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 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.

AFM imaging of fenestrated liver sinusoidal endothelial cells

“…In this study the authors could demonstrate that the elasticity value increased two-to four-fold when compared to younger cells. A similar approach could shed light on the ageing LSEC under different experimental conditions (Jamieson et al, 2007).…”

Transgenic flax overexpressing polyphenols as a potential anti-inflammatory dietary agent

“…Male C57BL/6J mice receiving a Western diet (high levels of fat and carbohydrates) demonstrated steatohepatitis and fibrosis, sinusoidal endothelium thickening, early capillarization, endothelial cell defenestration and the formation of subendothelial basal lamina (DeLeve, Wang, Kanel, Atkinson, & McCuskey, 2008). Thickened endothelium and defenestration may weaken the transfer of substrates between the sinusoid and hepatocytes, particularly that of lipoproteins (Jamieson et al, 2007). The liver sinusoidal endothelium is susceptible to oxidative stress.…”

The liver sinusoidal endothelial cell: a cell type of controversial and confusing identity

“…Variation in the expression of most of these molecules by LSECs has been observed during the development of certain liver diseases including chronic inflammatory disorders, fibrosis, viral infection, or tumor development (19, 23-25, 79, 80, 83, 87, 88). Normal aging is associated with sinusoidal capillarization (5,9,31,47), leading to changes in the expression of marker molecules along the sinusoidal endothelium. This fact is not often taken into consideration in studies of human liver that frequently involve samples from individuals of different age.…”