Age-related changes in the regulation of cholesterol metabolism in rats

Activities of the hepatic cholesterol synthetic system including initial steps of the pathway and cholesterol 7 alpha-hydroxylase were all lower in adult (8 to 9-month-old) rats than in young (5 week-old) rats. The extent of diurnal fluctuation of 3-hydroxy-3-methylglutaryl coenzyme A reductase was, however, apparently greater in adult animals. When the cholesterol-enriched diet was fed to rats for 1 day, the extent of the depression of the cholesterogenic enzymes was dependent on age of animals. The enzyme activities rapidly increased on refeeding a cholesterol-free diet after the cholesterol challenge. In young rats the activity of cholesterol 7 alpha-hydroxylase exhibited a pattern inverse to that of HMG-CoA reductase whereas in adult rats it increased continuously during the entire experimental period. Cholesterol and triglyceride accumulated in the liver of adult animals, and their response to dietary cholesterol also depended on the age of the animals. The results indicate a specific modification of the cholesterol homeostatic mechanism with age.