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Reduced insulin signalling in adulthood protects soma and germline under mutation accumulation

By Elizabeth ML Duxbury, Hanne Carlsson, Kris Sales, Simone Immler, Tracey Chapman, Alexei A. Maklakov

Posted 19 Aug 2020
bioRxiv DOI: 10.1101/2020.08.19.257253

Dominant theory maintains that organisms age due to resource allocation trade-offs between the immortal germline and the disposable soma. Strikingly, adulthood-only downregulation of insulin signalling, an evolutionarily conserved pathway regulating resource allocation between reproduction and soma, increases lifespan and offspring fitness without fecundity cost in the nematode, Caenorhabditis elegans. Nevertheless, theory suggests that reduced germline maintenance can be a hidden cost of lifespan extension. We ran a mutation accumulation (MA) experiment and downregulated insulin signalling in half of the 400 MA lines by silencing daf-2 gene expression using RNA interference (RNAi) across 40 generations. Adulthood-only daf-2 RNAi reduced extinction of MA lines both under UV-induced and spontaneous mutation accumulation. Fitness of the surviving UV-induced MA lines was higher under daf-2 RNAi. Our results suggest that reduced insulin signalling protects the soma and the germline and imply that suboptimal gene expression in adulthood is a major driver of organismal ageing. ### Competing Interest Statement The authors have declared no competing interest.

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