Classical evolutionary theories propose tradeoffs among reproduction, damage repair and lifespan. However, the specific role of the germline in shaping vertebrate aging remains largely unknown. In this study, we used the turquoise killifish (Nothobranchius furzeri) to genetically arrest germline development at discrete stages and examine how different modes of infertility impact life history. We first constructed a comprehensive single-cell gonadal atlas, providing cell-type-specific markers for downstream phenotypic analysis. We show here that germline depletion-but not arresting germline differentiation-enhances damage repair in female killifish. Conversely, germline-depleted males instead showed an extension in lifespan and rejuvenated metabolic functions. Through further transcriptomic analysis, we highlight enrichment of pro-longevity pathways and genes in germline-depleted male killifish and demonstrate functional conservation of how these factors may regulate longevity in germline-depleted Caenorhabditis elegans. Our results, therefore, demonstrate that different germline manipulation paradigms can yield pronounced sexually dimorphic phenotypes, implying alternative responses to classical evolutionary tradeoffs.

Center for Personal Dynamic Regulomes Stanford University Stanford CA USA

Chan Zuckerberg Biohub San Francisco CA USA

Department of Applied Physics Stanford University Stanford CA USA

Department of Biochemistry and Molecular Biology Institute for Medical Research Israel Canada Hebrew University School of Medicine Jerusalem Israel

Department of Biochemistry Silberman Institute Hebrew University of Jerusalem Givat Ram Jerusalem Israel

Department of Genetics Silberman Institute Hebrew University of Jerusalem Givat Ram Jerusalem Israel

Department of Genetics Stanford University Stanford CA USA

Department of Statistics and Data Science Hebrew University of Jerusalem Jerusalem Israel

South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses University of South Bohemia in Ceske Budejovice Vodnany Czech Republic

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bioRxiv. 2024 May 12:2023.12.18.572041. doi: 10.1101/2023.12.18.572041. PubMed

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