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The senescent bystander effect is caused by ROS-activated NF-κB signalling

Lookup NU author(s): Dr Glyn NelsonORCiD, Dr Olena Kucheryavenko, James Wordsworth, Professor Thomas von Zglinicki



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2017 The Authors. Cell senescence is an important driver of the ageing process. The accumulation of senescent cells in tissues is accelerated by stress signals from senescent cells that induce DNA damage and ultimately senescence in bystander cells. We examine here the interplay of senescence-associated mitochondrial dysfunction (SAMD)-driven production of reactive oxygen species (ROS) and senescence-associated secretory phenotype (SASP) in causing the bystander effect. We show that in various modes of fibroblast senescence ROS are necessary and sufficient to activate the transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), which facilitates a large part of the SASP. This ROS-NF-κB axis causes the DNA damage response in bystander cells. Cytokines IL-6 and IL-8 are major components of the pro-inflammatory SASP in senescent fibroblasts. However, their activation in senescence is only partially controlled by NF-κB, and they are thus not strong candidates as intercellular mediators of the bystander effect as mediated by the ROS-NF-κB axis.

Publication metadata

Author(s): Nelson G, Kucheryavenko O, Wordsworth J, von Zglinicki T

Publication type: Article

Publication status: Published

Journal: Mechanisms of Ageing and Development

Year: 2018

Volume: 170

Pages: 30-36

Print publication date: 01/03/2018

Online publication date: 25/08/2017

Acceptance date: 14/08/2017

Date deposited: 29/09/2017

ISSN (print): 0047-6374

ISSN (electronic): 1872-6216

Publisher: Elsevier


DOI: 10.1016/j.mad.2017.08.005


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Funder referenceFunder name
BB/K019260/1Biotechnology and Biological Sciences Research Council (BBSRC)