Sarcopenia is characterized by progressive, involuntary loss of skeletal muscle mass and muscle strength during old age. Magnetic Resonance Spectroscopy (MRS) provides information on muscle composition and muscle function that is difficult to obtain without resorting to invasive methods. This project will develop and apply 1H and 31p MRS methods to study changes in muscle composition and physiologic function that could be associated with sarcopenia.
The specific aims are: (1) to transfer 31p spectroscopy methods for studying muscle energy kinetics from the University of New Mexico (where the methods were developed) to Wake Forest University School of Medicine (WFUSM); (2) to develop proton (1H) spectroscopy methods for measuring extra- and intramyocellular lipid; and, (3) to apply these methods to selected samples of elderly study participants in New Mexico and to WFUSM patients with peripheral artery disease (PAD) and WFUSM healthy, sedentary controls, in order to collect preliminary data. These pilot data will be relevant to the following hypotheses: (a) muscle energy kinetics, as measured using 31p MRS, diminishes in sarcopenic muscle, and is associated with reduced muscle strength, reduced physical performance, low serum antioxidant vitamin status, decreased serum levels of hormones, and increased serum cytokines, controlling for age, gender, and physical activity; (b) the ratio of intra- to extracellular lipid, as measured by 1H MRS, increases in aged muscle and is associated with insulin resistance, decreased serum hormones, and increased plasma cytokines, controlling for gender, body fatness, and physical activity; (c) patients with PAD are significantly different from controls with regard to 31P and 1H MRS measures, mitochondrial DNA mutations, muscle fiber type, capillary density, and oxidative and glycolytic enzyme activities from muscle biopsies; and (d) 31P and 1H MRS measures in both PAD patients and healthy, sedentary controls are correlated with mitochondrial DNA mutations, muscle fiber type, capillary density, and oxidative and glycolytic enzyme activities from muscle biopsies. Because the presence of mitochondrial DNA injury has already been established in PAD patients, this study will provide an efficient validation of the indirect noninvasive MRS measurements of muscle mitochondrial dysfunction and composition. It will also provide preliminary data on whether PAD represents a potentially important pathway to sarcopenia.
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