Aging is associated with changes in lipoprotein metabolism which may predisopose the elderly to increased morbidity and mortality. The well-known in cholesterol and low density lipoprotein (LDL) levels into the 6th decade predispose to atherosclerosis and coronary artery disease. Hypocholesterol and decreased levels of LDL may occur after the 6th decade, associated with cachexia and increased mortality. Whether these changes in lipoprotein metabolism result from the primary process of aging or result from undetected disease or changes in lifestyle variables such as physical activity, diet, or body composition, is the basic questions addressed by this proposal. To study the mechanisms by which physical conditioning status body composition affect lipoprotein metabolism in the elderly, 60-90 healthy men aged 55-75 will be rigorously screened for coronary and metabolic disease, selected for study, and grouped by conditioning status (maximum oxygen consumption) and body composition (percent body fat). These groups cross-sectionally at baseline. To determine effects of changes in conditioning status, the lean athletic group will be detrained and the composition, the unconditioned overweight will undergo weight loss through a combination of dietary reduction and exercise, and the unconditioned underweight will undergo weight gain through dietary supplementation. In all groups, fasting very low density (VLDL), LDL, and high density (HDL) lipoprotein and apolipoprotein A1 and B levels will be measured. Following a standard oral fat meal, postprandial chylomicron, VLDL, LDL, HDL, and apolipoprotein B48 levels will be measured. Apolipoprotein E phenotype and lipoprotein lipase, hepatic lipase, and intravenous fat tolerance will be measured to assess these regulators of triglyceride clearance. Additionally, cell proliferation and cholesterol and sphingomyelin synthesis will be measured in fibroblasts and lymphocytes in defined media containing isolated lipoproteins from the same subjects. The results of these investigations will identify the effects of altering physical conditioning status or body composition on levels of individual lipoproteins and apolipoproteins and cell replication and membrane synthesis. This will give insight into the mechanisms by which secondary aging processes modulate lipoprotein metabolism in the early, and can, themselves be modulated by changing lifestyle.
Showing the most recent 10 out of 77 publications
