Neutrophils induce paracrine telomere dysfunction and senescence in ROS-dependent manner.
Acute Lung Injury
/ chemically induced
Animals
Carbon Tetrachloride
/ adverse effects
Cell Line
Cellular Senescence
Coculture Techniques
Disease Models, Animal
Female
Fibroblasts
/ cytology
Humans
Male
Mice
Neutrophils
/ cytology
Oxidative Stress
Paracrine Communication
Reactive Oxygen Species
/ metabolism
Telomere Shortening
aging
neutrophils
senescence
telomeres
Journal
The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664
Informations de publication
Date de publication:
03 05 2021
03 05 2021
Historique:
revised:
09
02
2021
received:
24
06
2020
accepted:
15
02
2021
pubmed:
26
3
2021
medline:
5
11
2021
entrez:
25
3
2021
Statut:
ppublish
Résumé
Cellular senescence is characterized by an irreversible cell cycle arrest as well as a pro-inflammatory phenotype, thought to contribute to aging and age-related diseases. Neutrophils have essential roles in inflammatory responses; however, in certain contexts their abundance is associated with a number of age-related diseases, including liver disease. The relationship between neutrophils and cellular senescence is not well understood. Here, we show that telomeres in non-immune cells are highly susceptible to oxidative damage caused by neighboring neutrophils. Neutrophils cause telomere dysfunction both in vitro and ex vivo in a ROS-dependent manner. In a mouse model of acute liver injury, depletion of neutrophils reduces telomere dysfunction and senescence. Finally, we show that senescent cells mediate the recruitment of neutrophils to the aged liver and propose that this may be a mechanism by which senescence spreads to surrounding cells. Our results suggest that interventions that counteract neutrophil-induced senescence may be beneficial during aging and age-related disease.
Identifiants
pubmed: 33764576
doi: 10.15252/embj.2020106048
pmc: PMC8090854
doi:
Substances chimiques
Reactive Oxygen Species
0
Carbon Tetrachloride
CL2T97X0V0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e106048Subventions
Organisme : Medical Research Council
ID : MR/K001949/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0900535
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : R01 AG050582
Pays : United States
Organisme : NIA NIH HHS
ID : R37 AG013925
Pays : United States
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/K017314/1
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : R01 AG068182
Pays : United States
Organisme : Medical Research Council
ID : MR/K0019494/1
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 26813
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : T32 AG049672
Pays : United States
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/L502066/1
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : P01 AG062413
Pays : United States
Organisme : National Centre for the Replacement, Refinement and Reduction of Animals in Research
ID : NC/K000748/1
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C18342/A23390
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/R023026/1
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : R01 AG068048
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK084567
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2021 The Authors. Published under the terms of the CC BY 4.0 license.
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