Survival curve steepening and flattening reflect evolutionarily conserved changes in the variability of aging

Abstract

As global human life expectancy continues to rise, accompanying increases in healthspan that prevent morbidity expansion become increasingly imperative. Population lifespan can increase in distinct ways, for instance through rectangularization (steepening) or triangularization (flattening) of survival curves. These two demographic changes, particularly rectangularization, occur frequently across human and model organism populations, yet their biological determinants and effects on healthspan and morbidity are largely unknown. Notably, these modes of life-extension occur when parameters of the Gompertz mortality model (capturing exponential age-increases in mortality rate) change inversely, a widely-reported phenomenon known as the Strehler-Mildvan correlation - whose biological basis also remains unexplained. We therefore investigated longitudinal health, morbidity and lifespan in 30 Caenorhabditis elegans cohorts using multiple life-extension protocols. We report that survival curve rectangularization results from healthspan expansion in short-lived population members, whereas triangularization (which primarily extends the curve tail) from healthspan and morbidity expansion in long-lived population members. Interestingly, rectangularization and triangularization respectively decrease and increase inter-individual variation in the aging process, and the mode of life-extension that occurs depends on levels of existing variation. Notably, triangularization was more effective at extending lifespan without morbidity expansion. Analysis of fruit fly and mouse data show that these biodemographic dynamics are also largely evolutionarily conserved.