The killifish germline regulates longevity and somatic repair in a sex-specific manner
The killifish germline regulates longevity and somatic repair in a sex-specific manner
Classical evolutionary theories propose tradeoffs between reproduction, damage repair, and lifespan. However, the specific role of the germline in shaping vertebrate aging remains largely unknown. Here, we use the turquoise killifish (N. furzeri) to genetically arrest germline development at discrete stages, and examine how different modes of infertility impact life-history. We first construct a comprehensive single-cell gonadal atlas, providing cell-type-specific markers for downstream phenotypic analysis. Next, we show 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 C. elegans. Our results therefore demonstrate that different germline manipulation paradigms can yield pronounced sexually dimorphic phenotypes, implying alternative responses to classical evolutionary tradeoffs.
Shifman Sagiv、Zucker David M.、Oron-Gottesman Adi、Ram Oren、Atlan Tehila、Siddiqui Atif、Harel Itamar、Sun Xue、Marinov Georgi K.、Greenleaf William J.、Franek Roman、Moses Eitan、Cohen Ehud
Department of Genetics, the Silberman Institute, the Hebrew University of JerusalemDepartment of Statistics and Data Science, Hebrew University of JerusalemDepartment of Genetics, the Silberman Institute, the Hebrew University of JerusalemDepartment of Biochemistry, the Silberman Institute, the Hebrew University of JerusalemDepartment of Genetics, the Silberman Institute, the Hebrew University of JerusalemDepartment of Biochemistry and Molecular Biology, the Institute for Medical Research Israel-Canada (IMRIC), the Hebrew University School of MedicineDepartment of Genetics, the Silberman Institute, the Hebrew University of JerusalemDepartment of Biochemistry, the Silberman Institute, the Hebrew University of JerusalemDepartment of Genetics, Stanford UniversityDepartment of Genetics, Stanford University||Center for Personal Dynamic Regulomes, Stanford University||Department of Applied Physics, Stanford University||Chan Zuckerberg BiohubDepartment of Genetics, the Silberman Institute, the Hebrew University of Jerusalem||University of South Bohemia in Ceske Budejovice, South Bohemian Research Center of Aquaculture and Biodiversity of HydrocenosesDepartment of Genetics, the Silberman Institute, the Hebrew University of JerusalemDepartment of Biochemistry and Molecular Biology, the Institute for Medical Research Israel-Canada (IMRIC), the Hebrew University School of Medicine
遗传学生理学分子生物学
Shifman Sagiv,Zucker David M.,Oron-Gottesman Adi,Ram Oren,Atlan Tehila,Siddiqui Atif,Harel Itamar,Sun Xue,Marinov Georgi K.,Greenleaf William J.,Franek Roman,Moses Eitan,Cohen Ehud.The killifish germline regulates longevity and somatic repair in a sex-specific manner[EB/OL].(2025-03-28)[2025-05-07].https://www.biorxiv.org/content/10.1101/2023.12.18.572041.点此复制
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