title: 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)-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.
authors: Department of Dermatology, Columbia University Medical Center, 1150 St. Nicholas Avenue, New York, NY 10032, USA. pallavi.singh02@gmail.com
authors: Pallavi
authors: P
authors: Singh
authors: Triona
authors: T
authors: Goode
authors: Adam
authors: A
authors: Dean
authors: Samir S
authors: SS
authors: Awad
authors: Gretchen J
authors: GJ
authors: Darlington
mesh_terms: D000375:Aging / Q000276:immunology* / Q000502:physiology; D000818:Animals; D002453:Cell Cycle; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000235:genetics / Q000502:physiology*; D007694:Killer Cells, Natural / Q000502:physiology; D008099:Liver / Q000502:physiology*; D008115:Liver Regeneration; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction / Q000502:physiology*; D051193:Toll-Like Receptors / Q000502:physiology
chemical_list: D012333:RNA, Messenger; D051193:Toll-Like Receptors; D007371:Interferon-gamma