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Pseudocapillarization and associated energy limitation in the aged rat liver
Author(s) -
Le Couteur David G.,
Cogger Victoria C.,
Markus Astrid M.A.,
Harvey Peta J.,
Yin ZhanLi,
Ansselin Annick D.,
McLean Allan J.
Publication year - 2001
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1053/jhep.2001.22754
Subject(s) - perisinusoidal space , cirrhosis , endothelium , hepatocyte , sinusoid , pathology , fibrosis , hypoxia (environmental) , interstitial space , biology , chemistry , medicine , endocrinology , in vitro , oxygen , biochemistry , organic chemistry
Age‐related impairment of drug metabolism by the liver is consistent with hepatocyte hypoxia, suggestive of the development of a diffusional barrier to oxygen supply. Because the effects of aging on the diffusional pathway (sinusoidal endothelium and space of Disse) have not been described, we performed comparative studies on the livers of Fischer F344 rats aged 4 to 7, 12 to 15, and 24 to 27 months. Light‐microscopic examination revealed no evidence of fibrosis, cirrhosis, or other specific pathology. In contrast, scanning and transmission electron‐microscopic examination revealed that aging is associated with pseudocapillarization of the sinusoidal endothelium, indicated by defenestration with reduced porosity, thickening of the endothelium, infrequent development of basal lamina, and only minor collagen deposits in the space of Disse. Furthermore, immunohistochemistry studies showed strong expression of collagen IV, moderate expression of factor VIII‐related antigen, and weak expression of collagen I along the sinusoids of livers from old rats ( P < .0001). In vitro 31 P magnetic resonance spectroscopy analysis showed that aging is associated with changes in high‐energy phosphate and other metabolites, consistent with hepatocyte hypoxia. Aging in the liver is associated with changes in the sinusoidal endothelium and space of Disse that may restrict the availability of oxygen and other substrates.