Many organ systems exhibit significant age-related deficits, but, based on studies in old rodents and elderly humans, the liver appears to be relatively protected from such changes. A remarkable feature of the liver is its capacity to regenerate its mass following partial hepatectomy. Reports suggests that aging compromises the liver's regenerative capacity, both in the rate and to the extent the organ's original volume is restored. There has been modest definitive information as to which cellular and molecular mechanisms regulating hepatic regeneration are affected by aging. Changes in hepatic sensitivity to growth factors, for example, epidermal growth factor (EGF), appear to influence regeneration in old animals. Studies have demonstrated (a) a 60% decline in EGF binding to hepatocyte plasma membranes, (b) reduced expression of the hepatic high affinity EGF receptor and (c) a block between G1 and S-phases of the cell cycle in old rats following EGF stimulation. Recent studies suggest that reduced phosphorylation and dimerization of the EGF receptor, criticalsteps in the activation of the extracellular signal-regulatedkinase pathway and subsequent cell proliferation are responsible. Other studies have demonstrated that aging affects theupregulation of a Forkhead Box transcription factor, FoxM1B, whichis essential for growth hormone-stimulated liver regeneration inhepatectomized mice. Aging appears to compromise liverregeneration by influencing several pathways, the result of whichis a reduction in the rate of regeneration, but not in thecapacity to restore the organ to its original volume.
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