title: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Bertolotti
authors.affiliation: Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Mussi
authors.affiliation: Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Pellegrini
authors.affiliation: Department of Health Sciences, University of Milano Bicocca, Monza, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Magni
authors.affiliation: Department of Health Sciences, University of Milano Bicocca, Monza, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Del Puppo
authors.affiliation: Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Ognibene
authors.affiliation: Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Carulli
authors.affiliation: Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Anzivino
authors.affiliation: Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Enrica
authors.initials: E
authors.lastname: Baldelli
authors.affiliation: Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Loria
authors.affiliation: Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Carulli
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000375:Aging / Q000378:metabolism* / Q000502:physiology; D002783:Cholestenones / Q000097:blood; D002784:Cholesterol / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism* / Q000502:physiology; D003430:Cross-Sectional Studies; D005260:Female; D042882:Gallstones / Q000097:blood / Q000378:metabolism / Q000503:physiopathology; D008401:Gas Chromatography-Mass Spectrometry; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010840:Phytosterols / Q000097:blood; D012855:Sitosterols / Q000097:blood
chemical_list: D002783:Cholestenones; D010840:Phytosterols; D012855:Sitosterols; C002656:7 alpha-hydroxy-4-cholesten-3-one; C021273:campesterol; C025473:gamma-sitosterol; C001521:lathosterol; D002784:Cholesterol
keywords: aging; cardiovascular risk; cholesterol metabolism; cholesterol synthesis; gallstone disease