Stalking Sarcopenia

Among the most dramatic biological markers of increasing age are changes in body composition. Although weight may remain stable or increase somewhat throughout adulthood, fat-free mass steadily decreases and fat mass as a percentage of body weight therefore increases [1]. This age-related change is even more impressive if the decrease in muscle mass is measured rather than the decrease in lean body mass or fat-free mass, which includes viscera and bone. The rate of decline by decade is particularly great after age 70 years; this can be confirmed by direct regional assessments of the cross-sectional area of skeletal muscle in images produced by computed tomography. At the mid-thigh level, for example, muscle accounts for 90% of the cross-sectional area in active young men but only 30% of that area in frail elderly women. The average woman's lean body mass is always smaller than that of men at the same age, but the decline is striking nonetheless. Some studies, including the report by Poehlman and colleagues in this issue [2], have shown an accelerated decline associated with menopause. One large study, which combined both cross-sectional and longitudinal data and used total body potassium levels as the most reliable current measure of body cell mass, showed a 1.2% decline in total body potassium levels per year for each of 3 years around menopause [3]. We refer to this age-related loss of skeletal muscle mass as sarcopenia (literally, lack of flesh) to describe a condition that has profound physiologic and clinical consequences and therefore greatly warrants further attention and study [4]. Poehlman and colleagues [2] have used a longitudinal study design to emphasize the accelerated loss of fat-free mass during menopause. Similar declines in the resting metabolic rate and reciprocal increases in fat mass were seen in women experiencing menopause and in those remaining premenopausal. The resting metabolic rate or basal metabolic rate is closely linked to fat-free mass because the muscle and viscera are the important metabolizing tissues in the body. Because the resting metabolic rate accounts for nearly two thirds of total caloric expenditure even in reasonably active people, fat-free mass or its loss is an important determinant of total energy requirements and appetite. Much research has been done to learn about osteopenia (the age-related loss of bone mass that may result in osteoporosis) and its clinical consequences, including increased risk for fracture. Much less attention has been paid to understanding the mechanism of sarcopenia. As shown by Poehlman and colleagues [2], this area is just as important quantitatively and has consequences that extend beyond the changes in energy metabolism to changes in variables such as strength, balance, tendency for falls, total exercise capacity (maximum oxygen consumption), efficiency of glucose disposition, and insulin sensitivity. Poehlman and coworkers [2] provide some basis for hypotheses about neuroimmunoendocrine factors that may regulate the maintenance of muscle mass or its loss with age. Although not measured in this study, the loss of estrogen production that occurs with menopause is associated with an accelerated loss of lean mass in perimenopausal women. It is well known that estrogen potentiates growth hormone secretion [5, 6]; the loss of this potentiation could be a factor in the loss of an important trophic effect on skeletal muscle. Another possibility is that estrogen modulates the activity of cytokines, leading to a more catabolic milieu. For example, production of interleukin-6 is inhibited by estradiol [7], and loss of estrogen could lead to greater interleukin-6 activity; this change may have catabolic consequences. Production of interleukin-1 differs between men and premenopausal women [8]: Women make more interleukin-1 than men, especially during the luteal phase of their menstrual cycle [9]. The production of interleukin-1 during the luteal phase parallels increases in resting energy expenditure, resulting in an increase in the energy intake necessary to maintain body composition. Interleukin-1 is not secreted in the luteal phase after menopause; however, because intake may not be accurately adjusted, the observed increase in fat could result. Such imprecision in appetite regulation has been documented in older persons [10]. A decline in physical activity, such as that shown by Poehlman and colleagues [2], could further contribute to a loss of lean mass and an increase in fat. Whatever the mechanisms involved in this nearly universal loss of lean muscle mass that increases with age and is accelerated by menopause, increasing evidence suggests that a readily accessible approach to prevention should be used more widely. Exercise is extremely important throughout life for women and men for various health reasons, but especially with regard to changes in body composition and muscle function. Resistance training especially targets the decrements in muscle mass and function typically seen in sedentary persons. Evidence now indicates that one is never too old to benefit from exercise; this is true even for frail institutionalized women as old as 100 years [11, 12]. When previously sedentary nonagenarians began a resistance training program for the lower extremities, Fiatarone and colleagues [11] showed by computed tomographic scans that the cross-sectional muscle area of the mid-thigh increased by 9% and that maximal muscle strength increased by 174% on average. Because increased muscle mass may be associated with greater insulin sensitivity, with skeletal muscle being the largest repository for glucose disposal, maintenance of lean body mass through exercise may also have other important health benefits. Poehlman and colleagues [2] did not explain why menopausal women had lower physical activity than women remaining premenopausal. Whatever the cause, this difference certainly contributed to the changes in body composition seen during menopause. As we focus more of our scientific attention on the phenomenon of sarcopenia and loss of muscle mass with age during menopause, we should begin to use one well-established remedy that is simple in concept, if not always easy to implement: greater physical activity and, particularly, progressive resistance training. The public health benefits of more widespread exercise, measured in terms of improved strength, mobility, and balance and delay of frailty and institutionalization, could be great and cost-efficient indeed.