Effect of aging on cholesterol 7 alpha-hydroxylation in humans

In order to investigate the alterations of bile acid synthesis in aging, we studied the rates of cholesterol 7 alpha-hydroxylation, the rate-limiting step, in 28 patients of different ages (34-83 years old, 14 below and 14 above the age of 65) of both sexes. Hydroxylation rates were determined by tritium release assay after an intravenous bolus of [7 alpha-3H]cholesterol. Cholesterol 7 alpha-hydroxylation was significantly decreased in the older age group, compared to middle-aged subjects, both in males and females; moreover, a significant inverse correlation 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 concentration of deoxycholic acid in plasma (determined by gas-liquid chromatography) 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. Triglyceride, but not cholesterol levels, were directly correlated with hydroxylation rates (r = 0.45, P < 0.05). After cholestyramine treatment (8-12 g/day for 4 weeks) a sharp increase in 7 alpha-hydroxylation rates was observed in three elderly patients, accompanied by reduced levels of dihydroxylated 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 production. Alterations of the quantitative and/or qualitative pattern of the bile acid pool recirculating to the liver may be responsible, at least in part, for the changes observed.