title: Caloric restriction reduces age-related pseudocapillarization of the hepatic sinusoid.
abstract: Age-related changes in the hepatic sinusoid, called pseudocapillarization, may contribute to the pathogenesis of dyslipidemia. Caloric restriction (CR) is a powerful model for the study of aging because it extends lifespan. We assessed the effects of CR on the hepatic sinusoid to determine whether pseudocapillarization is preventable and hence a target for the prevention of age-related dyslipidemia. Livers from young (6 months) and old (24 months) CR and ad libitum fed (AL) F344 rats were examined using electron microscopy and immunohistochemistry. In old age, there was increased thickness of the liver sinusoidal endothelium and reduced endothelial fenestration porosity. In old CR rats, endothelial thickness was less and fenestration porosity was greater than in old AL rats. Immunohistochemistry showed that CR prevented age-related decrease in caveolin-1 expression and increase in peri-sinusoidal collagen IV staining, but did not alter the age-related increase of von Willebrand's factor. CR reduces age-related pseudocapillarization of the hepatic sinusoid and correlates with changes in caveolin-1 expression.
authors.affiliation: Centre for Education and Research on Ageing and ANZAC Medical Research Institute, Concord Hospital, Concord, NSW, Australia.
authors.forename: Hamish A
authors.initials: HA
authors.lastname: Jamieson
authors.forename: Sarah N
authors.initials: SN
authors.lastname: Hilmer
authors.forename: Victoria C
authors.initials: VC
authors.lastname: Cogger
authors.forename: Alessandra
authors.initials: A
authors.lastname: Warren
authors.forename: Rajkumar
authors.initials: R
authors.lastname: Cheluvappa
authors.forename: Darrell R
authors.initials: DR
authors.lastname: Abernethy
authors.forename: Arthur V
authors.initials: AV
authors.lastname: Everitt
authors.forename: Robin
authors.initials: R
authors.lastname: Fraser
authors.forename: Rafael
authors.initials: R
authors.lastname: de Cabo
authors.forename: David G
authors.initials: DG
authors.lastname: Le Couteur
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D031204:Caloric Restriction / Q000379:methods*; D002196:Capillaries / Q000648:ultrastructure; D051242:Caveolin 1 / Q000032:analysis; D024141:Collagen Type IV / Q000032:analysis; D042783:Endothelial Cells / Q000502:physiology / Q000648:ultrastructure; D004730:Endothelium, Vascular / Q000502:physiology / Q000648:ultrastructure; D007150:Immunohistochemistry / Q000379:methods; D008099:Liver / Q000098:blood supply / Q000502:physiology* / Q000648:ultrastructure; D008855:Microscopy, Electron, Scanning / Q000379:methods; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D051242:Caveolin 1; D024141:Collagen Type IV