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.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
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Special Emphasis Panel (ZRG4-GRM (01))
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University of Rochester
Internal Medicine/Medicine
Schools of Dentistry
United States
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Welle, Stephen (2002) Cellular and molecular basis of age-related sarcopenia. Can J Appl Physiol 27:19-41
Welle, Stephen; Bhatt, Kirti; Shah, Bharati et al. (2002) Insulin-like growth factor-1 and myostatin mRNA expression in muscle: comparison between 62-77 and 21-31 yr old men. Exp Gerontol 37:833-9
Welle, S; Brooks, A; Thornton, C A (2001) Senescence-related changes in gene expression in muscle: similarities and differences between mice and men. Physiol Genomics 5:67-73
Welle, S; Bhatt, K; Thornton, C A (2000) High-abundance mRNAs in human muscle: comparison between young and old. J Appl Physiol 89:297-304
Welle, S; Bhatt, K; Thornton, C A (1999) Stimulation of myofibrillar synthesis by exercise is mediated by more efficient translation of mRNA. J Appl Physiol 86:1220-5
Welle, S; Bhatt, K; Thornton, C A (1999) Inventory of high-abundance mRNAs in skeletal muscle of normal men. Genome Res 9:506-13
Welle, S (1998) Growth hormone and insulin-like growth factor-I as anabolic agents. Curr Opin Clin Nutr Metab Care 1:257-62
Welle, S; Thornton, C A (1998) High-protein meals do not enhance myofibrillar synthesis after resistance exercise in 62- to 75-yr-old men and women. Am J Physiol 274:E677-83
Welle, S; Thornton, C; Bhatt, K et al. (1997) Expression of elongation factor-1 alpha and S1 in young and old human skeletal muscle. J Gerontol A Biol Sci Med Sci 52:B235-9
Welle, S; Thornton, C (1997) Insulin-like growth factor-I, actin, and myosin heavy chain messenger RNAs in skeletal muscle after an injection of growth hormone in subjects over 60 years old. J Endocrinol 155:93-7

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