Sarcopenia

Sarcopenia (from the Greek meaning "poverty of flesh") is the degenerative loss of skeletal muscle mass and strength associated with aging (0.5-1% loss per year after the age of 25). Sarcopenia is a component of the frailty syndrome.

Definition of sarcopenia
At present, there is no generally accepted definition of sarcopenia in the medical literature.

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 + low muscle function (strength or performance).

Markers of sarcopenia
Sarcopenia is characterized first by a decrease in the size of the muscle, which causes weakness and frailty. However, this loss of muscle mass may be caused by different cellular mechanisms than those that cause muscle atrophy. For example, during sarcopenia, there is a replacement of muscle fibres with fat and an increase in fibrosis.

Benefit of exercise
Exercise and increases in activity have been shown to be beneficial in settings of sarcopenia; exercise even in the very old can increase strength and muscle function.

Lack of exercise is currently thought to be a significant risk factor, increasing the likelihood of 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. The slow attenuation, atrophy, or loss of muscle tissue that medical professionals sometimes describe as sarcopenia (literally, "flesh loss') is currently thought to be the result of cumulative loss of musculoskeletal strength and mass associated with chronic absence of exercise of sufficient intensity or volume. However, even highly trained athletes experience the effects of sarcopenia. It is interesting to note that athletic speed and strength records are generally set by individuals no older than 30 years of age, although some powerlifters and other strength athletes continue to set records into their 50s.

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). However, we lose both type I and type II muscle fibers (muscle cells) equally as we age (contrary to popular belief that we lose type II more rapidly).

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
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.

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.

Natural history
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.

Diagnosis
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 later 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 remains many opportunities for further refinement of reference populations by ethnic groups, and to further correlate of 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 is predicative of negative outcomes, similar to what already been shown to exist with the Frailty syndrome, as defined by the criteria set forth in 2001 by Fried et al.

Exercise
Primary management of sarcopenia is through the application of a graded exercise program, across both cardiovascular and strength domains, dosed in such a way as to provoke beneficial adaptation without overloading the weakened body. Physical activity incorporating resistance training is probably the most effective measure to prevent and treat sarcopenia.

Drugs
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.

External sources and links

 * "Doctors Seek Way to Treat Muscle Loss,' by ANDREW POLLACK, New York Times, August 30, 2010
 * "Doctors Seek Way to Treat Muscle Loss,' by ANDREW POLLACK, New York Times, August 30, 2010
 * "Doctors Seek Way to Treat Muscle Loss,' by ANDREW POLLACK, New York Times, August 30, 2010
 * "Doctors Seek Way to Treat Muscle Loss,' by ANDREW POLLACK, New York Times, August 30, 2010
 * "Doctors Seek Way to Treat Muscle Loss,' by ANDREW POLLACK, New York Times, August 30, 2010
 * "Doctors Seek Way to Treat Muscle Loss,' by ANDREW POLLACK, New York Times, August 30, 2010

Sarkopenie Sarcopenia Sarcopénie Sarcopenia Sarcopenia Саркопения Sarkopenia