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 rectangularisation (steepening) or triangularisation (flattening) of survival curves. These two demographic changes, particularly rectangularisation, 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 rectangularisation results from healthspan expansion in short-lived population members, whereas triangularisation from healthspan and morbidity expansion in long-lived population members. Interestingly, rectangularisation and triangularisation respectively decrease and increase inter-individual variation in the ageing process, and the mode of life-extension that occurs depends on levels of existing variation. Notably, triangularisation was more effective at extending lifespan without morbidity expansion. Analysis of fruit fly and mouse data show that these biological determinants of the Strehler-Mildvan correlation are also largely evolutionarily conserved.