Anthony Lagnado
Neutrophils induce paracrine telomere dysfunction and senescence in ROS‐dependent manner
Lagnado, Anthony; Leslie, Jack; Ruchaud‐Sparagano, Marie‐Helene; Victorelli, Stella; Hirsova, Petra; Ogrodnik, Mikolaj; Collins, Amy L; Vizioli, Maria Grazia; Habiballa, Leena; Saretzki, Gabriele; Evans, Shane A; Salmonowicz, Hanna; Hruby, Adam; Geh, Daniel; Pavelko, Kevin D; Dolan, David; Reeves, Helen L; Grellscheid, Sushma; Wilson, Colin H; Pandanaboyana, Sanjay; Doolittle, Madison; Zglinicki, Thomas; Oakley, Fiona; Gallage, Suchira; Wilson, Caroline L; Birch, Jodie; Carroll, Bernadette; Chapman, James; Heikenwalder, Mathias; Neretti, Nicola; Khosla, Sundeep; Masuda, Claudio Akio; Tchkonia, Tamar; Kirkland, James L; Jurk, Diana; Mann, Derek A; Passos, João F
Authors
Jack Leslie
Marie‐Helene Ruchaud‐Sparagano
Stella Victorelli
Petra Hirsova
Mikolaj Ogrodnik
Amy L Collins
Maria Grazia Vizioli
Leena Habiballa
Gabriele Saretzki
Shane A Evans
Hanna Salmonowicz
Adam Hruby
Daniel Geh
Kevin D Pavelko
David Dolan
Helen L Reeves
Professor Sushma Grellscheid s.n.grellscheid@durham.ac.uk
Professor
Colin H Wilson
Sanjay Pandanaboyana
Madison Doolittle
Thomas Zglinicki
Fiona Oakley
Suchira Gallage
Caroline L Wilson
Jodie Birch
Bernadette Carroll
James Chapman
Mathias Heikenwalder
Nicola Neretti
Sundeep Khosla
Claudio Akio Masuda
Tamar Tchkonia
James L Kirkland
Diana Jurk
Derek A Mann
João F Passos
Abstract
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.
Journal Article Type | Article |
---|---|
Acceptance Date | Feb 15, 2021 |
Online Publication Date | Mar 25, 2021 |
Publication Date | May 3, 2021 |
Deposit Date | Nov 12, 2021 |
Publicly Available Date | Nov 12, 2021 |
Journal | The EMBO Journal |
Print ISSN | 0261-4189 |
Electronic ISSN | 1460-2075 |
Publisher | EMBO Press |
Peer Reviewed | Peer Reviewed |
Volume | 40 |
Issue | 9 |
Article Number | e106048 |
DOI | https://doi.org/10.15252/embj.2020106048 |
Public URL | https://durham-repository.worktribe.com/output/1223360 |
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Publisher Licence URL
http://creativecommons.org/licenses/by/4.0/
Copyright Statement
© 2021 The Authors. Published under the terms of the CC BY 4.0 license
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