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.

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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

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article

Dynamics of the end-of-life phase explained by the saturating removal model

Glen Pridham, Uri Alon, Naveh Raz, Michael Rera
bioRxiv (Cold Spring Harbor Laboratory)
Genetics, Aging, and Longevity in Model Organisms
article

Dynamics of the end-of-life phase explained by the saturating removal model

Glen Pridham, Uri Alon, Naveh Raz, Michael Rera
article en

Abstract

, 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.

bioRxiv (Cold Spring Harbor Laboratory)
Centre National de la Recherche Scientifique (FR), Université Paris Cité (FR), Unit of Functional and Adaptive Biology (FR), Weizmann Institute of Science (IL)
Weizmann Institute of Science, National Institute on Aging
Openalex Percentile: Top 21%
Genetics, Aging, and Longevity in Model Organisms
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