A Model to Unify Toxicology and Aging Research: Turquoise Killifish, the Cultivated Vertebrate with the Shortest Lifespan

Key Contribution:
Environmental pollution significantly contributes to the climate crisis and poses major threats to human and environmental health. Toxic substances are present in food and drinking water, leading individuals to be exposed for extended periods or throughout their entire lives. Some pollutants can accelerate aging; however, studies on the effects of contaminants on this process are limited due to methodological challenges. In this context, the turquoise killifish N. furzeri emerges as a powerful animal model, possessing the fastest life cycle ever documented for a vertebrate, thereby bridging the important fields of aging research and toxicology.

Abstract
Environmental pollution has emerged as one of the most significant threats to human and ecosystem health, with growing evidence suggesting that chronic exposure to toxic substances may accelerate aging. The concept of gerontogens, toxic compounds capable of accelerating this biological process, has gained increasing attention in toxicological research, particularly in the context of global demographic shifts toward older populations. Current research on gerontogens relies heavily on invertebrate models with short lifespans, such as Caenorhabditis elegans, Drosophila melanogaster, and Saccharomyces cerevisiae, which are valuable for studying conserved mechanisms in aging pathways, but present significant limitations for translational accuracy to many aspects of vertebrate biology. Vertebrate models traditionally employed in toxicology, including mice and zebrafish, require substantially longer experimental timelines and higher financial investments, making lifetime exposure and aging assays particularly challenging. In this context, the turquoise killifish Nothobranchius furzeri emerges as a highly promising vertebrate model for aging toxicology research. Recognized as the shortest-lived vertebrate species maintained under laboratory conditions, N. furzeri reaches sexual maturity within 14 days and displays complete senescence by 4 months of age, at which point individuals are considered elderly, offering a decisive advantage over conventional vertebrate models. Furthermore, its capacity for embryonic diapause enables practical embryo storage, long-distance transport, and synchronized hatching, greatly facilitating experimental designs. Although N. furzeri is well established in gerontological research, with studies addressing hallmarks of aging such as telomere shortening, neurodegeneration, and cellular senescence, its application in ecotoxicology remains remarkably limited, with fewer than 10 published studies to date. This article argues that N. furzeri may represent a critical bridge between toxicology and aging research, offering an efficient and translationally relevant platform for investigating the effects of environmental contaminants on vertebrate aging. Current limitations of the model, such as lack of husbandry standardization, are also discussed. Expanding its use in this field holds considerable potential for advancing evidence-based strategies in public health and environmental conservation related to chronic exposure to contaminants.