Dynamics of the end-of-life phase explained by the saturating removal model
, metabolic end-of-life dysregulation in mice, and end-stage frailty in humans. Existing two-phase aging models often conceptualize this end-of-life phase as a discrete biological state. Here, we demonstrate that a continuous stochastic model of damage accumulation, the saturating removal (SR) model, captures these multi-species morbidity dynamics. By defining the end-of-life phase as a stochastic crossing of a sub-lethal damage threshold, the SR model accurately reproduces empirical end-of-life dynamics across flies, mice, and humans. The model predicts a surprising temporary reduction in hazard shortly after entering the end-of-life phase, resulting in a U-shaped hazard curve, consistent with the empirical data in all three organisms. It also correctly predicts a shortening twilight phenomenon where the mean duration of the end-of-life phase decreases the later its onset. We conclude that end-of-life dynamics are consistent with universal features of a driver of aging crossing a threshold for end-of-life morbidity and then a threshold for death.
Authors
- Glen Pridham (ORCID: https://orcid.org/0000-0001-9450-0396)
- Uri Alon (ORCID: https://orcid.org/0000-0001-6903-9956)
- Naveh Raz
- Michael Rera (ORCID: https://orcid.org/0000-0002-6574-6511)
Institutions
- Centre National de la Recherche Scientifique (FR)
- Université Paris Cité (FR)
- Unit of Functional and Adaptive Biology (FR)
- Weizmann Institute of Science (IL)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2026-04-22
- DOI
- https://doi.org/10.64898/2026.04.20.719588
- Primary Topic
- Genetics, Aging, and Longevity in Model Organisms
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Weizmann Institute of Science
- National Institute on Aging