. This applicant requests support for an additional period of training in methodologies important to develop his academic research career in skeletal muscle metabolism in aging and disease. The overall research aim of this award is to examine the hypothesis that aging results in an increased fat content within skeletal muscle which may potentially have important implications with regard to insulin resistance, substrate metabolism and functional capacity. In this context the candidate will receive training from more persons who will mentor him in developing and applying techniques to study the relationships of muscle composition, substrate utilization, exercise and aging. These muscle histology, magnetic resonance imaging (MRI) and stable isotope methodologies are for advancing the candidate toward becoming an independent investigator in muscle structure, biochemistry, and physiology in aging, obesity, disease, and exercise. This project intends to develop and utilize MRI methodology to quantify the fat content of muscle. The use of echo planar (EP) MRI will provide a noninvasive means with no ionizing radiation to precisely quantify adipose tissue content of muscle by analyzing water suppressed and fat images of the thigh. This technique will be compared to CT-determined muscle composition and histochemical and biochemical methods for determining intramuscular fat content. Aging may contribute to decreased metabolic function, ie, insulin resistance. Using the glucose clamp technique and stable isotope methodology to measure 2H-glucose turnover, this project will investigate the relationship of an increased fat content within aging skeletal muscle to insulin resistance. Fuel use during physical activity could be altered in older persons, leading to an increased fat deposition within muscle, and thus exacerbating the metabolic complications potentially associated with an increased fat storage within muscle. This project intends to examine the hypothesis that in older individuals, fat oxidation is impaired during exercise. A corollary is to use stable isotope methods to characterize utilization of intramuscular triglyceride as well as plasma FFA during exercise in older compared to younger individuals. It is hypothesized that older persons oxidize less FFA from intramuscular sources which is presumed to lead to further increases in fat storage within muscle. This project will also examine the hypothesis that aerobic exercise training in older persons decreases fat content of muscle as determined by MRI and has a beneficial effect on muscle metabolism to enhance utilization of energy from lipid sources during exercise.
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