Age-associated alterations in cholesterol homeostasis: evidence from a cross-sectional study in a Northern Italy population

Abstract

Background: The modifications of cholesterol metabolism associated with aging are ill-defined. The objective of this study was to define age-associated alterations of the different metabolic pathways controlling cholesterol homeostasis by analyzing circulating sterols.

Methods: We analyzed serum samples collected from 201 adult (75 male, 126 female) subjects within the epidemiological MICOL study (Multicentrica Italiana Colelitiasi). The age range was 38-79 years; 103 had evidence of gallstones. The concentrations of the different sterols, recognized as markers of the main pathways of cholesterol homeostasis, were analyzed by gas chromatography-mass spectrometry, including lathosterol (synthesis), campesterol and sitosterol (absorption), and 7α-hydroxy-4-cholesten-3-one (degradation to bile acids).

Results: A significant direct correlation was detected between age and cholesterol levels (r =0.34, P<0.01). The lathosterol/cholesterol ratio was lower in older age quartiles (P<0.05 by analysis of variance), with an inverse correlation between the lathosterol/cholesterol ratio and age (r=-0.32, P<0.01). Such correlation was particularly evident in females. The campesterol/cholesterol and sitosterol/cholesterol ratios were inversely correlated with aging in control, but not in gallstone patients. The levels of 7α-hydroxy-4-cholesten-3-one were not correlated with age.

Conclusion: These data show a reduction of cholesterol synthesis with aging which is associated with increased circulating cholesterol levels. The finding might be related to a reduced metabolic need for cholesterol in advancing age, leading to a downregulation of the main mechanisms of cholesterol intake in the liver. A different age-related behavior was observed in gallstone-free versus gallstone patients regarding cholesterol absorption. The possible implications in terms of the pharmacological management of hypercholesterolemia in the elderly remain to be defined.

Keywords: aging; cardiovascular risk; cholesterol metabolism; cholesterol synthesis; gallstone disease.

Figure 1

Correlation between serum cholesterol levels and age. Notes: Individual data points are shown for 201 subjects; r=0.34; P<0.01, linear regression analysis.

Figure 2

Correlation between serum lathosterol to cholesterol ratio, a marker of cholesterol synthesis, and age. (A) Individual data points are shown for all subjects (n=201) of the studied cohort; r=−0.32; P<0.01, linear regression analysis; (B) data points are shown for gallstone-free subjects (n=98); r=−0.48; P<0.01, linear regression analysis; (C) data points are shown for gallstone patients (n=103); r=−0.28; P<0.01, linear regression analysis.

Figure 3

Correlation between serum levels of 7α-hydroxy-4-cholesten-3-one, a marker of cholesterol degradation to bile acids, and age. Note: Individual data points are shown for 201 subjects; r=−0.005; P>0.1.

Figure 4

Correlation between serum campesterol-to-cholesterol ratio, a marker of cholesterol absorption, and age. (A) Individual data points are shown for gallstone-free subjects (n=98); r=−0.23; P<0.05, linear regression analysis; (B) data points are shown for gallstone patients (n=103); r=−0.07; P>0.1.