Research experience by the applicant in biochemistry as an undergraduate stimulated an interest in scientific inquiry which became focused on the aging process during internal medicine residency at the University of Michigan. This led to clinical training in geriatrics at Johns Hopkins and a research fellowship in the National Institute on Aging where the major areas of investigation involve the study of the effects of primary aging versus secondary age-related processes on hemodynamic and metabolic function. Receipt of this award will allow extension of the applicant's training in the area of metabolic research in gerontology. Dedicated research time in this enriched research environment will permit development of academic prowess and skills in biomedical research necessary for independent stature as a clinical investigator in gerontology. Hypertension (HTN), a major risk factor for vascular disease in the elderly, is associated with insulin resistance and hyperinsulinemia. This research determines role of physical inactivity, a lifestyle habit rather than a primary aging process per se, in the pathogenesis of HTN in the elderly. The hypothesis is that physical inactivity and the resultant decline in V02max and muscle mass in the elderly leads to insulin resistance which increases sympathetic nervous system activity (SNSA) and alters sodium balance to cause HTN. As a corollary, interventions which increase V02max (aerobic exercise, AE) and/or muscle mass (resistive training, RT) will reduce insulin resistance and SNSA to improve HTN. The research determines the relationship of Vo2max and muscle mass to insulin resistance, SNSA, sodium balance and BP in old men by : (a) comparing in vivo insulin sensitivity (euglycemic hyperinsulinemic clamps), insulin secretion.(hyperglycemic clamps), SNSA (NE kinetics) and sodium balance in HTN and normal men of comparable age and body mass index; and (b) assess the effects of 6-9 mo. AE or RT on glucose metabolism, SNSA and blood pressure in these men. Analyses of the cross-sectional (multivariate regression) and intervention (ANOVA, analysis of covariance, linear models) studies will determine the role of decreased physical activity in the pathogenesis of HTN and insulin resistance in the elderly. The results have implications for reducing morbidity and mortality from cardiac and cerebrovascular disease, thereby improving the survival and reducing socioeconomic costs of medical care for the elderly.
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