Hwei-yen Chen

Longer Life Span Evolves under High Rates of Condition-Dependent Mortality

Aging affects nearly all organisms, but how aging evolves is still unclear. The central prediction of classic theory is that high extrinsic mortality leads to accelerated aging and shorter intrinsic life span. However, this prediction considers mortality as a random process, whereas mortality in nature is likely to be condition dependent. Therefore, the novel theory maintains that condition dependence may dramatically alter, and even reverse, the classic pattern. We present experimental evidence for the evolution of longer life span under high condition-dependent mortality. We employed an experimental evolution design, using a nematode, Caenorhabditis remanei, that allowed us to disentangle the effects of mortality rate (high versus low) and mortality source (random versus condition dependent). We observed the evolution of shorter life span under high random mortality, confirming the classic prediction. In contrast, high condition-dependent mortality led to the evolution of longer life span, supporting a key role of condition dependence in the evolution of aging. This life-span extension was not the result of a trade-off with reproduction. By simultaneously corroborating the classic results [8-10] and providing the first experimental evidence for the novel theory, our study resolves apparent contradictions in the study of aging and challenges the traditional paradigm by demonstrating that condition-environment interactions dictate the evolutionary trajectory of aging.

Why ageing stops: heterogeneity explains late-life mortality deceleration in nematodes

While ageing is commonly associated with exponential increase in mortality with age, mortality rates paradoxically decelerate late in life resulting in distinct mortality plateaus. Late-life mortality plateaus have been discovered in a broad variety of taxa, including humans, but their origin is hotly debated. One hypothesis argues that deceleration occurs because the individual probability of death stops increasing at very old ages, predicting the evolution of earlier onset of mortality plateaus under increased rate of extrinsic mortality. By contrast, heterogeneity theory suggests that mortality deceleration arises from individual differences in intrinsic lifelong robustness and predicts that variation in robustness between populations will result in differences in mortality deceleration. We used experimental evolution to directly test these predictions by independently manipulating extrinsic mortality rate (high or low) and mortality source (random death or condition-dependent) to create replicate populations of nematodes, Caenorhabditis remanei that differ in the strength of selection in late-life and in the level of lifelong robustness. Late-life mortality deceleration evolved in response to differences in mortality source when mortality rate was held constant, while there was no consistent response to differences in mortality rate. These results provide direct experimental support for the heterogeneity theory of late-life mortality deceleration.

Slow development as an evolutionary cost of long life

Summary Life-history theory predicts a trade-off between early-life fitness and life span. While the focus traditionally has been on the fecundity-life span trade-off, there are strong reasons to expect trade-offs with growth rate and/or development time. We investigated the roles of growth rate and development time in the evolution of life span in two independent selection experiments in the outcrossing nematode Caenorhabditis remanei. First, we found that selection under heat-shock leads to the evolution of increased life span without fecundity costs, but at the cost of slower development. Thereafter, the putative evolutionary links between development time, growth rate, fecundity, heat-shock resistance and life span were independently assessed in the second experiment by directly selecting for fast or slow development. This experiment confirmed our initial findings, since selection for slow development resulted in the evolution of long life span and increased heat-shock resistance. Because there were no consistent trade-offs with growth rate or fecundity, our results highlight the key role of development rate – differentiation of the somatic cells per unit of time – in the evolution of life span. Since development time is under strong selection in nature, reduced somatic maintenance resulting in shorter life span may be a widespread cost of rapid development. A lay summary is available for this article.

The worm that lived: Evolution of rapid aging under high extrinsic mortality revisited

Organisms age because of the “selection shadow”—the decline of the force of natural selection with age. Seemingly straightforward corollary of this theory is the Medawar-Williams prediction, which maintains that increased extrinsic (non-aging) mortality will result in the evolution of accelerated aging and decreased longevity. Despite its centrality to modern thinking about the ultimate causes of aging, this prediction ignores the fact that mortality is often a non-random process depending on individual condition. Increased condition-dependent mortality inescapably results in increased selection for resistance against the agent of mortality. Provided that resistance to various stressors is commonly associated with increased longevity, the evolutionary outcome is no longer certain. We recently documented this experimentally by showing that populations of Caenorhabditis remanei evolved to live shorter under high extrinsic mortality, but only when mortality was applied haphazardly. On the contrary, when extrinsic mortality was caused by heat-shock, populations experiencing the same rate of increased mortality evolved greater longevities, notwithstanding increased “selection shadow.” Intriguingly, stress-resistant and long-lived worms were also more fecund. We discuss these results in the light of recent theoretical developments, such as condition-environment interactions and hyperfunction theory of aging.

Rapamycin additively extends lifespan in short- and long-lived lines of the nematode Caenorhabditis remanei

Abstract Despite tremendous progress in finding genes that, when manipulated, affects lifespan, little is known about the genetics underlying natural variation in lifespan. While segregating genetic variants for lifespan has been notoriously difficult to find in genome‐wide association studies (GWAS), a complementary approach is to manipulate key genetic pathways in lines that differ in lifespan. If these candidate pathways are down regulated in long‐lived lines, these lines can be predicted to respond less to pharmaceutical down‐regulation of these pathways than short‐lived lines. Experimental studies have identified the nutrient‐sensing pathway TOR as a key regulator of lifespan in model organisms, and this pathway can effectively be down regulated using the drug rapamycin, which extends lifespan in all tested species. We expose short‐ and long‐lived lines of the nematode Caenorhabditis remanei to rapamycin, and investigate if long‐lived lines, which are hypothesized to already have down‐regulated TOR signaling, respond less to rapamycin. We found no interaction between line and rapamycin treatment, since rapamycin extended lifespan independent of the intrinsic lifespan of the lines. This shows that rapamycin is equally effective on long and short‐lived lines, and suggests that the evolution of long life may involve more factors that down‐regulation of TOR. HighlightsRapamycin exposure extends lifespan across organisms by down‐regulating TOR.If long‐lived individuals have reduced TOR signaling, rapamycin may be less effective.Nematode lines differing in lifespan responded equally to rapamycin exposure.Rapamycin thus extends lifespan broadly in all individuals.This suggests that natural variation in lifespan involves more than TOR signaling.

Survival: matricide censored

Survival of development-selected lines. Worms dying of matricide are censored in this dataset.

Age-specific reproduction and size - males

Age-specific size and reproduction for development-selected males. Note that traits were not measured every day.