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Abstract

Our earlier study on immune related changes in the aged liver described immune cell
infiltration and elevation of inflammation with age. The levels of inflammatory cytokine
-IFN-, known to cause inhibition of cell cycle progression, were elevated in the aging
liver. Studies have shown that IFN- has a detrimental effect on the regenerative
capacity of the liver.

In our current study, we determine the effect of prevailing

inflammatory conditions, including higher IFN- levels, on the delayed regeneration


observed in the aged livers after resection. Interferon signaling is elevated in the aged
hepatocytes and an even greater increase in the levels of interferon related genes is
observed after partial hepatectomy. We demonstrate that the deletion of the major IFN producing immune cells the macrophages and the natural killer cells, from the aged
liver prior to partial hepatectomy leads to restoration of the magnitude of BrdU
incorporation during DNA synthesis in old animals.

Removal of these cells is

accompanied with a reduction in the IFN- levels. Eighteen month old IFN- -/- mice
were subjected to partial hepatectomy to determine the effects of deletion of IFN- from
the old livers. Despite increased frailty and high mortality after PH, aged IFN- -/- mice
exhibited an earlier entry into the cell cycle compared to age matched wild type mice.
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 of the liver.