Pseudocapillarization and associated energy limitation in the aged rat liver

Authors

  • David G. Le Couteur,

    1. The Canberra Clinical School of the University of Sydney, Garran, Australia
    2. Department of Physiology of the University of Sydney, New South Wales, Australia
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  • Victoria C. Cogger,

    1. Department of Physiology of the University of Sydney, New South Wales, Australia
    2. Electron Microscope Unit of the University of Sydney, New South Wales, Australia
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  • Astrid M.A. Markus,

    1. The Canberra Clinical School of the University of Sydney, Garran, Australia
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  • Peta J. Harvey,

    1. The Canberra Clinical School of the University of Sydney, Garran, Australia
    2. The John Curtin School of Medical Research, Acton, Australia
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  • Zhan-Li Yin,

    1. The Canberra Clinical School of the University of Sydney, Garran, Australia
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  • Annick D. Ansselin,

    1. Department of Physiology of the University of Sydney, New South Wales, Australia
    2. Electron Microscope Unit of the University of Sydney, New South Wales, Australia
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  • Professor Allan J. McLean

    Corresponding author
    1. The Canberra Clinical School of the University of Sydney, Garran, Australia
    2. Department of Physiology of the University of Sydney, New South Wales, Australia
    • Department of Geriatric Medicine, The Canberra Hospital, Garran ACT 2605 Australia. fax: 61-2-6244-4036.
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Abstract

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 vitro31P 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.

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