Aging is associated with a decrease in metabolic function which increases the likelihood of hyperlipidemia and glucose intolerance. In addition, cardiac reserve function (quantified as maximal aerobic capacity, VO2 max) declines with advancing age. These functional changes increase risk for coronary artery disease (CAD). The basic hypothesis of this proposal is that declines in metabolic function are not solely due to primary biological aging but occur predominantly due to secondary processes such as physical inactivity, obesity, and chronic disease. To determine the independent effects of physical activity on lipoprotein and glucose metabolism in older men, the other secondary processes must be controlled. Men of comparable age (60-75 yrs) and percent body fat (determined by hydrodensitometry) will be screened for overt and chronic disease. Occult CAD will be excluded by exercise stress tests and thallium scans. Metabolic dysfunction will be screened by glucose tolerance tests and lipoprotein profiles. Healthy, lean (less than 21% body fat), sedentary (VO2 max: 20-30 ml/kg/min) and highly conditioned (V02 max: 50-60 ml/kg/min) men will be selected for study. The regulation of lipoprotein metabolism will be determined by measuring fasted and postprandial (oral fat meal) levels of lipoprotein (VLDL, LDL, HDL) lipids and HDL subspecies, lipoprotein lipase and hepatic lipase activities, and VLDL triglyceride kinetics. The mechanisms regulating glucose metabolism will be determined by measuring insulin sensitivity and secretion and hepatic glucose production using the hyperglycemic and euglycemic clamp with radioisotope tracer studies. The effects of change in physical conditioning status, (defined by change in V02 max), on metabolic function will be assessed by implementing an aerobic exercise training program for the sedentary subjects and deconditioning the physically active men. The baseline metabolic testing will then be repeated. Analysis of results by paired t tests and regression analysis will differentiate between effects of physical deconditioning vs primary aging and determine the mechanisms by which altered conditioning status effects glucose and lipoprotein metabolism in older men. This may have important medical and socioeconomic implications for the prevention of CAD in this population.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Clinical Investigator Award (CIA) (K08)
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Special Emphasis Panel (GER)
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Johns Hopkins University
Schools of Medicine
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