Cost-free lifespan extension via optimization of gene expression in adulthood aligns with the developmental theory of ageing.

Martin I Lind,Edward Ivimey-Cook,Hanne Carlsson,Alexei A Maklakov,Elizabeth M L Duxbury

doi:10.1098/rspb.2020.1728

Abstract

Ageing evolves because the force of selection on traits declines with age but the proximate causes of ageing are incompletely understood. The ‘disposable soma’ theory of ageing (DST) upholds that competitive resource allocation between reproduction and somatic maintenance underpins the evolution of ageing and lifespan. In contrast, the developmental theory of ageing (DTA) suggests that organismal senescence is caused by suboptimal gene expression in adulthood. While the DST predicts the trade-off between reproduction and lifespan, the DTA predicts that age-specific optimization of gene expression can increase lifespan without reproduction costs. Here we investigated the consequences for lifespan, reproduction, egg size and individual fitness of early-life, adulthood and post-reproductive onset of RNAi knockdown of five ‘longevity’ genes involved in key biological processes in Caenorhabditis elegans. Downregulation of these genes in adulthood and/or during post-reproductive period increases lifespan, while we found limited evidence for a link between impaired reproduction and extended lifespan. Our findings demonstrate that suboptimal gene expression in adulthood often contributes to reduced lifespan directly rather than through competitive resource allocation between reproduction and somatic maintenance. Therefore, age-specific optimization of gene expression in evolutionarily conserved signalling pathways that regulate organismal life histories can increase lifespan without fitness costs.

Highlights

The force of natural selection is maximized during pre-reproductive development but declines after sexual maturation with advancing age [1,2,3,4]
We investigated age-specific RNA interference (RNAi) effects on survival, age-specific reproduction and egg size; we used these data to determine lifetime reproductive success (LRS) and rate-sensitive individual fitness
Downregulation of age-1 across all life stages improved longevity and decreased age-specific mortality rate, but the effect became progressively weaker with increasing age of onset of the RNAi treatment; we found no indication that age-1 RNAi negatively affected LRS, egg size or individual fitness

Summary

Introduction

The force of natural selection is maximized during pre-reproductive development but declines after sexual maturation with advancing age [1,2,3,4]. Our approach was to use age-specific RNAi to downregulate the expression of these genes starting at three different stages across the life course of C. elegans: (i) newly laid egg (lifelong treatment), (ii) sexual maturity (adulthood treatment) and (iii) the end of self-fertilized reproduction ( postreproductive treatment) This approach allowed us to assess the fitness consequences of lifelong and adulthood-only downregulation of the target genes, as well as the effects of post-reproductive downregulation on survival. It is the most appropriate fitness measure when timing is important for fitness [42]

Methods

Results

Discussion