Preprint: Reduced insulin/IGF-1 signalling in adult parents increases offspring fitness

Reduced expression of the insulin/insulin-like nutrient-sensing signalling (IIS) pathway gene daf-2 in adult Caenorhabditis elegans nematode worms increases longevity without affecting fecundity, but the effect of parental lifespan extension on adult offspring is largely unknown. We found that reduced IIS signalling in parental generation increases offspring fitness. We used RNA interference (RNAi) to silence daf-2 expression in sexually mature C. elegans hermaphrodites from three different genotypes: N2 wildtype, as well as ppw-1 and rrf-1 mutants that are deficient for RNAi in germline and soma, respectively. Long-lived daf-2 RNAi parents showed normal fecundity as self-fertilizing hermaphrodites and improved late-life reproduction when mated to males. Remarkably, the offspring of daf-2 RNAi parents produced more progeny and had higher Darwinian fitness across all three genotypes. Thus, reduced IIS signalling in adulthood improves offspring quality supporting the emerging view that suboptimally high levels of nutrient-sensing signalling in late-life lie at the heart of ageing.