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Dissecting primary and secondary senescence to enable new senotherapeutic strategies

journal contribution
posted on 26.07.2021, 08:46 by Tesfahun Dessale Admasu, Michael Rae, Alexandra StolzingAlexandra Stolzing
Cellular senescence is a state of stable cell cycle arrest that is known to be elicited in response to different stresses or forms of damage. Senescence limits the replication of old, damaged, and precancerous cells in the short-term but is implicated in diseases and debilities of aging due to loss of regenerative reserve and secretion of a complex combination of factors called the senescence-associated secretory phenotype (SASP). More recently, investigators have discovered that senescent cells induced by these methods (what we term “primary senescent cells”) are also capable of inducing other non-senescent cells to undergo senescence — a phenomenon we call “secondary senescence.” Secondary senescence has been demonstrated to occur via two broad types of mechanisms. First, factors in the SASP have been shown to be involved in spreading senescence; we call this phenomenon “paracrine senescence.” Second, primary senescent cells can induce senescence via an additional group of mechanisms involving cell-to-cell contacts of different types; we term this phenomenon “juxtacrine senescence.” “Secondary senescence” in our definition is thus the overarching term for both paracrine and juxtacrine senescence together. By allowing cells that are inherently small in number and incapable of replication to increase in number and possibly spread to anatomically distant locations, secondary senescence allows an initially small number of senescent cells to contribute further to age-related pathologies. We propose that understanding how primary and secondary senescent cells differ from each other and the mechanisms of their spread will enable the development of new rejuvenation therapies to target different senescent cell populations and interrupt their spread, extending human health- and potentially lifespan.

Funding

SENS Research Foundation (SRF).

History

School

  • Mechanical, Electrical and Manufacturing Engineering

Published in

Ageing Research Reviews

Volume

70

Publisher

Elsevier BV

Version

AM (Accepted Manuscript)

Rights holder

© Elsevier

Publisher statement

This paper was accepted for publication in the journal Ageing Research Reviews and the definitive published version is available at https://doi.org/10.1016/j.arr.2021.101412

Acceptance date

16/07/2021

Publication date

2021-07-21

Copyright date

2021

ISSN

1568-1637

Language

en

Depositor

Prof Alexandra Stolzing. Deposit date: 24 July 2021

Article number

101412