Senescence evolution under the catastrophic accumulation of deleterious mutations.

For aging to evolve, selection against mortality must decrease with age. This prevailing view in the evolutionary theory of senescence posits that mutations with deleterious effects happening late in life-when purging selection is weak-may become fixed via genetic drift in the germline, and produce a senescent phenotype. Theory, however, has focused primarily on growing populations and the fate of single deleterious mutations. In a mathematical model, we demonstrate that relaxing both of these simplifying assumptions leads to unrealistic outcomes. In density-regulated populations, previously fixed deleterious mutations should promote the fixation of other deleterious mutations that lead to senescence at ever younger ages, until death necessarily occurs at sexual maturity. This sequential fixation of deleterious mutations is not promoted by a decrease in population size, but is due to a change in the strength of selection. In an individual-based model, we also show that such evolutionary dynamics should lead to the extinction of most populations. Our models therefore make rather unrealistic predictions, underlining the need for a reappraisal of current theories. In this respect, we have further assumed in our models that the deleterious effects of mutations can only occur at certain ages, marked, for instance, by somatic or physiological changes. Under this condition, we show that the catastrophic accumulation of deleterious mutations in the germline can stop. This new finding emphasizes the importance of investigating somatic factors, as well as other mechanisms underlying the deleterious effects of mutations, to understand senescence evolution. More generally, our model therefore establishes that patterns of senescence in nature depend not only on the decrease in selection strength with age but also on any mechanism that stops the catastrophic accumulation of mutations.

Germline mutation rate is elevated in young and old parents in Caenorhabditis remanei.

The effect of parental age on germline mutation rate across generations is not fully understood. While some studies report a positive linear relationship of mutation rate with increasing age, others suggest that mutation rate varies with age but not in a linear fashion. We investigated the effect of parental age on germline mutations by generating replicated mutation accumulation lines in Caenorhabditis remanei at three parental ages ("Young T1" [Day 1], "Peak T2" [Day 2], and "Old T5" [Day 5] parents). We conducted whole-genome resequencing and variant calling to compare differences in mutation rates after three generations of mutation accumulation. We found that Peak T2 lines had an overall reduced mutation rate compared to Young T1 and Old T5 lines, but this pattern of the effect varied depending on the variant impact. Specifically, we found no high-impact variants in Peak T2 lines, and modifiers and up- and downstream gene variants were less frequent in these lines. These results suggest that animals at the peak of reproduction have better DNA maintenance and repair compared to young and old animals. We propose that C. remanei start to reproduce before they optimize their DNA maintenance and repair, trading the benefits of earlier onset of reproduction against offspring mutation load. The increase in offspring mutation load with age likely represents germline senescence.

Late-life fitness gains and reproductive death in Cardiocondyla obscurior ants.

A key hypothesis for the occurrence of senescence is the decrease in selection strength due to the decrease in the proportion of newborns from parents attaining an advanced age - the so-called selection shadow. Strikingly, queens of social insects have long lifespans and reproductive senescence seems to be negligible. By lifelong tracking of 99 Cardiocondyla obscurior (Formicidae: Myrmicinae) ant colonies, we find that queens shift to the production of sexuals in late life regardless of their absolute lifespan or the number of workers present. Furthermore, RNAseq analyses of old queens past their peak of reproductive performance showed the development of massive pathology while queens were still fertile, leading to rapid death. We conclude that the evolution of superorganismality is accompanied by 'continuusparity,' a life history strategy that is distinct from other iteroparous and semelparous strategies across the tree of life, in that it combines continuous reproduction with a fitness peak late in life.

Gene Coexpression Network Reveals Highly Conserved, Well-Regulated Anti-Ageing Mechanisms in Old Ant Queens.

Evolutionary theories of ageing predict a reduction in selection efficiency with age, a so-called "selection shadow," due to extrinsic mortality decreasing effective population size with age. Classic symptoms of ageing include a deterioration in transcriptional regulation and protein homeostasis. Understanding how ant queens defy the trade-off between fecundity and lifespan remains a major challenge for the evolutionary theory of ageing. It has often been discussed that the low extrinsic mortality of ant queens, that are generally well protected within the nest by workers and soldiers, should reduce the selection shadow acting on old queens. We tested this by comparing strength of selection acting on genes upregulated in young and old queens of the ant, Cardiocondyla obscurior. In support of a reduced selection shadow, we find old-biased genes to be under strong purifying selection. We also analyzed a gene coexpression network (GCN) with the aim to detect signs of ageing in the form of deteriorating regulation and proteostasis. We find no evidence for ageing. In fact, we detect higher connectivity in old queens indicating increased transcriptional regulation with age. Within the GCN, we discover five highly correlated modules that are upregulated with age. These old-biased modules regulate several antiageing mechanisms such as maintenance of proteostasis, transcriptional regulation, and stress response. We observe stronger purifying selection on central hub genes of these old-biased modules compared with young-biased modules. These results indicate a lack of transcriptional ageing in old C. obscurior queens, possibly facilitated by strong selection at old age and well-regulated antiageing mechanisms.