Sarcopenia (from the Greek meaning "poverty of flesh") is the degenerative loss of skeletal muscle mass (0.5-1% loss per year after the age of 25), quality, and strength associated with aging. Sarcopenia is a component of the frailty syndrome. It can be differentiated from cachexia in that cachexia includes malaise and is secondary to an underlying pathosis (such as cancer), whereas 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 so much as a medical sign, because the degree to which it is normal (physiologic) versus abnormal (pathologic) is not at all clear-cut or universal. It is normal in the sense that some slight degree of it happens to almost everyone as they age. But it can be pathologic when it is excessive, which it is in many people.
- 1 Definition of sarcopenia
- 2 Elements of sarcopenia
- 3 Benefit of exercise
- 4 Fiber-type changes in sarcopenia
- 5 Loss of satellite cell function
- 6 Loss of anabolic signals
- 7 Sarcopenia as a public-health problem
- 8 Natural history
- 9 Evolutionary Considerations
- 10 Diagnosis
- 11 Management
- 12 See also
- 13 References
- 14 External sources and links
Definition of sarcopenia
The European Working Group on Sarcopenia in Older People (EWGSOP) has developed a practical clinical definition and consensus diagnostic criteria for age-related sarcopenia. For the diagnosis of sarcopenia, the working group has proposed using the presence of both low muscle mass and low muscle function (strength or performance).
Elements of sarcopenia
Sarcopenia is characterized first by a muscle atrophy (a decrease in the size of the muscle), along with a reduction in muscle tissue "quality," caused 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. Combined, these changes lead to progressive loss of muscle function and frailty.
Benefit of exercise
Lack of exercise is currently thought to be a significant risk factor for sarcopenia. Not only muscle but the entire musculoskeletal system of muscle, neuromuscular responsiveness, endocrine function, vasocapillary access, tendon, joint, ligament, and bone, depends on regular and lifelong exercise to maintain integrity. Exercise and increases in activity have been shown to be beneficial in settings of sarcopenia, even in the very old.
However, even highly trained athletes experience the effects of sarcopenia. Even Master class athletes who continue to train and compete throughout their adult life, exhibit a progressive loss of muscle mass and strength, and records in speed and strength events decline progressively after age 30.
Fiber-type changes in sarcopenia
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.
Loss of satellite cell function
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. Therefore, the ability to repair damaged muscles or respond to nutritional signals is impaired.
Loss of anabolic signals
Sarcopenia as a public-health problem
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.
Strength losses with ageing for men and women are relatively similar. They are greater for lower than upper extremity muscles. Maximum attainable strength peaks in mid-twenties and declines thereafter. The decline is precipitous after 65 years of age, though few longitudinal studies exist on this topic. A direct assessment of the effects of sarcopenia, even in extremely physically fit individuals, can be seen in the age-related decline in Masters athletics (track and field) world records of muscle-intensive sports, such as weight lifting.
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. Muscle mass has an ancient evolutionary history. The portion of the human genome which currently determines anatomy and physiology of our species evolved between 10,000 and 50,000 years ago. There was a selection advantage over larger muscle mass in the late Paleolithic, resulting in an environmental mismatch between our genome and recent sedentary lifestyle. This opens up many doors in the research of differential gene expression to the molecular basis of sarcopenia.
Aging may seem to be a mystery. Senescence, the bodily process of deterioration that occurs as age increases, can be found in many species. Senescence decreases Fitness (biology) more than all other forces of selection combined. Thus the theory that Natural selection has not yet had the opportunity to eliminate the Genes linked to senescence is challenged by the idea that the forces of natural selection become weaker as age increases. Proximate causes of muscle wasting is related to free radicals, or Oxidative stress. These reactive molecules damage any tissue which comes in contact with them. The body has developed defenses, Superoxide dismutase, (SOD) which neutralizes free radicals before the damage is done. Nature seems to fix this problem by synthesizing SOD, because muscle wasting is proximately related to abnormal levels of SOD.
