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

Abstract

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. Latelife 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.

The Williams' legacy: A critical reappraisal of his nine predictions about the evolution of senescence

“…In humans, the change in the distribution of the relative quality of individuals with age is often invoked to explain both the decreased risk of contracting diseases such as cancer once a given age threshold is reached (de Magalhães ) and the existence of a “mortality plateau” characterized by a decrease in age‐specific mortality rate at very late ages (e.g., Vaupel ; see also Chen et al. for an example in the nematode Caenorhabditis remanei ).…”

Mortality Implications of Mortality Plateaus

“…The unidentifiability of frailty models in the absence of ancillary information, though, made it impossible to differentiate between the homogeneous and the heterogeneous models. A recent article by Chen, Zajitschek, and Maklakov [15] seems to have overcome this obstacle and argues that heterogeneity explains mortality deceleration in nematodes.…”

Evolution of fixed demographic heterogeneity from a game of stable coexistence

“…The average mortality in a cohort of same-age individuals from a demographically heterogeneous population differs from the mortalities observed in cohorts from composing subpopulations (Curtsinger et al 1992;Vaupel and Carey 1993;Chen, Zajitschek, and Maklakov 2013;Vaupel and Yashin 1985). Here we show that interesting patterns of average cohort mortality can be retrieved from points inside coexistence regions like those explored in the previous section.…”

“…This is at odds with the prediction from classical evolutionary theory of senescence, which predicts increasing mortality with age (Hamilton 1966;Charlesworth and Partridge 1997). However, the presence of subcohorts all experiencing a steady increase in mortality with age but at different rates can explain this effect (Curtsinger et al 1992;Vaupel and Carey 1993;Chen, Zajitschek, and Maklakov 2013), as the aggregate cohort may not display a monotonically increasing mortality with age in that case (Vaupel and Yashin 1985). A similar explanation can be provided based on dynamic heterogeneity (Horvitz and Tuljapurkar 2008), as well as based on some form of heterogeneity that is present at birth yet still potentially modifiable thereafter (Le Bras 1976;Yashin, Vaupel, and Iachine 1994).…”