The Strehler-Mildvan mortality correlation arises from changes in the variability of ageing

Area of Science:

• Gerontology
• Demography
• Molecular Biology

Background:

• Rising global life expectancy necessitates extending healthspan alongside lifespan.
• Population lifespan can increase via survival curve rectangularisation or triangularisation, but their biological underpinnings are unclear.
• The Strehler-Mildvan correlation, an inverse relationship in Gompertz mortality model parameters, is observed but lacks a biological explanation.

Purpose of the Study:

• To investigate the biological determinants of survival curve rectangularisation and triangularisation.
• To understand the effects of these demographic changes on healthspan and morbidity.
• To explore the evolutionary conservation of these aging patterns.

Main Methods:

• Longitudinal analysis of health, morbidity, and lifespan in 30 *Caenorhabditis elegans* cohorts.
• Application of multiple life-extension protocols.
• Analysis of corresponding data from fruit fly and mouse models.

Main Results:

• Survival curve rectangularisation is driven by healthspan expansion in shorter-lived individuals.
• Survival curve triangularisation results from healthspan and morbidity expansion in longer-lived individuals.
• Rectangularisation decreases and triangularisation increases inter-individual variation in aging; the mode depends on existing variation.
• Triangularisation was more effective at extending lifespan without morbidity expansion.

Conclusions:

• The study elucidates the distinct biological mechanisms driving survival curve rectangularisation and triangularisation.
• These findings explain the biological basis of the Strehler-Mildvan correlation.
• The identified determinants of aging patterns are evolutionarily conserved across species, including humans, fruit flies, and mice.