Sarcopenia is defined as the age-related loss of skeletal muscle mass, strength, and function. The condition is both a process and an outcome. Beginning in the fourth decade of life, adults lose 3% to 5% of muscle mass per decade,1 a rate of decline that increases to 1% to 2% per year after age 50 years.2 Muscular strength is independently associated with functionality,3-5 while loss of skeletal muscle mass and strength is associated with declining health.3 The loss of muscle mass and function can be both a fundamental cause of and a contributor to disability and disease progression.
Given its ubiquitous nature and deleterious consequences, sarcopenia is believed to have a far-reaching and costly impact on health care in America. Much of this cost could be averted, however, as sarcopenia is thought to be preventable and, to some extent, reversible. Unfortunately, most clinicians are not familiar with sarcopenia. This article presents a thorough review of the condition, discusses current treatment recommendations, and provides concrete action plans for implementing them.
Sarcopenia should be differentiated from other disorders associated with skeletal muscle loss, including 
cachexia and wasting. The term wasting was originally used to describe the rapid, unintentional loss of both muscle and adipose tissue in persons with HIV disease. Wasting results primarily from anorexia and inadequate dietary intake, with subsequent negative protein and calorie balance. Cachexia is defined as the accelerated loss of muscle mass seen with chronic inflammation caused by acute disease. It is a slower process than wasting, and its pathogenesis includes metabolic alterations resulting from a disease-mediated increase in cytokine production.6 Sarcopenia has an even more insidious course than cachexia. There are numerous underlying mechanisms behind sarcopenia, which collectively result in decreased anabolism leading to net muscle loss over time. Unlike cachexia and wasting, sarcopenia occurs in persons who are otherwise free of disease.
The progressive decline in muscle mass and strength characteristic of sarcopenia impairs functionality and eventually leads to significant morbidity, suggesting a pathologic state. The disorder is analogous to steoporosis. In that case, a disease state is defined when bone mass reaches a “zone of fracture risk” (2.5 standard deviations below the young normal mean), with fracture being the primary adverse outcome. Sarcopenia could be considered a disease when the loss of muscle mass and strength reaches the level of functional impairment or disability. Unlike for osteoporosis, however, there is no agreed-upon chief adverse outcome for sarcopenia.
In their work involving the New Mexico Elder Health Study, Baumgartner and colleagues defined sarcopenia as “lean body mass more than two standard deviations below the young normal mean.”7 This definition has been used in subsequent studies. Some researchers conclude that muscle power is a better predictor of physical function, suggesting that some measure of strength or power should be included with measurements of muscle mass when defining sarcopenia.8,9 More recent efforts focus on determining a skeletal muscle “cutpoint” that correlates with physical disability risk in the elderly.
Epidemiologic studies estimate t
he prevalence of sarcopenia to be as high as 50% in people 80 years and older.7,10,11 In 2000, health care costs attributed to the disorder were estimated to be $18.5 billion.12 This figure represents only the direct costs of sarcopenia, including hospital, outpatient, and home care expenditures. As a means of comparison, the annual economic costs of osteoporotic fractures (adjusted to 2000 dollars) were estimated to be $16.3 billion.12
Etiologies
Protein metabolism Skeletal muscle homeostasis is achieved through a continuous repair process involving the breakdown and synthesis of protein. Studies consistently find that muscle-protein synthesis rates are approximately 30% lower in older adults than in younger adults.13 Over time, this results in a net loss of muscle mass consisting of a numeric loss of muscle fibers, as well as a qualitative change in the cross-sectional area of the remaining fibers. Most atrophy is seen in the type II, or “fast twitch,” muscle fibers. Type II fibers have a high glycolytic capacity and are used for short bursts of anaerobic power.
The ability of skeletal muscle to regenerate following injury or overload decreases with age. Satellite cells, the specialized cells located in the basal membrane of the muscle cell, are necessary to develop new muscle tissue. The number of satellite cells in skeletal muscle decreases as a person ages, also contributing to the loss of muscle mass and strength.14
Hormones Levels of anabolic hormones uniformly decline with age. Testosterone declines at a rate of pproximately 100 ng/dL per decade and has been shown to parallel the decline in muscle mass and strength occurring in elderly men.15 Bioavailable testosterone levels in elderly women also are decreased, particularly immediately following menopause. However, the relationship between declining testosterone levels in women and sarcopenia has not been adequately studied.
Growth hormone (GH) is secreted in a pulsatile fashion from the pituitary gland, stimulating peripheral production
of insulinlike growth factor-1 (IGF-1). GH secretion declines steadily by approximately 14% per decade, with a proportionate decline in IGF-1 levels.16 GH deficiency results in a loss of muscle mass and an increase in adipose tissue.
Dehydroepiandrosterone sulfate (DHEAS) is an androgen produced by the adrenal cortex. It is considered to be a metabolic intermediate in the steroid hormone synthesis pathway of testosterone, estrone, and estradiol. Although the biological role of DHEAS is not precisely understood, levels decline with age in a linear fashion by 10% to 20% per decade.17
Although not an androgen, estrogen may have a role in the development of sarcopenia in women. Menopause has been linked to a reduction in lean body mass in women, independent of lifestyle factors such as diet and exercise.18
Neuromuscular changes Movement is initiated by motor neurons sending signals from the brain to the muscles. A motor neuron and all the muscle fibers it innervates make up a motor unit. The number of spinal cord motor neurons and functioning motor units declines with age, by as much as 50% after age 60 years.14 This age-associated denervation is thought to be continuous and irreversible,19 causing the muscle fibers to atrophy and motor neurons to eventually die.14
When a motor neuron dies, an adjacent—usually a “slow twitch”—motor neuron may reinnervate the muscle fibers, preventing atrophy. This process is called motor unit remodeling. A slow twitch motor unit has a slower firing rate, is slower to contract, produces less muscle force, and is smaller in both size and muscle fiber number. Ultimately, motor unit remodeling leads to a less efficient motor unit producing less precise control of movements, less force production, and an overall slowing of muscle mechanics.14,19