PATHOGENESIS OF SARCOPENIA AND METABOLIC CHANGE IN AGING

Sarcopenia is a major public health problem among the rapidly elderly population expanding elderly population in our society. Disabilities directly related to muscle weakness, and indirectly related to changes in body composition and metabolic dysfunctions, are causing a staggering toll in disability and health care costs. Osteopenia occurs almost simultaneously with sarcopenia in the elderly population and muscle weakness increases the risk for falls and, therefore, fractures. Although these issues have been separately addressed in several studies, an integrated investigational approach to better understand the pathogenesis of sarcopenia and other age-related metabolic abnormalities and to investigate the potential role of androgens have not been undertaken in a comprehensive manner. The program contains four independent research programs, each representing different research disciplines, and four separate cores supporting the four projects. The main focus on the project is to determine the effect of the replacement of testosterone in elderly men and DHEA in elderly men and women and to compare these effects with placebo treatment over a two-year period. Project 1, "Effect of Androgen Replacement on Muscle Metabolism" will specifically determine whether these interventions have a different effect on size and quality of muscle in terms of strength and metabolic functions. Project 2, "Effect of Androgen Replacement on Bone Metabolism," will determine the effects of this intervention on bone mineral density and markers of bone turnover. Project 3, "The Effect of Androgen Replacement on Carbohydrate Metabolism," will determine whether the age-associated decrease in circulating androgens contributes to the alterations in carbohydrate metabolism that are commonly observed in the elderly and on insulin action, insulin secretion, and glucose effectiveness. Project 4, "Effect of Androgen Replacement on Fat Metabolism" will determine whether changes in fat distribution that occur with aging could result from differences in regional fatty acid uptake and systemic fatty acid kinetics, and whether these determinants of fat distribution are altered by the interventions. The data emerging from these studies will be integrated to determine the intervention of sarcopenia with other metabolic change and hopefully will contribute to a better understanding of the relationship between sarcopenia, hormonal changes, and many associated metabolic dysfunctions of muscle, bone, carbohydrate and fat metabolism. This study will hopefully form the scientific basis for future trials of androgen replacement in the elderly.