Linking age-related changes in skeletal muscle morphology with metabolism and disease.

摘要

The objective of this thesis was to employ novel methodologies to describe age-related changes in skeletal muscle (SM) morphology (i.e., mass and composition), and, to link these changes to alterations in metabolism and disease. The first study examined the relationship between age, total, and regional SM measured by magnetic resonance imaging (MRI) in a heterogeneous sample of 468 men and women. SM mass relative to body weight was reduced starting in the third decade; however, a noticeable decrease in absolute SM mass was not observed until ∼45 years of age. The decrease in SM mass was primarily attributed to a decrease in lower body SM.; In the second study a method for estimating SM mass using bioelectrical impedance analysis (BIA) was developed in a cohort of 388 adults. The R 2 and standard error of the estimate for predicting MRI-measured whole body SM mass with BIA were 0.86 and 2.7 kg (9%), respectively. The results of this study provide, for the first time, a clinically useful tool for measurement of SM in Caucasians, Hispanics, and African-Americans varying widely in age and adiposity.; The development of a BIA equation for rapid and accurate determination of SM set the stage for the third study wherein we established the prevalence of sarcopenia (low relative SM mass) and determined whether sarcopenia is related to functional impairment in older adults. The participants consisted of a nationally representative sample of 14,818 adults. The prevalence of class I (moderate) and class II (severe) sarcopenia in older (≥60 years) men were 45% and 7%, respectively. The corresponding values in older women were 59% and 10%. The likelihood of functional impairment and disability was approximately twofold greater in the older men and threefold greater in the older women with class II sarcopenia by comparison to the older men and women with a normal SM mass, respectively. These observations provide strong support for the prevailing view that sarcopenia is a common occurrence and an important cause of morbidity in older persons.; In the final study the influence of aging and physical activity on the relationship between intramyocellular lipid (IMCL) content and insulin sensitivity was examined. Insulin sensitivity was assessed by the hyperinsulinemic euglycemic clamp and a novel method, proton magnetic resonance spectroscopy, was employed to measure IMCL. IMCL levels were 35% higher in lean older women by comparison to lean young women. However, the older women did not have a reduced insulin sensitivity, which indicates that increased IMCL is not a mediator of insulin resistance in older persons. After controlling for the residual effects of the last exercise session, IMCL and insulin sensitivity values were similar in the sedentary and moderately trained women.