Compression of morbidity by interventions that steepen the survival curve

Yifan Yang (), Avi Mayo, Tomer Levy, Naveh Raz, Ben Shenhar, Daniel F. Jarosz and Uri Alon ()
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Yifan Yang: Weizmann Institute of Science
Avi Mayo: Weizmann Institute of Science
Tomer Levy: Weizmann Institute of Science
Naveh Raz: Weizmann Institute of Science
Ben Shenhar: Weizmann Institute of Science
Daniel F. Jarosz: Stanford University School of Medicine
Uri Alon: Weizmann Institute of Science

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: Abstract Longevity research aims to extend the healthspan while minimizing the duration of disability and morbidity, known as the sickspan. Most longevity interventions in model organisms extend healthspan, but it is not known whether they compress sickspan relative to the lifespan. Here, we present a theory that predicts which interventions compress relative sickspan, based on the shape of the survival curve. Interventions such as caloric restriction that extend mean lifespan while preserving the shape of the survival curve, are predicted to extend the sickspan proportionally, without compressing it. Conversely, a subset of interventions that extend lifespan and steepen the shape of the survival curve are predicted to compress the relative sickspan. We explain this based on the saturating-removal mathematical model of aging, and present evidence from longitudinal health data in mice, Caenorhabditis elegans and Drosophila melanogaster. We apply this theory to identify potential interventions for compressing the sickspan in mice, and to combinations of longevity interventions. This approach offers potential strategies for compressing morbidity and extending healthspan.

Date: 2025
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DOI: 10.1038/s41467-025-57807-5

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