Claude D. Pepper Older Americans Independence Center (OAIC) 1999 - 2004
IDS-1 - Interaction of Nutrition and Exercise on Muscle
Robert R. Wolfe, Ph.D., Project Leader
Dr. Wolfe is internationally recognized for his work on muscle metabolism, but has only recently turned his attention to aging muscle. In their previous research, Dr. Wolfe and his colleagues have shown anabolic responses of muscle protein to amino acid supplements, resistance exercise, and aerobic exercise in normal young volunteers. They have more recently demonstrated that older individuals respond with anabolic effects to a nutritional supplement containing essential amino acids. It has previously been shown that resistance training in elderly individuals can improve strength and function, and that those improvements are related to an increase in muscle protein synthesis. However, the response of muscle protein metabolism in older individuals to aerobic exercise has not previously been investigated, nor has the interactive effects on muscle protein metabolism of any type of exercise and a nutritional supplement. It is therefore the general goal of this project to determine in older individuals the independent effects of an amino acid supplement, aerobic exercise and resistance exercise on muscle protein metabolism, and also to determine if prior exercise of either type amplifies the anabolic response to a nutritional supplement.
We will use stable isotope tracer methodology, arterial-venous sampling across the legs, and muscle biopsies to quantify rates of muscle protein synthesis and breakdown. These studies will form the basis for developing an intervention study to evaluate the optimal approach to improving muscle mass and function in free-living and institutionalized older individuals.
IDS-2 - Interaction of Nutrition and Anabolic Steriod Hormones in Promoting Muscle Function in Older Men and Women
Randall Urban, M.D., Project Leader
FAX: (409) 772-8709
Dr. Urban and others have shown that short- and long-term administration of testosterone increases muscle protein synthesis and improves muscle function (strength) in older men. They have also shown that testosterone increases intramuscular IGF-I gene expression, which may be the mechanism for the increase in protein synthesis. We now wish to build on these findings, exploring the interaction of an oral androgen, oxandrolone, and nutritional supplementation on muscle function. Central to this effort is to investigate physiologic and molecular mechanisms and to relate these to outcomes such as muscle strength and size and function. Specifically, we are conducting a randomized prospective trial of the effects of oxandralone and supplementation with essential amino acids for 3 months on muscle function in older men and women. There are four experimental groups:
- Placebo control
- Amino acid supplementation
- Amino acid supplementation plus oxandralon
Outcome measurements include:
- Muscle protein synthesis, breakdown, and amino acid transport
- Gene expression of the intramuscular IGF-I system and androgen receptor
- Muscle size and strength
- Body composition
Both IDS-1 and IDS-2 are closely linked to all pilot proposals in two ways. First, the pilot investigators obtain muscle tissue (or muscle RNA via the Cell Biology Core) from IDS-2 for their investigations. Second, the pilot studies develop assays that allow us to ask more sophisticated questions about the precise mechanisms whereby supplementation with essential amino acids, exercise, and anabolic hormones result in increased muscle functioning.