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

ABSTRACT: 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)-?, a known cell cycle inhibitor, were elevated in the aging liver. Here, we determine the role played by IFN-? 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-? producers-the macrophages and the natural killer cells, leads to a reduction in the IFN-? levels accompanied with the restoration of the DNA synthesis kinetics in the aged livers. Eighteen-month-old IFN-?-/- 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.

SUBMITTER: Singh P 

PROVIDER: S-EPMC3156631 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature