With advancing age the decline in physical conditioning, indexed as maximal aerobic capacity (V02 max), renders older people less able to respond to stresses, especially disease. Older people are prone to develop glucose intolerance, hyperlipidemia and obesity, metabolic risk factors for atherosclerosis. This decline in metabolic function may not be solely due to biological aging, but may be related to the declining V02 max and increasing body fat that accompany aging. To study the mechanisms by which physical conditioning affects lipid and glucose metabolism and body composition, 55-75 yr old men with a broad range of V02 max will be screened for coronary and metabolic disease by medical history and exam, blood tests, exercise electrocardiography with thallium scans, glucose tolerance tests and lipid profiles to exclude silent ischemia, diabetes and dyslipoproteinemia. Ninety disease-free men will be selected for study: 70 will be lean and less than 20% body fat with wide range of V02 max (20-60 ml/kg/min) and 20 will be moderately obese (25-30% body fat) with V02 max 20-35 ml/kg/min. Studies of glucose and lipoprotein metabolism will determine: (a) Role of pancreatic beta cell (insulin secretion) and peripheral tissues (insulin action) in regulation of glucose homeostasis by measuring beta cell sensitivity to glucose (hyperglycemic clamp) and whole body and hepatic sensitivity to insulin (euglycemic clamp); and (b) Role of lipoprotein lipase and hepatic lipase in the regulation of chylomicron and very low density lipoprotein (VLDL) triglyceride (TG) and high density lipoprotein (HDL) subspecies metabolism by measuring postprandial (oral fat) lipoprotein-TG responses and their relationship to HDL, VLDL-TG turnover and postheparin lipases. Longitudinal studies of conditioning and deconditioning will determine mechanisms by which differences in physical conditioning cause diversity in glucose and lipoprotein metabolism and body composition by converging subjects to comparable V02 max. Thus, master athletes (V02 max: 50-60 ml/kg/min) will be deconditioned, lean men conditioned and moderately obese men conditioned and weight reduced towards the V02 max and % body fat of conditioned (V02 max:40-49) seniors. The metabolic effects of the interventions will be remeasured. It is our hypothesis that metabolic function and body composition are not fixed and will vary with changes in physical conditioning status. These results will differentiate effects of primary from those of secondary aging and determine the mechanisms by which change in physical conditioning affects metabolic function.
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