Sarcopenia Should Reflect the Contribution of Age-Associated Changes in Skeletal Muscle to Risk of Morbidity and Mortality in Elderly People

Abstract

The loss of skeletal muscle mass with advancing age is a universal phenomenon. The trajectory of this loss of muscle is remarkably variable and its etiology complex and multifactorial. The term, sarcopenia, was initially described as the age-associated decrease in skeletal muscle mass and was thought to be similar to the phenomenon of osteopenia, the age associated loss of bone density that is predictive of an increase in risk of a bone fracture.1,2 The loss of muscle mass was thought to be the primary cause of decreased strength and functional capacity and a predictor of risk of disability or other outcomes. Indeed, a cross-sectional study with a wide range of ages from my laboratory seemed to confirm this idea, when we found that there were no significant age-associated differences in muscle strength when strength was expressed as a function of muscle mass.3 Frontera et al4 demonstrated that 90% of the loss in strength over 12 years was explained by decreased muscle cross-sectional area and initial muscle strength. However, a number of longitudinal studies have demonstrated that the loss of skeletal muscle mass and force production is not tightly linked, and among very old men and women, muscle size explains only 6% of the variability in muscle strength.5 In general, there is a greater loss of muscle strength than mass and weakness appears to be more closely associated with risk of disability and mortality.6 However, there are a number of ageassociated changes in many properties of skeletal muscle that may contribute to morbidity and mortality.7 Skeletal muscle is the primary site of glucose disposal and resistance of glucose transport into muscle is strongly associated with risk of type 2 diabetes along with a sequelae of conditions including microvascular disease, neuropathy, nephropathy, and eye damage (including cataract). Decreased muscle mass is the largest contributor to the ageassociated decrease in basal metabolic rate,8 and the reduced energy requirement of elderly people to the well-characterized increased body fatness in elderly people. The broad range of metabolic and contractile changes that occur with advancing age and their contribution not only to weakness but to many of the diseases of aging should cause a rethinking of the term sarcopenia and what components of muscle function and metabolism should be measured to assess morbidity and mortality9 and how better to define sarcopenia.