Loss of killifish cGAS attenuates age-related signatures but does not affect organismal life span

ABSTRACT: The cGAS/STING pathway is a central innate immune signaling pathway responsive to cytosolic DNA. Chronic activation of this pathway promotes numerous age-related pathologies, but its impact on lifespan remains unknown. Here we engineer a cGAS knockout (KO) in the turquoise killifish Nothobranchius furzeri to assess effects on physiology and aging. In cultured fibroblasts, cGAS deficiency results in elevated DNA damage, but reduces radiation-induced senescence, and enhances cellular proliferation. In vivo, cGAS KO attenuates DNA damage-induced transcriptional responses in young fish, and blunts age-associated transcriptional changes in old fish, consistent with dampening of senescence and aging. Accordingly, old cGAS KO animals exhibit lower levels of senescence-associated -galactosidase a

SUBMITTER: Eugen Ballhysa 

PROVIDER: S-SCDT-10_1038-S44319-026-00917-Y | biostudies-other |

REPOSITORIES: biostudies-other