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Neutrophils induce paracrine telomere dysfunction and senescence in ROS‐dependent manner
Author(s) -
Lagnado Anthony,
Leslie Jack,
RuchaudSparagano MarieHelene,
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
Publication year - 2021
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2020106048
Subject(s) - medicine , gerontology
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.