The Germline Impacts Life Span

One evolutionary perspective on life is that the individuals making up a species are secondary concerns, mere wrappers for the all-important germline cells. Evolution optimizes for success in propagation of the germline lineage, not the success of the individual. With that in mind, one might expect to find that the germline can influence the body. That influence doesn't have to be a net positive for the individual, as noted here. The individual is disposable, and health only matters insofar as it enhances reproductive fitness in the eternal, ever-shifting arms race that takes place over evolutionary time.

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 differentiation at discrete stages, and examine how different 'flavors' of infertility impact life-history.

We first constructed a comprehensive single-cell gonadal atlas, providing cell-type-specific markers for downstream phenotypic analysis. Next, investigating our genetic models revealed that only germline depletion enhanced female damage repair, while arresting germline differentiation did not. Conversely, germline-depleted males were significantly long-lived, indicating that the mere presence of the germline can negatively affect lifespan. Transcriptomic analysis highlighted enrichment of pro-longevity pathways and genes, with functional conservation in germline-depleted C. elegans. Finally, germline depletion extended male healthspan through rejuvenated metabolic functions.

Our results suggest that different germline manipulation paradigms can yield pronounced sexually dimorphic phenotypes, implying alternative mechanisms to classical evolutionary tradeoffs.

Link: https://doi.org/10.1101/2023.12.18.572041

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