The senescent bystander effect is caused by ROS-activated NF-κB signalling.
Mech Ageing Dev
; 170: 30-36, 2018 03.
Article
in En
| MEDLINE
| ID: mdl-28837845
ABSTRACT
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
DNA Damage
/
NF-kappa B
/
Cellular Senescence
/
Reactive Oxygen Species
/
Bystander Effect
/
Fibroblasts
Limits:
Humans
Language:
En
Journal:
Mech Ageing Dev
Year:
2018
Document type:
Article
Affiliation country:
United kingdom