The germline regulates longevity and somatic repair in a sex-specific manner

Moses, E.; Atlan, T.; Sun, X.; Franek, R.; Siddiqui, A.; Marinov, G. K.; Shifman, S.; Zucker, D. M.; Oron-Gottesman, A.; Greenleaf, W. J.; Cohen, E.; Ram, O.; Harel, I.

doi:10.1101/2023.12.18.572041

bioRxiv · 10.1101/2023.12.18.572041

The germline regulates longevity and somatic repair in a sex-specific manner

Moses, E.·Atlan, T.·Sun, X.·Franek, R.·Siddiqui, A.·Marinov, G. K.·Shifman, S.·Zucker, D. M.·Oron-Gottesman, A.·Greenleaf, W. J.·Cohen, E.·Ram, O.·Harel, I.

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Abstract

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.

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Moses, E., Atlan, T., Sun, X., Franek, R., Siddiqui, A., Marinov, G. K., Shifman, S., Zucker, D. M., Oron-Gottesman, A., Greenleaf, W. J., Cohen, E., Ram, O., Harel, I.. 2023-12-18. The germline regulates longevity and somatic repair in a sex-specific manner. https://doi.org/10.1101/2023.12.18.572041

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