Sarcopenia: normal versus pathologic
Steven B. Heymsfield (Louisiana State University) shifted the focus to examine aging-related diseases. A long-recognized age-related phenomenon, sarcopenia— the gradual aging-related loss of skeletal muscle mass with associated changes in muscle quality and function—is a clinically important component of frailty and some metabolic disturbances. Sarcopenia is the focus of active research programs aimed at understanding underlying mechanisms in order to develop preventive and therapeutic measures. Gradual loss of skeletal muscle mass is a normal part of the aging process, related to increasing inactivity. It can also be caused by underlying catabolic illness, usually referred to as cachexia, which differs metabolically from classical sarcopenia. Thus, sarcopenia is classified as primary or secondary (inactivity versus cachexia); primary sarcopenia appears in stages, beginning with pre-sarcopenia, advancing to clinically manifest sarcopenia, and finally to severe sarcopenia.
Recently sarcopenia has been recognized in obese individuals, a comorbidity referred to as sarcopenic obesity. As might be expected from two conditions that individually pose increased risk, sarcopenic obesity is associated with greater morbidity risk than either condition alone.
Skeletal muscle mass reaches peak values during the late teen years and early twenties, and then begins to slowly decline in healthy adults at a rate of about 0.5–1% per year. Age-related rates of skeletal muscle mass loss vary; individuals with rapid muscle loss are at risk for sarcopenia, as are those with rapid bone loss and osteoporosis. Determinants of skeletal muscle mass include genetic susceptibility, height, activity level, race, adiposity, and abnormal levels of key hormones.
Heritability estimates for human skeletal muscle (lean) mass is ∼ 0.52, with similar corresponding estimates for leg extensor and grip strength. Myostatin is a gene that regulates skeletal muscle mass; inactivation leads to significantly larger skeletal muscles in mammals. Taller adults have more skeletal muscle than their shorter counterparts. Skeletal muscle scales with the square of height, similar to body weight. Analogous to body mass index (BMI; weight/height2), skeletal muscle mass index (SM/height2) adjusts for individual differences in height, allowing for the definition of diagnostic criteria for sarcopenia. People who exercise regularly have greater skeletal muscle mass. A large percentage of Americans have suboptimal levels of leisure time physical activity, particularly the elderly. On average, African Americans have more skeletal muscle mass than Caucasians matched for weight, height, and age, through unknown mechanisms. Anabolic hormones, such as androgens, growth hormone, and IGF-1, stimulate growth and maintenance of skeletal muscle mass, effects that decline with aging, particularly from the sixth decade onward. Finally, greater skeletal muscle mass develops with larger mechanical loads. Thus, obese people tend to have more skeletal muscle than age-matched counterparts; the proportion of fat-free mass as skeletal muscle increases with greater adiposity.
While the classical approach to sarcopenia focuses on skeletal muscle mass, growing interest surrounds dynapenia, or loss in muscle strength. Functional limitations, frailty, and other consequences of age-related changes in muscle strength are of central importance to the morbidity and mortality associated with sarcopenia. Beginning around the seventh decade and progressing beyond, rates of loss of skeletal muscle function exceed those of mass. Functional effects are very slow to return following periods of illness and lack of activity.
Obviously, sarcopenia results from multiple interacting factors, the mechanisms of which remain to be determined. Skeletal muscle does not develop in isolation; it grows during development and declines with senescence under the influence of neural and hormonal regulation. These factors influence skeletal muscle mass and function and contribute to the pathogenesis of sarcopenia. For example, an elderly person's fall with injury may be attributable to insufficient skeletal muscle mass with poor functional quality (poor leg strength and coordination), as well as to a series of neurocognitive and neuromuscular pathways functioning below optimal levels. Thus, it is only within a broader physiological context that a full understanding of sarcopenia and its clinical manifestations will evolve.
Skeletal muscle power: a determinant of physical functioning in older adults
Roger A. Fielding (Tufts University) discussed the importance of muscle power output as one of the variables that contribute to physical impairment associated with aging. Skeletal muscle, the largest organ mass in the body, making up 40–50% of total body mass, is required for locomotion and is a determinant of oxygen consumption, whole body energy metabolism, and substrate turnover and storage. Advancing age is associated with the loss of skeletal muscle (sarcopenia), and can lead to declines in physical functioning. The causes of sarcopenia, like many complex geriatric syndromes, are multifactorial. The loss of muscle mass and strength, and the concurrent increase in joint dysfunction and arthritis that occurs with aging, results in a decrease in physical function and an increased risk of disability. Disability is associated with limitations in performing regular activities of daily living, including rising from a chair, climbing flights of stairs, bathing, and preparing food. Studies have shown that the ability to perform these tasks decreases with age in both men and women.
Despite the high prevalence and major health implications, sarcopenia still has no broadly accepted clinical definition or diagnostic criteria. The most current definition of sarcopenia includes gait speed < 1.0 m/s combined with a low ratio of appendicular lean mass (aLM) to height squared (≤ 7.23 kg/m2 in males, ≤ 5.67 kg/m2 in women), two standard deviations below the mean aLM of young healthy adults.
Skeletal muscle power output (the product of force and velocity) declines earlier and more precipitously with advancing age compared to muscle strength. In cross-sectional and longitudinal studies of older adults, Fielding and colleagues observed that declines in muscle mass could not fully explain the observed deficits in skeletal muscle power output, suggesting that factors related to deficits in neuromuscular activation may play a role. Fielding reported significant reductions in neuromuscular activation patterns and deficits in rapid activation of voluntary lower extremity muscle groups in older adults with measured limitations in physical functioning. Peak muscle power has also emerged as an important predictor of functional limitations in older adults, and as an important outcome measure in clinical trials of resistance training of older adults. Fielding explained that his group's current working hypothesis is focused on examining lower extremity muscle power as a more critical variable in understanding the relationship between impairments, functional limitations, and resultant disability with aging.