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.

Tissue-specific landscape of protein aggregation and quality control in an aging vertebrate.

Protein aggregation is a hallmark of age-related neurodegeneration. Yet, aggregation during normal aging and in tissues other than the brain is poorly understood. Here, we leverage the African turquoise killifish to systematically profile protein aggregates in seven tissues of an aging vertebrate.

Identification of protein aggregates in the aging vertebrate brain with prion-like and phase-separation properties.

Protein aggregation, which can sometimes spread in a prion-like manner, is a hallmark of neurodegenerative diseases. However, whether prion-like aggregates form during normal brain aging remains unknown. Here, we use quantitative proteomics in the African turquoise killifish to identify protein aggregates that accumulate in old vertebrate brains.

Genetic perturbation of AMP biosynthesis extends lifespan and restores metabolic health in a naturally short-lived vertebrate.

During aging, the loss of metabolic homeostasis drives a myriad of pathologies. A central regulator of cellular energy, the AMP-activated protein kinase (AMPK), orchestrates organismal metabolism. However, direct genetic manipulations of the AMPK complex in mice have, so far, produced detrimental phenotypes.