This is a two-sided argument in that damage by free radicals is a proximate cause of sarcopenia, but alternatively, it is a demonstration on how natural selection works to adjust defenses. There are medical implications in that the mechanism of muscle wasting may be a trade-off equalized by natural selection. The genes involved often contain a vital function. These genes do not become deleterious until after reproductive age, thus making them not a focus of natural selection. Continued research in senescence and muscle wasting diseases is hopeful that prevention or postponing disease will allow the aging process to be comfortable and offer a higher quality of life to the end.
Consensus on clinical diagnosis of sarcopenia has quickly developed over the last decade around the working definition 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.
This methodology is attractive for definitive diagnosis in clinical settings as well for several reasons. Primarily, emerging research 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.
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:
- 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).
However, it can be replaced by one of the well-established functional tests utilized locally as being part of the comprehensive geriatric assessment.
There remain many opportunities 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. Work toward this objective has already begun, and the body of research to date clearly points toward severe sarcopenia being predicative of negative outcomes, similar to those already shown to exist with the Frailty syndrome, as defined by the criteria set forth in 2001 by Fried et al.
Exercise has been considered of great interest in treatment of sarcopenia. There are several reports showing increased ability and capacity of skeletal muscle to synthesize proteins in response to short term resistance exercise. Also, it has been reported exercise can improve physical performance (strength and mobility) in elderly subjects. However, there is insufficient research demonstrating such findings in long term.
Currently, there are no agents approved for treatment of sarcopenia. Possible therapeutic strategies include use of testosterone or anabolic steroids, though long term use of these agents is controversial in men given concerns of prostate symptoms, and essentially contraindicated in women, given concerns of virilization. Recent experimental results have shown testosterone treatments may induce adverse cardiovascular events. Other approved medications have been shown to have little to no effect in this setting, including agents such DHEA and human growth hormone. New therapies in clinical development hold great promise in this area, including the selective androgen receptor modulators (SARMs), as evidenced by recent studies. Nonsteriodal SARMs are of particular interest, given they exhibit significant selectivity between the anabolic effects of testosterone on muscle, but apparently with little to no androgenic effects such as prostate stimulation in men or virilization in women.
Diet and nutrition
Nutritional evaluation may also be indicated if malnutrition is suspected, or current nutritional intake is insufficient to maintain adequate total body mass, although increased exercise also increases appetite. A 2012 study of 14 elderly women in Scotland had "compelling" results, suggesting the fatty acids EPA and DHA contribute to increased muscle strength. A further trial involving 60 people (males and females) received funding and was due to start afterwards.
- Visser, M. (October 2009). "Towards a definition of sarcopenia--results from epidemiologic studies". The Journal of Nutrition, Health & Aging 13 (8): 713–716. PMID 19657555. "The age-related loss of muscle mass, also called sarcopenia, is receiving increasing attention in aging research. While the concept is frequently being used in research settings and introduced to clinical settings, thus far no consensus on its definition has been established. This article provides an overview of the history of sarcopenia definitions proposed in the literature thus far. It will describe the methodology used to develop the cutpoints for low muscle mass (or strength) in large epidemiological studies, how sarcopenia based on these cutpoints relates to functional outcomes, and the advantages and disadvantages of the different definitions. This overview will contribute to the current need to develop a consensus definition of sarcopenia which can be used in all relevant settings."
- Cruz-Jentoft, A. J.; Baeyens, J. P.; Bauer, J. M.; Boirie, Y.; Cederholm, T.; Landi, F.; Martin, F. C.; Michel, J. -P. et al. (2010). "Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People". Age and Ageing 39 (4): 412–423. doi:10.1093/ageing/afq034. PMC 2886201. PMID 20392703.
- Ryall, James G.; Jonathan D. Schertzer, Gordon S. Lynch (2008 Aug). "Cellular and molecular mechanisms underlying age-related skeletal muscle wasting and weakness". Biogerontology 9 (4): 213–28. doi:10.1007/s10522-008-9131-0. PMID 18299960.
