EFFECT OF AGING ON CHOLESTEROL 7-ALPHA-HYDROXYLATION IN HUMANS

In order to investigate the alterations of bile acid synthesis in agin g, we studied the rates of cholesterol 7alpha-hydroxylation, the rate- limiting step, in 28 patients of different ages (34-83 years old, 14 b elow and 14 above the age of 65) of both sexes. Hydroxylation rates we re determined by tritium release assay after an intravenous bolus of [ 7alpha-H-3]cholesterol. Cholesterol 7alpha-hydroxylation was significa ntly decreased in the older age group, compared to middle-aged subject s, both in males and females; moreover, a significant inverse correlat ion between hydroxylation rates and age was found in the whole sample (r = -0.56; P < 0.01) and in females, but not in males. The percent co ncentration of deoxycholic acid in plasma (determined by gas-liquid ch romatography) was increased in older subjects. Plasma cholesterol and triglyceride levels were not related with age even though triglyceride concentrations tended to be lower in the older age group. Triglycerid e, but not cholesterol levels, were directly correlated with hydroxyla tion rates (r = 0.45, P < 0.05). After cholestyramine treatment (8-12 g/day for 4 weeks) a sharp increase in 7alpha-hydroxylation rates was observed in three elderly patients, accompanied by reduced levels of d ihydroxylated bile acids. Our data are consistent with a reduced rate of conversion of cholesterol to bile acids with aging, particularly in females, and suggest a coordinate reduction of triglyceride productio n. Alterations of the quantitative and/or qualitative pattern of the b ile acid pool recirculating to the liver may be responsible, at least in part, for the changes observed.