Interaction of aging and dietary fat in the regulation of low density lipoprotein transport in the hamster

These studies were undertaken to examine the effect of aging on low density lipoprotein (LDL) metabolism in the male hamster. When the hamsters were maintained on a low-cholesterol, low-triglyceride diet, rates of LDL transport in the various tissues of the body and plasma LDL-cholesterol concentrations remained constant over the entire life span (1-24 months) of the hamster. In contrast, rates of the novo cholesterol synthesis fell 50-97% in the various tissues of the body during the transition from rapid body growth in the young animal to the stable adult size. Thus, changes in tissue requirements for cholesterol over the life span of these animals were met by an appropiate adjustment in the rate of novo synthesis rather than by alterations in LDL transport. When animals were fed a diet enriched in cholesterol and saturated triglycerides, rates of LDL production increased, total body LDL receptor activity was suppressed, and plasma LDL-cholesterol levels rose. Older animals, however, were not more susceptible than young animals to the detrimental effects of these dietary fats. These studies support the view that aging per se has no effect on LDL transport by the liver or other tissues. Rather, the progressive rise in plasma LDL-cholesterol levels seen in Western man is likely due to the consumption of a diet enriched in cholesterol and satured triglyceride which increases the LDL-cholesterol production rate and suppresses receptor-dependent LDL transport.