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Sarcopenia (ICD-10-CM code M62.84) is a type of muscle loss that occurs with aging and/or Bed rest. 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 the two 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. When associated with aging populations, 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 degree of sarcopenia is determined by two factors: the initial amount of muscle mass and the 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 the 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.
In sarcopenic muscle the distribution of the types of changes with 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. Males are perhaps more susceptible for this aging-related switching of the myofiber type, as a recent research has shown a higher percentage of "slow twitch" muscle fibers in old compared to young males, but not in old compared to young females.
Aging sarcopenic muscle shows an accumulation of mitochondrial DNA mutations, which has been demonstrated in various other cell types as well. Clones with mitochondrial mutations build up in certain regions of the muscle, which goes along with an about fivefold increase in the absolute mtDNA copy number, that is, these regions are denser. An apparent protective factor preventing cells' buildup of damaged mitochondria is sufficient levels of the protein BNIP3. Deficiency of BNIP3 leads to muscle inflammation and atrophy.
Furthermore, not every muscle is as susceptible to the atrophic effects of aging. For example, in both humans and mice it has been shown that lower leg muscles are not as susceptible to aging as upper leg muscles. This could perhaps be explained by the differential distribution of myofiber type within each muscle group, but this is unknown.
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.
Aging and sarcopenia are associated with an increase in inflammatory markers ("inflamm-aging") including: C-reactive protein, tumor necrosis factor, interleukin-8, interleukin-6, granulocyte-monocyte colony-stimulating factor, , and serine protease A1.
Changes in associated with aging and sarcopenia include a reduction in the Sex hormone testosterone and dehydroepiandrosterone sulfate, as well as reduced levels of circulating growth hormone and IGF-1.
Circulating C-terminal agrin fragments (CAF) have been found to be higher in accelerated sarcopenic patients.
Lower plasma levels of the leucine and isoleucine as well as other essential amino acids were found in frail older people compared to non-frail controls.
Alanine aminotransferase (ALT) is responsible for the transfer of the α-amino group from an α-amino acid to an α-keto acid, transforming pyruvate to alanine in skeletal muscle. Low circulating ALT is a marker for low muscle mass and sarcopenia, as well for increased disease activity in patients with inflammatory bowel disease.
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.
Other medications under investigation as possible treatments for sarcopenia include ghrelin, vitamin D, angiotensin converting enzyme inhibitors, and eicosapentaenoic acid.
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.
Sarcopenia is distinct from cachexia, in which muscle is degraded through cytokine-mediated degradation, although the two conditions may co-exist.
, there are no drugs approved to treat muscle wasting in people with chronic diseases, and there is therefore an unmet need for anabolic drugs with few side effects. One aspect hindering drug approval for treatments for cachexia and sarcopenia is disagreement in endpoints. Several clinical trials have found that selective androgen receptor modulators (SARMs) improve lean mass in humans, but it is not clear whether strength and physical function are also improved. After promising results in a phase II trial, a phase III trial of the SARM ostarine was proven to increase lean body mass but did not show significant improvement in function. It and other drugs—such as the growth hormone secretagogue anamorelin—have been refused regulatory approval despite significant increases in lean mass due to a lack of evidence that they increased physical performance. Preventing decline in functionality was not considered an acceptable endpoint by the Food and Drug Administration. It is not known how SARMs interact with dietary protein intake and resistance training in people with muscle wasting.
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