The influence of age on low density lipoprotein metabolism: effects of cholestyramine treatment in young and old healthy male subjects

Objective, The plasma concentration of low density lipoproteins (LDL) increases with age, mainly as the result of a reduced clearance of LDL, Because the conversion of cholesterol to bile acids is reduced with age, we hypothesized that the response of plasma LDL to stimulation of bile acid production would be different in young and old subjects. Design, subjects and setting. Comparison of the response to cholestyramine treatment in two groups of normolipidaemic, normal weight males: seven young (23-34 years) and eight old (64-73 years), Outpatients at the metabolic ward of a university hospital given a standardized diet of natural type. Intervention. Cholestyramine was given 8 g b.i.d. for 3 weeks and continued during the second LDL turnover study. Main outcome measures, Kinetics of autologous radiolabelled LDL before and during treatment. Mean values of lipoprotein lipid levels obtained during the two turnover studies. Changes in LDL particle composition and LDL receptor affinity between the two study periods, Results, Both age groups responded with decreased levels of LDL cholesterol and apolipoprotein-B (apoB), the change being more pronounced in the old subjects, The LDL apoB fractional catabolic rate was increased by approximate to 11% in both groups, In contrast, there was a reduced ability in the old subjects to sustain their production rates for LDL apoB with resin therapy, resulting in a 23% reduction in LDL input. No effect on the apparent LDL apoB synthesis rate was observed in the young subjects, LDL particles isolated from cholestyramine-treated subjects were triglyceride-enriched and cholesterol-depleted, and showed a lowered affinity for the LDL receptor in tissue culture studies. Conclusions, The results demonstrate that stimulation of bile acid production by cholestyramine treatment decreases LDL cholesterol levels in both young and old subjects. This therapy increases LDL apoB elimination in both age groups, but reduction of apparent LDL apoB production is only seen in old subjects.