Objectives: The modifications of cholesterol metabolism which associate with aging are ill-defined. The objective of this study is to define aging-associated alterations of the different metabolic pathways controlling cholesterol homeostasis by analysis of circulating levels of hydroxylated sterols.Methods: We analyzed serum samples from 123 adult subjects (45 male, 78 female, age range 38-78) from the epidemiological M.I.COL. study (Multicentrica Italiana Colelitiasi). The concentrations of the different hydroxysterols, recognized as markers of the main metabolic pathways of cholesterol homeostasis, were determined: synthesis (lathosterol), absorption (campesterol and sitosterol), degradation to bile acids (7alpha-hydroxy-4-cholesten-3-one). Analysis was performed by gas-chromatography - mass spectrometry.Results: a significant correlation was detected between age and cholesterol levels. The lathosterol/cholesterol ratio (an index of cholesterol synthesis) was lower in older (age > 65), compared to younger subjects (102\uf0b139 vs 126\uf0b162 microg/100 microg cholesterol; P < 0.05, t test for independent data). A significant inverse correlation was present between the lathosterol/cholesterol ratio and age. The remaining markers did not show significant modifications with aging, even if a trend toward a reduction of cholesterol markers was present.Conclusions: These data, although preliminary, show a reduction of cholesterol synthesis with aging. The finding might be related with a reduced metabolic need for cholesterol in advancing age, leading to a down-regulation of the main mechanisms of cholesterol uptake in the liver. The possible implications in terms of pharmacological management of hypercholesterolemia remain to be defined
