Pseudocapillarization and associated energy limitation in the aged rat liver

Age-related impairment of drug metabolism by the liver is consistent with h epatocyte hypoxia, suggestive of the development of a diffusional barrier t o oxygen supply. Because the effects of aging; on the diffusional pathway ( sinusoidal endothelium and space of Disse) have not been described, we perf ormed comparative studies on the livers of Fischer F344 rats aged 4 to 7, 1 2 to 15, and 24 to 27 months. Light-microscopic examination revealed no evi dence of fibrosis, cirrhosis, or other specific pathology. In contrast, sca nning and transmission electron-microscopic examination revealed that aging is associated with pseudocapillarization of the sinusoidal endothelium, in dicated by defenestration with reduced porosity, thickening of the endothel ium, infrequent development of basal lamina, and only minor collagen deposi ts in the space of Disse, Furthermore, immunohistochemistry studies showed strong expression of collagen IV, moderate expression of factor VIII-relate d antigen, and weak expression of collagen I along the sinusoids of livers from old rats (P < .0001), In vitro P-31 magnetic resonance spectroscopy an alysis showed that aging is associated with changes in high-energy phosphat e and other metabolites, consistent with hepatocyte hypoxia. Aging in the l iver is associated with changes in the sinusoidal endothelium and space of Disse that may restrict the availability of oxygen and other substrates.