Elevated interferon gamma signaling contributes to impaired regeneration in the aged liver

J Gerontol A Biol Sci Med Sci. 2011 Sep;66(9):944-56. doi: 10.1093/gerona/glr094. Epub 2011 Jun 30.


Our previous study on immune-related changes in the aged liver described immune cell infiltration and elevation of inflammation with age. Levels of interferon (IFN)-γ, a known cell cycle inhibitor, were elevated in the aging liver. Here, we determine the role played by IFN-γ in the delayed regenerative response observed in the aged livers. We observed elevated IFN signaling in both aged hepatocytes and regenerating livers post-partial hepatectomy. In vivo deletion of the major IFN-γ producers-the macrophages and the natural killer cells, leads to a reduction in the IFN-γ levels accompanied with the restoration of the DNA synthesis kinetics in the aged livers. Eighteen-month-old IFN-γ-/- mice livers, upon resection, exhibited an earlier entry into the cell cycle compared with age-matched controls. Thus, our study strongly suggests that an age-related elevation in inflammatory conditions in the liver often dubbed as "inflammaging" has a detrimental effect on the regenerative response.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / immunology*
  • Aging / physiology
  • Animals
  • Cell Cycle
  • Immunity, Innate
  • Interferon-gamma / genetics
  • Interferon-gamma / physiology*
  • Killer Cells, Natural / physiology
  • Liver / physiology*
  • Liver Regeneration*
  • Macrophages / physiology
  • Mice
  • Mice, Inbred C57BL
  • RNA, Messenger / analysis
  • Signal Transduction / physiology*
  • Toll-Like Receptors / physiology


  • RNA, Messenger
  • Toll-Like Receptors
  • Interferon-gamma