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

Abstract

End of life is characterized by a phase of rapid physiological decline and high morbidity, phenotypically observed as the "Smurf" phase in Drosophila, 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 consistent with 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.