The cGAS-STING pathway is an modifier of genomic instability syndromes.

Mutations in genes involved in DNA damage repair (DDR) often lead to premature aging syndromes. While recent evidence suggests that inflammation, alongside mutation accumulation and cell death, may drive disease phenotypes, its precise contribution to pathophysiology remains unclear. Here, by modeling Ataxia Telangiectasia (A-T) and Bloom Syndrome in the African turquoise killifish ( ), we replicate key phenotypes of DDR syndromes, including infertility, cytoplasmic DNA fragments, and reduced lifespan.