The long term goal is to understand how nutritional factors influence muscle protein metabolism, and how these factors might influence the loss of muscle mass associated with old age. Three hypotheses will be examined: 1. That myofibrillar protein synthesis is proportional to protein intake at a constant energy intake; 2. That myofibrillar protein synthesis is proportional to energy intake at a constant protein intake; 3. That a high protein or a high energy diet stimulate myofibrillar protein synthesis in subjects engaged in a resistance exercise program. Subjects will be healthy men and women, 60-75 years old. In the first study they will be randomly assigned to consume one of the following diets for one week before the myofibrillar protein synthesis study: low protein (5% of energy), normal protein (15% of energy), or high protein (25% of energy). In the second study, subjects will be randomly assigned to receive one of the following diets for one week before the protein synthesis study: low energy (50% of weight-maintenance), normal energy (100% of weight-maintenance), high energy (150% of weight maintenance). In the third study, the high protein/normal energy, the high energy/normal protein, and the normal protein/normal energy diets will be given to subjects who are engaged in a resistance exercise program. Incorporation of the stable isotope L-[1-13C]leucine into myofibrillar proteins, isolated from muscle biopsies taken from the vastus lateralis muscle, will be determined to evaluate myofibrillar protein synthesis. Levels of the mRNAs that encode the most abundant myofibrillar proteins, myosin head chain and actin, will be determined in these biopsy samples to evaluate whether diet or exercise affects protein synthesis through pretranslational processes. Excretion of 3-methylhistidine will be used as an index of wholebody myofibrillar protein degradation. Because muscle fiber size is determined by the balance between protein synthesis and protein degradation, these studies will provide significant new information that could help to predict nutritional strategies to optimize muscle mass in old age.
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