Cost-free lifespan extension via optimisation of gene expression in adulthood supports the developmental theory of ageing

Abstract

Classic theory upholds that energy trade-offs between reproduction and somatic maintenance underpin the evolution of ageing and lifespan. In contrast, the developmental theory of ageing (DTA) suggests that organismal senescence is caused by dysregulated gene expression in adulthood due to decline in selection gradients with age. The DTA predicts that age-specific optimisation of gene expression can improve survival without fitness costs. Here we investigated consequences for survival, reproduction, egg size and fitness of early-life, adulthood and post-reproductive onset of RNAi knockdown of five well-described "longevity" genes involved in key biological processes in Caenorhabditis elegans nematodes: nutrient-sensing signalling via insulin/IGF-1 (age-1) and target-of-rapamycin (raga-1) pathways, global protein synthesis (ifg-1), global protein synthesis in somatic cells (ife-2) and mitochondrial respiration (nuo-6). Downregulation of these genes in adulthood and/or during post-reproductive period improves survival, while there was little evidence for a link between impaired reproduction and extended lifespan. Our findings demonstrate that hyper-function of diverse physiological processes after sexual maturation is detrimental for survival. Therefore, optimisation of gene expression in adult organisms can ameliorate ageing and increase fitness.