Sarcopenia is severe age-associated loss of muscle mass that causes limitations in activities of daily living and an increased mortality in affected persons, especially those who have obese sarcopenia (the 'fat frail').

The causes of sarcopenia are multifactorial (Table 3). Aging itself is associated with a decline in physical activity. Small increases in cytokines, especially interleukin (IL)-6, have been implicated in the proteolysis of muscle involved in the pathophysiology of sarcopenia [32]. Decreased food intake can lead to loss of muscle protein, as it is broken down for use in more essential proteins. The amino acid creatine is found only in meat and is essential for muscle function. Older persons who are anorectic or vegetarian have inadequate crea-tine intake for muscle maintenance.

With aging, testosterone levels decrease because of failure of the hypothalamic-pituitary-gonadal axis [33]. The decline in testosterone occurs at the rate of about 1% per year, beginning at 30 years of age. Loss of testosterone leads to an increase in adipocyte precursors and a decrease in satellite precursors. In addition, it is associated with a decline in muscle-protein synthesis. Testosterone replacement in older persons increases muscle mass and, to a lesser degree, muscle strength [34].

Myostatin is a protein that blocks muscle synthesis. Mice made transgenic for myostatin have a marked decrease in muscle mass, mimicking cachexia [35]. Recently, a human with a double deletion of the myostatin gene was reported to have muscle hypertrophy [36].

Table 3. Causes of sarcopenia Aging

Physical inactivity Anorexia

Decreased creatine intake Peripheral vascular disease Hypogonadism Cytokine excess Myostatin excess

A final cause of sarcopenia is atherosclerosis, which causes peripheral vascular disease. This is associated with decreased muscle mass and strength in the lower extremities, as well as decreased mobility.

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