ENERGY BALANCE AND INSULIN SENSITIVITY

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Dietary restriction (DR) consistently slows the rate of aging, while reducing the incidence and delaying the onset of age-related disease in nonprimate species. The goal of this program is to determine the effects of DR on aging and disease in rhesus monkeys. This component research project is designed to evaluate the impact on DR on the regulation of metabolism during aging from an integrative, physiologic standpoint. Body composition and distribution of body fat will be measured and related to insulin sensitivity and to insulin and glucose levels. The relationship on insulin levels to metabolic rate will be assessed. The following hypotheses will be tested: 1) DR will result in reductions in body weight, body fat and lean body mass, followed by stabilization at lower levels. These changes will be accompanied by sustained alternations in both the level and efficiency of energy utilization. 2) DR-association changes in glucoregulation and metabolic rate represent fundamental aging processes that are at least partially independent of changes in body composition, and consequently will be associated with other measures of biologic aging. In this context, elucidating the effects of aging and DR on glucose, via nonenzymatic glycosylation of proteins and DNA, is a general mediator of age-related change. This project will also probe the cellular mechanisms of increased insulin sensitivity with DR using studies of the GLUT-4 glucose transporter levels in skeletal muscle. Improved understanding of the hyperinsulinemia and elevated glucose levels characteristic of middle age is important, because these conditions are associated with a greater risk for many age-related diseases, including hypertension, cardiovascular disease, cerebrovascular disease, peripheral vascular disease, glaucoma, cataract, and nephropathy.