerona/58.10.m918. PMID 14570859.
- Liu CJ, Latham NK (July 2009). "Progressive resistance strength training for improving physical function in older adults". The Cochrane Database of Systematic Reviews (3): CD002759. doi:10.1002/14651858.cd002759.pub2. PMC 4324332. PMID 19588334.
- Phillips SM (July 2015). "Nutritional supplements in support of resistance exercise to counter age-related sarcopenia". Advances in Nutrition. 6 (4): 452–60. doi:10.3945/an.115.008367. PMC 4496741. PMID 26178029.
- Sakuma K, Yamaguchi A (28 May 2012). "Sarcopenia and age-related endocrine function". International Journal of Endocrinology. 2012: 127362. doi:10.1155/2012/127362. PMC 3368374. PMID 22690213.
- Wakabayashi H, Sakuma K (May 2014). "Comprehensive approach to sarcopenia treatment". Current Clinical Pharmacology. 9 (2): 171–80. doi:10.2174/1574884708666131111192845. PMID 24219006.
- Finkle WD, Greenland S, Ridgeway GK, Adams JL, Frasco MA, Cook MB, et al. (29 January 2014). "Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men". PLOS ONE. 9 (1): e85805. Bibcode:2014PLoSO...985805F. doi:10.1371/journal.pone.0085805. PMC 3905977. PMID 24489673.
- Vigen R, O'Donnell CI, Barón AE, Grunwald GK, Maddox TM, Bradley SM, et al. (November 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.
- Basaria S, Coviello AD, Travison TG, Storer TW, Farwell WR, Jette AM, et al. (July 2010). "Adverse events associated with testosterone administration". The New England Journal of Medicine. 363 (2): 109–22. doi:10.1056/NEJMoa1000485. PMC 3440621. PMID 20592293.
- Robinson SM, Reginster JY, Rizzoli R, Shaw SC, Kanis JA, Bautmans I, et al. (August 2018). "Does nutrition play a role in the prevention and management of sarcopenia?". Clinical Nutrition. 37 (4): 1121–1132. doi:10.1016/j.clnu.2017.08.016. PMC 5796643. PMID 28927897.
- Bauer J, Biolo G, Cederholm T, Cesari M, Cruz-Jentoft AJ, Morley JE, et al. (August 2013). "Evidence-based recommendations for optimal dietary protein intake in older people: a position paper from the PROT-AGE Study Group". Journal of the American Medical Directors Association. 14 (8): 542–59. doi:10.1016/j.jamda.2013.05.021. PMID 23867520.
- Deutz NE, Bauer JM, Barazzoni R, Biolo G, Boirie Y, Bosy-Westphal A, et al. (December 2014). "Protein intake and exercise for optimal muscle function with aging: recommendations from the ESPEN Expert Group". Clinical Nutrition. 33 (6): 929–36. doi:10.1016/j.clnu.2014.04.007. PMC 4208946. PMID 24814383.
- Tessier AJ, Chevalier S (August 2018). "An Update on Protein, Leucine, Omega-3 Fatty Acids, and Vitamin D in the Prevention and Treatment of Sarcopenia and Functional Decline". Nutrients. 10 (8): 1099. doi:10.3390/nu10081099. PMC 6116139. PMID 30115829.
- Fujita, Satoshi; Volpi, Elena (1 January 2006). "Amino Acids and Muscle Loss with Aging". The Journal of Nutrition. 136 (1): 277S–280S. doi:10.1093/jn/136.1.277S. ISSN 0022-3166. PMC 3183816. PMID 16365098.
- Brioche T, Pagano AF, Py G, Chopard A (August 2016). "Muscle wasting and aging: Experimental models, fatty infiltrations, and prevention" (PDF). Molecular Aspects of Medicine. 50: 56–87. doi:10.1016/j.mam.2016.04.006. PMID 27106402.
- Wu H, Xia Y, Jiang J, Du H, Guo X, Liu X, et al. (September 2015). "Effect of beta-hydroxy-beta-methylbutyrate supplementation on muscle loss in older adults: a systematic review and meta-analysis". Archives of Gerontology and Geriatrics. 61 (2): 168–75. doi:10.1016/j.archger.2015.06.020. PMID 26169182.
- Holeček, Milan (August 2017). "Beta-hydroxy-beta-methylbutyrate supplementation and skeletal muscle in healthy and muscle-wasting conditions: HMB supplementation and muscle". Journal of Cachexia, Sarcopenia and Muscle. 8 (4): 529–541. doi:10.1002/jcsm.12208. PMC 5566641. PMID 28493406.
- Sayer AA, Robinson SM, Patel HP, Shavlakadze T, Cooper C, Grounds MD (March 2013). "New horizons in the pathogenesis, diagnosis and management of sarcopenia". Age and Ageing. 42 (2): 145–50. doi:10.1093/ageing/afs191. PMC 3575121. PMID 23315797.
- Lynch GS (November 2004). "Emerging drugs for sarcopenia: age-related muscle wasting". Expert Opinion on Emerging Drugs. 9 (2): 345–61. doi:10.1517/14728188.8.131.525. PMID 15571490. S2CID 73056527.
- Fujita S, Volpi E (January 2006). "Amino acids and muscle loss with aging". The Journal of Nutrition (Review). 136 (1 Suppl): 277S–80S. doi:10.1093/jn/136.1.277S. PMC 3183816. PMID 16365098.
- Roubenoff R (December 2007). "Physical activity, inflammation, and muscle loss". Nutrition Reviews. 65 (12 Pt 2): S208-12. doi:10.1111/j.1753-4887.2007.tb00364.x. PMID 18240550.