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

Loss of cGAS in killifish reduces age-related cellular senescence and transcriptional aging signatures but does not extend lifespan.

• Why it matters: Understanding how innate immune pathways influence aging can reveal targets to mitigate age-related decline; however, their direct impact on lifespan remains unclear.
• What they did: Researchers generated cGAS knockout killifish and examined cellular and organismal aging markers, including DNA damage, senescence indicators, and transcriptional changes across lifespan stages.
• The result: While cGAS deficiency decreased senescence markers and dampened aging signatures, it did not result in longer lifespan, indicating other mechanisms limit longevity despite reduced aging phenotypes.