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.

Age-associated alterations in cholesterol homeostasis: evidence from a cross-sectional study in a Northern Italy population / Bertolotti, Marco; Mussi, Chiara; Pellegrini, E; Magni, A; Del Puppo, M; Ognibene, Silvia; Carulli, Lucia; Anzivino, C; Baldelli, Enrica; Loria, Paola; Carulli, N.. - In: CLINICAL INTERVENTIONS IN AGING. - ISSN 1178-1998. - STAMPA. - 9:(2014), pp. 425-432. [10.2147/CIA.S57714]

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

BERTOLOTTI, Marco;MUSSI, Chiara;OGNIBENE, Silvia;CARULLI, Lucia;BALDELLI, Enrica;LORIA, Paola;
2014

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.
2014
9
425
432
Age-associated alterations in cholesterol homeostasis: evidence from a cross-sectional study in a Northern Italy population / Bertolotti, Marco; Mussi, Chiara; Pellegrini, E; Magni, A; Del Puppo, M; Ognibene, Silvia; Carulli, Lucia; Anzivino, C; Baldelli, Enrica; Loria, Paola; Carulli, N.. - In: CLINICAL INTERVENTIONS IN AGING. - ISSN 1178-1998. - STAMPA. - 9:(2014), pp. 425-432. [10.2147/CIA.S57714]
Bertolotti, Marco; Mussi, Chiara; Pellegrini, E; Magni, A; Del Puppo, M; Ognibene, Silvia; Carulli, Lucia; Anzivino, C; Baldelli, Enrica; Loria, Paola...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1010727
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