期刊
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
卷 66, 期 9, 页码 944-956出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/gerona/glr094
关键词
Aging; Inflammation; Gamma interferon; Liver regeneration; Partial hepatectomy
资金
- National Institutes of Health [PO1 AG20752, AG028865]
- Texas Medical Center Digestive Disease Center [DK56338, DK53045]
- Ellison Medical Foundation
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)-gamma, a known cell cycle inhibitor, were elevated in the aging liver. Here, we determine the role played by IFN-gamma 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-gamma producers-the macrophages and the natural killer cells, leads to a reduction in the IFN-gamma levels accompanied with the restoration of the DNA synthesis kinetics in the aged livers. Eighteen-month-old IFN-gamma-/- 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.
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