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Alloveda Liver Update: Liver Regeneration and Aging

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Dr KK Aggarwal    07 October 2020

An article published in Current Gerontology and Geriatrics Research discussed that several organ systems undergo significant age-related deficits; however, based on studies in old animal models and elderly humans, the liver appears to be relatively protected from such changes. The liver has a notable feature - the capacity to regenerate its mass following partial hepatectomy.

Evidence suggests that aging tends to jeopardize the livers regenerative capacity, both in the rate and the extent to which the organs original volume is restored. However, there has been modest definitive information regarding which cellular and molecular mechanisms regulating hepatic regeneration are impacted by aging.

Changes in hepatic sensitivity to growth factors, such as epidermal growth factor (EGF), appear to affect regeneration in old animals. On the other hand, recent studies suggest that reduced phosphorylation and dimerization of the EGF receptor, key steps in the activation of the extracellular signal-regulated kinase pathway, and subsequent cell proliferation are accountable. Some other studies have shown that aging affects the upregulation of a Forkhead Box transcription factor (FoxM1B), vital for growth hormone-stimulated liver regeneration.

Hence, aging appears to compromise liver regeneration via several pathways, resulting in a reduction in the rate of regeneration, but not in the capacity to restore the organ to its original volume.

Furthermore, the relative efficacies of normal, cell-cycle-induced hepatocyte proliferation compared to an independent pathway involving hepatocyte hypertrophy in maintaining liver functions requires further investigation. The roles of VEGF, serotonin and liver sinusoidal pseudocapillarization also need to be investigated.

Most evidence shows that the age of the liver donor or recipient exerts only a modest impact on post-transplantation patient’s survival. The findings suggest that a pre-transplantation regimen of growth factors in potential elderly liver recipients deserves further consideration.

Source: Schmucker DL, Sanchez H. Liver Regeneration and Aging: A Current Perspective. Current Gerontology and Geriatrics Research. Volume 2011. Article ID 526379. https://doi.org/10.1155/2011/526379

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