Biology of Ageing
Calorie restriction delays age-related defenestration of the liver sinusoidal endothelium
HA Jamieson, VC Cogger, SN Hilmer, R Cheluvappa, A Everitt, R Fraser, D Abernethy, R de Cabo, DG Le Couteur
Previous work by our group has demonstrated that aging causes changes in the liver sinusoidal endothelium including a loss of sinusoidal fenestrae and an increase in thickness of the endothelium. This delays the clearance of chylomicron-remnants and may partly explain why ageing is a risk factor for the cardiovascular diseases such as strokes and heart attacks.
Limiting the caloric intake of animals by approximately 30% has been consistently shown to extend lifespan and reduce the incidence of age-related diseases. In this collaborative project with the United States National Institute on Aging, we showed that calorie restriction prevented the development of age-related defenestration. This is the first time that a treatment has been shown to prevent defenestration in old animals. This provides a potential mechanism for how calorie restriction extends lifespan in mammals. Future work will assess if calorie restriction affects the clearance of lipid rich blood particles.
Link here to the Journal of Gastroenterology and Hepatology to access the full text for this study.
Caloric restriction reduces age-related pseudocapillarization of the hepatic sinusoid
Hamish A Jamieson, Sarah N Hilmer, Victoria C Cogger, Alessandra Warren, Rajkumar Cheluvappa, Darrell R Abernethy, Arthur V Everitt, Robin Fraser, Rafael de Cabo, and David G Le Couteur
Age-related changes in the hepatic sinusoid, called pseudocapillarization, may contribute to the pathogenesis of dyslipidaemia. 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.
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