Influence of age on the metabolism of plasma low density lipoproteins in healthy males

Abstract

The plasma concentration of the atherogenic low density lipoproteins (LDL) increases with age. To clarify the mechanism of this change, we studied the kinetics of autologous 125I-LDL apolipoprotein B (apo B) in 41 normolipidemic, nonobese healthy males. For comparison, they were divided into three age groups: young, 21-39 yr (n = 18), middle-aged, 40-59 yr (n = 11), and old, 60-80 yr (n = 12). The levels of plasma LDL cholesterol and LDL apo B increased from respectively 3.4±0.1 (SEM) mmol/liter and 86±2 mg/dl in the young to 4.1±0.1 mmol/liter and 95±3 mg/dl in the old (P < 0.01), and this increase was linked to a progressively decreased (r = -0.38, P < 0.02) fractional catabolic rate of LDL apo B (0.348±0.010 pools per day in the young vs. 0.296±0.009 pools per day in the old, P < 0.01). The production rate of LDL apo B did not differ significantly between the groups. The reduced fractional catabolic rate of LDL apo B in the old was not associated with a decrease in binding affinity of the LDL particle to its receptor, as judged from its ability to compete for 125I-LDL fibroblast binding. When hepatic LDL receptor expression was stimulated by cholestyramine treatment in six old males, their LDL apo B fractional catabolic rate increased to the levels observed in the young subjects. We conclude that the increase in LDL which normally occurs with age is explained by a reduced capacity for its removal, and hypothesize that this is mediated via a reduced hepatic LDL receptor expression.