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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

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Authors

Anthony Lagnado

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

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.

Citation

Lagnado, A., Leslie, J., Ruchaud‐Sparagano, M., Victorelli, S., Hirsova, P., Ogrodnik, M., …Passos, J. F. (2021). Neutrophils induce paracrine telomere dysfunction and senescence in ROS‐dependent manner. The EMBO Journal, 40(9), Article e106048. https://doi.org/10.15252/embj.2020106048

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 Mar 28, 2024
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

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