The turquoise killifish (Nothobranchius furzeri) as emerging ageing model: Systematic review and comparison with zebrafish, medaka and fugu

Selecting the most appropriate model organisms is crucial for studying ageing and ageing-related diseases. While vertebrate aging models offer valuable research feasibility due to their biological complexity and human relevance, their inherent lifespan limitations and high costs significantly restrict their experimental utility. The turquoise killifish (Nothobranchius furzeri, N. furzeri) is a relatively new animal model with the shortest lifespan among vertebrate models. We conducted a systematic review of the literature on N. furzeri following Prisma guidelines. We searched PubMed and Scopus databases, identifying 79 articles on ageing research in N. furzeri that met our inclusion criteria as of December 2024 and two independent reviewers screened and assessed all studies. We found that the ageing phenotypes of N. furzeri are highly consistent with those of other animal models. We screened and included literature on ageing mechanisms and focused our analysis on research results related to molecular biology and epigenetics. Compared to other fish models such as zebrafish, medaka, and fugu, N. furzeri offers several advantages for aging research, primarily due to its short lifespan, which provides unique insights from both physiological and genetic perspectives. However, several limitations must be considered. The current N. furzeri gene database remains incomplete, and the genetic background of this species is still not fully understood. Additionally, the mechanisms underlying the rapid ageing in N. furzeri have not yet been fully elucidated. Laboratory breeding of N. furzeri also lacks standardized processes and can be more challenging compared to other fish species. These factors may limit the widespread adoption of N. furzeri as an ageing model in the short term. Nevertheless, N. furzeri presents a novel, cost-effective, and rapid model for studying ageing-related diseases and mechanisms.