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Neutrophils induce paracrine telomere dysfunction and senescence in ROS‐dependent manner
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 nu...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8090854/ https://www.ncbi.nlm.nih.gov/pubmed/33764576 http://dx.doi.org/10.15252/embj.2020106048 |
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author | 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 von 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 |
author_facet | 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 von 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 |
author_sort | Lagnado, Anthony |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8090854 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-80908542021-05-14 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 von 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 EMBO J Articles 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. John Wiley and Sons Inc. 2021-03-25 2021-05-03 /pmc/articles/PMC8090854/ /pubmed/33764576 http://dx.doi.org/10.15252/embj.2020106048 Text en © 2021 The Authors. Published under the terms of the CC BY 4.0 license https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Articles 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 von 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 Neutrophils induce paracrine telomere dysfunction and senescence in ROS‐dependent manner |
title | Neutrophils induce paracrine telomere dysfunction and senescence in ROS‐dependent manner |
title_full | Neutrophils induce paracrine telomere dysfunction and senescence in ROS‐dependent manner |
title_fullStr | Neutrophils induce paracrine telomere dysfunction and senescence in ROS‐dependent manner |
title_full_unstemmed | Neutrophils induce paracrine telomere dysfunction and senescence in ROS‐dependent manner |
title_short | Neutrophils induce paracrine telomere dysfunction and senescence in ROS‐dependent manner |
title_sort | neutrophils induce paracrine telomere dysfunction and senescence in ros‐dependent manner |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8090854/ https://www.ncbi.nlm.nih.gov/pubmed/33764576 http://dx.doi.org/10.15252/embj.2020106048 |
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