Body composition of all too many older women is characterized by excess body weight and fat mass and reduced fat-free mass (FFM) and muscle mass. Older women also typically have decreased total energy expenditure due to a lowered resting metabolic rate (RMR) and diminished physical activity. These factors have contributed to an increased risk for many age-related disorders, including hypertension, diabetes, heart disease, and impaired strength and mobility. Many of these older women may desire and attempt to reduce their body weight. However, it is increasingly apparent that dieting alone may result in a decline in physical function and health status, including further reductions in muscle mass and strength, and increased risk for mobility disability. In young women, diet-induced weight loss also changes protein and energy metabolism, including a more negative nitrogen balance and a reduction in RMR. Resistance training (RT) has been shown to increase muscle strength and mass, enhance nitrogen retention and protein utilization, increase RMR and total energy requirements, and improve physical functional status in older people. Many of these positive results also occur with RT with weight loss in overweight young women. The combined influences of diet-induced weight loss and RT on protein and energy metabolism are largely unstudied in older women. This R-29 FIRST award proposal will test the hypotheses that diet-induced weight loss in older women will result in significant losses of FFM and skeletal muscle mass, and that these losses will adversely effect protein and energy metabolism and reduce muscle strength and muscle function. The hypotheses that RT, with or without an energy restriction diet, will preserve FFM and muscle mass, increase nitrogen retention and protein metabolism, and preserve RMR, will also be tested. Nitrogen balance techniques will be used to assess protein balance, and the tracers 1-[13C]-leucine and L-[ring2D5]-phenylalanine will be used to assess whole-body and skeletal muscle protein metabolism, respectively. RMR will be measured by indirect calorimetry. Body composition and muscle strength, function, and size will be quantified. Strict dietary control will be maintained by providing protein- and energy-defined menus using the General Clinical Research Center at Noll Laboratory. This study will provide new and important information about effective therapies for the treatment of obesity and prevention of sarcopenia in older women, a segment of the population at risk to physical frailty.
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