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Center for Personal Dynamic Regulomes... 1 Chan Zuckerberg Biohub San Francisco ... 1 Department of Applied Physics Stanfor... 1 Department of Biochemistry Silberman ... 1 Department of Biochemistry and Molecu... 1 Department of Genetics Silberman Inst... 1 Department of Genetics Stanford Unive... 1 Department of Statistics and Data Sci... 1 South Bohemian Research Center of Aqu... 1
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Center for Personal Dynamic Regulomes... 1 Chan Zuckerberg Biohub San Francisco ... 1 Department of Applied Physics Stanfor... 1 Department of Biochemistry Silberman ... 1 Department of Biochemistry and Molecu... 1 Department of Genetics Silberman Inst... 1 Department of Genetics Stanford Unive... 1 Department of Statistics and Data Sci... 1 South Bohemian Research Center of Aqu... 1
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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.
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