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

作者：Bertolotti Marco^*; Mussi Chiara; Pellegrini Elisa; Magni Alessandro; Del Puppo Marina; Ognibene Silvia; Carulli Lucia; Anzivino Claudia; Baldelli Enrica; Loria Paola; Carulli Nicola

来源：Clinical Interventions in Aging, 2014, 9: 425-432.

DOI：10.2147/CIA.S57714

• aging
• cholesterol metabolism
• cholesterol synthesis
• gallstone disease
• cardiovascular risk

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. %26lt;br%26gt;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 7 alpha-hydroxy-4-cholesten-3-one (degradation to bile acids). %26lt;br%26gt;Results: A significant direct correlation was detected between age and cholesterol levels (r=0.34, P%26lt;0.01). The lathosterol/cholesterol ratio was lower in older age quartiles (P%26lt;0.05 by analysis of variance), with an inverse correlation between the lathosterol/cholesterol ratio and age (r=-0.32, P%26lt;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 7 alpha-hydroxy-4-cholesten-3-one were not correlated with age. %26lt;br%26gt;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.

• 出版日期2014