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Journal of Lipid Research, Vol. 43, 1950-1959, November 2002
Copyright © 2002 by Lipid Research, Inc.

Aging per se is an independent risk factor for cholesterol gallstone formation in gallstone susceptible mice

David Q-H. Wang¹

Department of Medicine, Gastroenterology Division, Beth Israel Deaconess Medical Center, Harvard Medical School and Harvard Digestive Diseases Center, Boston, MA

¹ To whom correspondence should be addressed. e-mail: dqwang{at}caregroup.harvard.edu

Cholesterol gallstones occur rarely in childhood and adolescence and increase linearly with age in both genders. To explore whether aging per se increases cholesterol saturation of bile and gallstone prevalence, and to investigate age-related changes in hepatic and biliary lipid metabolism, we studied gallstone-susceptible C57L mice and resistant AKR mice of both genders fed 8 weeks with a lithogenic diet containing 1% cholesterol, 0.5% cholic acid, and 15% butter fat starting at (young adult) 8, (older adult) 36, and (aged) 50-weeks-of-age. After the 8-week feeding, gallstone prevalence, gallbladder size, biliary lipid secretion rate, and HMG-CoA reductase activity were significantly greater but cholesterol 7-hydroxylase activity was lower in C57L mice of both genders compared with AKR mice. Increasing age augmented biliary secretion and intestinal absorption of cholesterol, reduced hepatic synthesis and biliary secretion of bile salts, and decreased gallbladder contractility, all of which increased susceptibility to cholesterol cholelithiasis in C57L mice.

We conclude that aging per se is an independent risk factor for cholesterol gallstone formation. Because aging increases significantly biliary cholesterol hypersecretion and gallstone prevalence in C57L mice carrying Lith genes, it is highly like that Longevity (aging) genes can enhance lithogenesis of Lith (gallstone) genes.

Abbreviations: CCK-8, sulfated cholecystokinin octapeptide; CSI, cholesterol saturation index; HMG-CoA, hydroxy-3-methylglutaryl coenzyme A

Supplementary key words bile salt • bile flow • phospholipid • gallbladder size • mucin gel • HMG-CoA reductase • cholesterol 7-hydroxylase

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