Ageing as “early-life inertia”: Disentangling life-history trade-offs along a lifetime of an individual

Abstract

The theory that ageing evolves because of competitive resource allocation between the soma and the germline has been challenged by studies showing that somatic maintenance can be improved without impairing reproduction. However, it has been suggested that cost‐free improvement in somatic maintenance is possible only under a narrow range of benign conditions. Here, we show that experimental downregulation of insulin/IGF‐1 signaling (IIS) in C. elegans nematodes, a robustly reproducible life span‐ and health span‐extending treatment, reduces fitness in a complex variable environment when initiated during development but does not reduce fitness when initiated in adulthood. Thus, our results show that the costs and benefits of reduced IIS can be uncoupled when organisms inhabit variable environments, and, therefore, do not provide support for the resource allocation theory. Our findings support the theory that the force of natural selection on gene expression in evolutionarily conserved signaling pathways that shape life‐history traits declines after the onset of reproduction resulting in organismal senescence.

Multigenerational downregulation of insulin/IGF-1 signalling in adulthood improves lineage survival, reproduction, and fitness inC. eleganssupporting the developmental theory of ageing

“…S1). This is in agreement with previous work that showed daf-2 RNAi in adult N2 C. elegans did not reduce lambda fitness under a variable environment of light and temperature stress 28 . Extinction results did not differ significantly between two independent experimental blocks (coxph, z=-0.942, p=0.346; Fig.…”

“…4a). The relatively modest degree of daf-2 downregulation in the spontaneous MA lines for N2, and particularly for hrde-1 mutants, in comparison to the 50% knockdown of daf-2 expression from adulthood daf-2 RNAi found in previous work on Day 2 N2 adults 28 , could be due to an interaction between RNAi knockdown and genetic background, or a possible 'acclimatisation' to the multigenerational application of daf-2 RNAi in adulthood, but the exact reasons would require further investigation.…”

“…A sample from all eight MA treatments above that had been frozen at generation 20 were used (mean n= 6 MA lines per treatment, with mean n=3 individual worms per MA line; Table S1). Previous work has shown that adulthood daf-2 RNAi reduces daf-2 expression in Day 2 N2 adults by 50%, relative to controls 28 , equivalent to the first generation of MA. The aim was to test the degree of daf-2 knockdown after 20 generations of daf-2 RNAi and MA in both N2 and hrde-1 mutant backgrounds.…”

“…Mutations that reduce the function of daf-2 gene in C. elegans, the homologue of human insulin/IGF-1 receptor, increase lifespan and reduce fitness 41 . However, previous work showed that reducing IIS in adulthood via daf-2 RNA interference (RNAi) knockdown in a single generation increases lifespan without a cost to offspring number 19 , quality 20 or fitness in variable environments 28 . It is possible, however, that multi-generational daf-2 knockdown will expose a hidden cost to offspring number and/or offspring quality via accumulation of germline mutations.…”

Ageing leads to nonspecific antimicrobial peptide responses in Drosophila melanogaster

“…Age-specific hyper-activation of immunity is consistent with the evolutionary theory of ageing which predicts a progressive decline in the force of natural selection with age (Williams, 1957;Hamilton, 1966)-natural selection that optimizes organismal physiology for development and reproduction early in life, can become too weak to effectively regulate the late-life performance in older individuals (Maklakov and Chapman, 2019). For example, poor regulatory mechanisms in several evolutionarily conserved signalling pathways such as insulin/ insulin-like growth factor signalling can result in suboptimal levels of gene expression in late life, with myriad negative health effects (Kenyon, 2010;Flatt and Partridge, 2018;Carlsson et al, 2021). Such changes in conserved signalling pathways might also interfere with the optimal induction and regulation of costly immune pathways in aged individuals.…”