The African turquoise killifish: a compressed vertebrate window on the molecular hallmarks of ageing and age-related disease.

Abstract

Research into vertebrate ageing needs model organisms in which the whole lifespan is experimentally tractable while the underlying biology stays recognisably vertebrate. The African turquoise killifish (Nothobranchius furzeri) meets both requirements more fully than any other currently available laboratory vertebrate. Adapted to the ephemeral pools of south-eastern Africa, completing its life cycle in a few months, it is the shortest-lived vertebrate that can be bred conveniently in captivity, showing progressive, systemic decline rather than abrupt early death. Over the past decade, a sequenced genome, CRISPR/Cas9 engineering, standardised husbandry and multi-omic atlases have turned it into a systems-level ageing platform. Here, we review how killifish reproduce the molecular hallmarks of ageing, from genomic instability and telomere attrition to epigenetic changes, mitochondrial dysfunction and cellular senescence, while making clear that the depth of that evidence differs markedly between hallmarks. We also examine how immunosenescence and inflammageing could form the axis integrating these cell-intrinsic hallmarks with organ-level disease. We then survey how the killifish is used to model age-related disease of the brain, heart, eye and musculoskeletal system, and to screen genetic, pharmacological and dietary interventions within a single generation. We also address where the current literature conflicts, namely on telomere attrition, the nature of diapause and the direction of epigenetic change. While the killifish does not replace longer-lived models, its contribution to modern research is to compress vertebrate ageing into a timeframe in which mechanism and intervention can be studied together.