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Peer-reviewedCC BYEMBO Reports

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

  • Eugen Ballhysa1
  • Roberto Ripa1
  • Nadine Hochhard1
  • Tin Tin Manh Nguyen1
  • Jennifer Brazzell2
  • Youngjun Park1
  • Baptiste Ferreri3
  • Elena Hoffmann4
  • Raymond Laboy5
  • Joachim David Steiner1
  • Adam Antebi1
5 affiliations
  1. 1Max Planck Institute for Biology of Ageing
  2. 2IDEXX BioAnalytics
  3. 3Sorbonne Université
  4. 4University of Cologne
  5. 5Joslin Diabetes Center, Harvard Medical School
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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 β-galactosidase activity and higher levels of cell proliferation, without detectable differences in immune infiltration. Despite these attenuated aging signatures, lifespan is not extended. Together, these findings reveal that while cGAS loss alleviates senescence and age-related signatures, additional mechanisms constrain longevity.

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Cite

BibTeXRIS
BibTeX
@article{ballhysa2026loss,
  title = {{Loss of killifish cGAS attenuates age-related signatures but does not affect organismal life span}},
  author = {Eugen Ballhysa and Roberto Ripa and Nadine Hochhard and Tin Tin Manh Nguyen and Jennifer Brazzell and Youngjun Park and Baptiste Ferreri and Elena Hoffmann and Raymond Laboy and Joachim David Steiner and Adam Antebi},
  journal = {EMBO Reports},
  year = {2026},
  month = sep,
  doi = {10.1038/s44319-026-00917-y},
  url = {https://doi.org/10.1038/s44319-026-00917-y},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Loss of killifish cGAS attenuates age-related signatures but does not affect organismal life span
AU  - Eugen Ballhysa
AU  - Roberto Ripa
AU  - Nadine Hochhard
AU  - Tin Tin Manh Nguyen
AU  - Jennifer Brazzell
AU  - Youngjun Park
AU  - Baptiste Ferreri
AU  - Elena Hoffmann
AU  - Raymond Laboy
AU  - Joachim David Steiner
AU  - Adam Antebi
PY  - 2026
DA  - 2026/09/01
JO  - EMBO Reports
DO  - 10.1038/s44319-026-00917-y
UR  - https://doi.org/10.1038/s44319-026-00917-y
AB  - 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 β-galactosidase activity and higher levels of cell proliferation, without detectable differences in immune infiltration. Despite these attenuated aging signatures, lifespan is not extended. Together, these findings reveal that while cGAS loss alleviates senescence and age-related signatures, additional mechanisms constrain longevity.
SN  - 1469-3178
ER  -