- 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.
- Faulkner, John A; Lisa M Larkin, Dennis R Claflin, Susan V Brooks (2007 Nov). "Age-related changes in the structure and function of skeletal muscles". Clinical and Experimental Pharmacology and Physiology 34 (11): 1091–6. doi:10.1111/j.1440-1681.2007.04752.x. PMID 17880359.
- Doherty TJ (2003). "Invited review: Aging and sarcopenia". J Appl Physiol 95 (4): 1717–27. doi:10.1152/japplphysiol.00347.2003. PMID 12970377.
- Marcell, Taylor (October 2003). "Review Article. Sarcopenia: Causes, Consequences, and Preventions.". Journal of Gerontology: MEDICAL SCIENCES 58A (10): 911–916.
- Booth, Frank; Manu Chakravarthy, Espen Spangenburg (2002). "Exercise and gene expression: physiological regulation of the human genome through physical activity". Journal of Physiology 543 (2): 399–411. doi:10.1113/jphysiol.2002.019265.
- Nesse, Randolph; George Williams (1996). "8". Why We Get Sick: The New Science of Darwinian Medicine. New York, NY: Vintage Books. pp. 108–122. ISBN 978-0-679-74674-4.
- Schrager, Matthew; Stefania Bandinelli, Stefania Maggi, and Luigi Ferrucci (2003). "Sarcopenia: Twenty Open Question for a Research Agenda". Basic Appl Myol 13 (4): 203–208.
- Baumgartner, R.N.; Koehler, K.M.; Gallagher, D.; Romero, L.; Heymstleld, S.B.; Ross, R.R.; Garry, P.J.; Lindeman, R.D. (April 1998). "Epidemiology of sarcopenia among the elderly in New Mexico". American Journal of Epidemiology 147 (8): 755–763. PMID 9554417.
- 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.
- 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. PMID 11253156.
- Hasten, D. L.; Pak-Loduca, J.; Obert, K. A.; Yarasheski, K. E. (April 2000). "Resistance exercise acutely increases MHC and mixed muscle protein synthesis rates in 78-84 and 23-32 yr olds". American Journal of Physiology Endocrinology and Metabolism 278 (4): E620–E626. PMID 10751194.
- Yarasheski, K. E. (October 2003). "Exercise, aging, and muscle protein metabolism". The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences 58 (10): M918–M922. PMID 14570859.
- 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. PMID 20592293.
- Lynch, Gordon S (2004 Nov). "Emerging drugs for sarcopenia: age-related muscle wasting". Expert Opinion on Emerging Drugs 9 (2): 345–61. PMID 15571490.
- Ball, Jonathan (6 September 2012). "Fish oils 'help slow age decline'". BBC News. Retrieved 6 September 2012.
- 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.
- Lynch, G.S. (May 2004). "Tackling Australia's future health problems: developing strategies to combat sarcopenia—age-related muscle wasting and weakness". Internal Medicine Journal 34 (5): 294–6. doi:10.1111/j.1444-0903.2004.00568.x. PMID 15151679.
- Edström, E.; Ulfhake, B. (April 2005). "Sarcopenia is not due to lack of regenerative drive in senescent skeletal muscle". Aging Cell 4 (2): 65–77. doi:10.1111/j.1474-9728.2005.00145.x. PMID 15771610.
- Fujita, S.; Volpi, E. (January 2006). "Amino acids and muscle loss with aging". The Journal of Nutrition 136 (1 Suppl): 277S–80S. PMID 16365098.
- Visser, Marjolein; Deeg D, Lips P (2003). "Low vitamin D and high parathyroid hormone levels as determinants of loss of muscle strength and muscle mass (sarcopenia)". The Journal of Clinical Endocrinology & Metabolism 88 (12): 5766–5772. doi:10.1210/jc.2003-030604. PMID 14671166. Retrieved 2007-11-06.
- Andrew Pollack (August 30, 2010). "Doctors Seek Way to Treat Muscle Loss". New York Times.