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Senescent cell turnover slows with age providing an explanation for the Gompertz law

Author

Listed:
  • Omer Karin

    (Weizmann Institute of Science)

  • Amit Agrawal

    (Weizmann Institute of Science)

  • Ziv Porat

    (Weizmann Institute of Science)

  • Valery Krizhanovsky

    (Weizmann Institute of Science)

  • Uri Alon

    (Weizmann Institute of Science)

Abstract

A causal factor in mammalian aging is the accumulation of senescent cells (SnCs). SnCs cause chronic inflammation, and removing SnCs decelerates aging in mice. Despite their importance, turnover rates of SnCs are unknown, and their connection to aging dynamics is unclear. Here we use longitudinal SnC measurements and induction experiments to show that SnCs turn over rapidly in young mice, with a half-life of days, but slow their own removal rate to a half-life of weeks in old mice. This leads to a critical-slowing-down that generates persistent SnC fluctuations. We further demonstrate that a mathematical model, in which death occurs when fluctuating SnCs cross a threshold, quantitatively recapitulates the Gompertz law of mortality in mice and humans. The model can go beyond SnCs to explain the effects of lifespan-modulating interventions in Drosophila and C. elegans, including scaling of survival-curves and rapid effects of dietary shifts on mortality.

Suggested Citation

  • Omer Karin & Amit Agrawal & Ziv Porat & Valery Krizhanovsky & Uri Alon, 2019. "Senescent cell turnover slows with age providing an explanation for the Gompertz law," Nature Communications, Nature, vol. 10(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13192-4
    DOI: 10.1038/s41467-019-13192-4
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    Cited by:

    1. Estrada, Ernesto & Bartesaghi, Paolo, 2022. "From networked SIS model to the Gompertz function," Applied Mathematics and Computation, Elsevier, vol. 419(C).
    2. Yifan Yang & Omer Karin & Avi Mayo & Xiaohu Song & Peipei Chen & Ana L. Santos & Ariel B. Lindner & Uri Alon, 2023. "Damage dynamics and the role of chance in the timing of E. coli cell death," Nature Communications, Nature, vol. 14(1), pages 1-11, December.

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