Doctor of Philosophy

dissertationIntramuscular adipose tissue (IMAT) is an important negative predictor of muscle and mobility function in older adults. While IMAT has been theorized to increase with aging, more recent evidence suggests that IMAT may be a byproduct of inactivity rather than aging per se. The mechanism of IMAT's influence on muscle and mobility function is unknown but similar to the negative consequences attributed to other ectopic fat depots, may involve an inflammatory pathway. In order to clarify if IMAT is an obligatory consequence of age or if it is related to inactivity, the primary aim of this study was to compare IMAT, muscle and mobility function, and muscular inflammation in age and BMI matched older frail and nonfrail adults. A secondary aim was to examine the relationship of IMAT and visceral adipose tissue (VAT), muscular inflammation, muscle function and mobility function in a subgroup of older adults. Two groups of older nonobese adults were recruited. A sedentary frail group was classified as at least moderately frail with modified physical performance test scores of 32. Magnetic resonance imaging (MRI) was used to determine mean cross sectional area of thigh IMAT and VAT. Maximal voluntary isometric contractions were used to determine muscle function, and 6 minute walk and stair ascent time were used to determine mobility function. A sub group of participants from both groups who were free from disease and medications known to influence inflammation underwent percutaneous muscle biopsies iv of the vastus lateralis. Western blot and real time polymerase chain reaction were used to determined local muscular expression of mRNA and protein for the proinflammatory cytokines interleukin 6 (IL-6) and tumor necrosis alpha (TNF-a). We found significant differences in IMAT, and IL-6 mRNA and protein expression between frail and nonfrail adults. We also found significant correlations between IMAT, VAT, IL-6, and muscle and mobility function. These findings suggest that IMAT is a product of inactivity and disease rather then aging alone and provide a potential mechanistic link between increased IMAT and decreased muscle and mobility function in older adults