S. Ericsson et al., THE INFLUENCE OF AGE ON LOW-DENSITY-LIPOPROTEIN METABOLISM - EFFECTS OF CHOLESTYRAMINE TREATMENT IN YOUNG AND OLD HEALTHY MALE-SUBJECTS, Journal of internal medicine, 242(4), 1997, pp. 329-337
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. De
sign, subjects and setting. Comparison of the response to cholestyrami
ne treatment in two groups of normolipidaemic, normal weight males: se
ven young (23-34 years) and eight old (64-73 years), Outpatients at th
e 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 outcom
e measures, Kinetics of autologous radiolabelled LDL before and during
treatment. Mean values of lipoprotein lipid levels obtained during th
e two turnover studies. Changes in LDL particle composition and LDL re
ceptor affinity between the two study periods, Results, Both age group
s responded with decreased levels of LDL cholesterol and apolipoprotei
n-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 s
ubjects to sustain their production rates for LDL apoB with resin ther
apy, resulting in a 23% reduction in LDL input. No effect on the appar
ent LDL apoB synthesis rate was observed in the young subjects, LDL pa
rticles isolated from cholestyramine-treated subjects were triglycerid
e-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 subj
ects. This therapy increases LDL apoB elimination in both age groups,
but reduction of apparent LDL apoB production is only seen in old subj
ects.