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

Omer Karin, Amit Agrawal, Ziv Porat, Valery Krizhanovsky () and Uri Alon ()
Additional contact information
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

Nature Communications, 2019, vol. 10, issue 1, 1-9

Abstract: 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.

Date: 2019
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/s41467-019-13192-4 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13192-4

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-13192-4

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().