. 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.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Scientist Development Award - Research & Training (K01)
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Study Section
National Institute on Aging Initial Review Group (NIA)
Program Officer
Rossi, Winifred K
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University of Pittsburgh
Internal Medicine/Medicine
Schools of Medicine
United States
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Menshikova, Elizabeth V; Ritov, Vladimir B; Fairfull, Liane et al. (2006) Effects of exercise on mitochondrial content and function in aging human skeletal muscle. J Gerontol A Biol Sci Med Sci 61:534-40
Goodpaster, Bret H; Krishnaswami, Shanthi; Harris, Tamara B et al. (2005) Obesity, regional body fat distribution, and the metabolic syndrome in older men and women. Arch Intern Med 165:777-83
Pruchnic, Ryan; Katsiaras, Andreas; He, Jing et al. (2004) Exercise training increases intramyocellular lipid and oxidative capacity in older adults. Am J Physiol Endocrinol Metab 287:E857-62
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Goodpaster, Bret H; Katsiaras, Andreas; Kelley, David E (2003) Enhanced fat oxidation through physical activity is associated with improvements in insulin sensitivity in obesity. Diabetes 52:2191-7
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Goodpaster, Bret H; Wolfe, Robert R; Kelley, David E (2002) Effects of obesity on substrate utilization during exercise. Obes Res 10:575-84
Goodpaster, B H; Carlson, C L; Visser, M et al. (2001) Attenuation of skeletal muscle and strength in the elderly: The Health ABC Study. J Appl Physiol 90:2157-65

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