Experimentally reduced insulin/IGF-1 signalling in adulthood extends lifespan of parents and improves Darwinian fitness of their offspring

Abstract

Classical theory maintains that ageing evolves via energy trade-offs between reproduction and survival leading to accumulation of unrepaired cellular damage with age. In contrast, the emerging new theory postulates that ageing evolves because of deleterious late-life hyper-function of reproduction-promoting genes leading to excessive biosynthesis in late-life. The hyper-function theory uniquely predicts that optimizing nutrient-sensing molecular signalling in adulthood can simultaneously postpone ageing and increase Darwinian fitness. Here we show that reducing evolutionarily conserved insulin/IGF-1 nutrient-sensing signalling via daf-2 RNA interference (RNAi) fulfils this prediction in Caenorhabditis elegans nematodes. 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 had higher Darwinian fitness across three different genotypes. Thus, reduced nutrient-sensing signalling in adulthood improves both parental longevity and offspring quality supporting the emerging view that sub-optimal gene expression in late-life lies at the heart of ageing.