Cargando…

Removal of senescent cells reduces the viral load and attenuates pulmonary and systemic inflammation in SARS-CoV-2-infected, aged hamsters

Older age is one of the strongest risk factors for severe COVID-19. In this study, we determined whether age-associated cellular senescence contributes to the severity of experimental COVID-19. Aged golden hamsters accumulate senescent cells in the lungs, and the senolytic drug ABT-263, a BCL-2 inhi...

Descripción completa

Detalles Bibliográficos
Autores principales: Delval, Lou, Hantute-Ghesquier, Aline, Sencio, Valentin, Flaman, Jean Michel, Robil, Cyril, Angulo, Fabiola Silva, Lipskaia, Larissa, Çobanoğlu, Ozmen, Lacoste, Anne-Sophie, Machelart, Arnaud, Danneels, Adeline, Corbin, Mathieu, Deruyter, Lucie, Heumel, Séverine, Idziorek, Thierry, Séron, Karin, Sauve, Florent, Bongiovanni, Antonino, Prévot, Vincent, Wolowczuk, Isabelle, Belouzard, Sandrine, Saliou, Jean-Michel, Gosset, Philippe, Bernard, David, Rouillé, Yves, Adnot, Serge, Duterque-Coquillaud, Martine, Trottein, François
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group US 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10353934/
https://www.ncbi.nlm.nih.gov/pubmed/37414987
http://dx.doi.org/10.1038/s43587-023-00442-w
_version_ 1785074810199474176
author Delval, Lou
Hantute-Ghesquier, Aline
Sencio, Valentin
Flaman, Jean Michel
Robil, Cyril
Angulo, Fabiola Silva
Lipskaia, Larissa
Çobanoğlu, Ozmen
Lacoste, Anne-Sophie
Machelart, Arnaud
Danneels, Adeline
Corbin, Mathieu
Deruyter, Lucie
Heumel, Séverine
Idziorek, Thierry
Séron, Karin
Sauve, Florent
Bongiovanni, Antonino
Prévot, Vincent
Wolowczuk, Isabelle
Belouzard, Sandrine
Saliou, Jean-Michel
Gosset, Philippe
Bernard, David
Rouillé, Yves
Adnot, Serge
Duterque-Coquillaud, Martine
Trottein, François
author_facet Delval, Lou
Hantute-Ghesquier, Aline
Sencio, Valentin
Flaman, Jean Michel
Robil, Cyril
Angulo, Fabiola Silva
Lipskaia, Larissa
Çobanoğlu, Ozmen
Lacoste, Anne-Sophie
Machelart, Arnaud
Danneels, Adeline
Corbin, Mathieu
Deruyter, Lucie
Heumel, Séverine
Idziorek, Thierry
Séron, Karin
Sauve, Florent
Bongiovanni, Antonino
Prévot, Vincent
Wolowczuk, Isabelle
Belouzard, Sandrine
Saliou, Jean-Michel
Gosset, Philippe
Bernard, David
Rouillé, Yves
Adnot, Serge
Duterque-Coquillaud, Martine
Trottein, François
author_sort Delval, Lou
collection PubMed
description Older age is one of the strongest risk factors for severe COVID-19. In this study, we determined whether age-associated cellular senescence contributes to the severity of experimental COVID-19. Aged golden hamsters accumulate senescent cells in the lungs, and the senolytic drug ABT-263, a BCL-2 inhibitor, depletes these cells at baseline and during SARS-CoV-2 infection. Relative to young hamsters, aged hamsters had a greater viral load during the acute phase of infection and displayed higher levels of sequelae during the post-acute phase. Early treatment with ABT-263 lowered pulmonary viral load in aged (but not young) animals, an effect associated with lower expression of ACE2, the receptor for SARS-CoV-2. ABT-263 treatment also led to lower pulmonary and systemic levels of senescence-associated secretory phenotype factors and to amelioration of early and late lung disease. These data demonstrate the causative role of age-associated pre-existing senescent cells on COVID-19 severity and have clear clinical relevance.
format Online
Article
Text
id pubmed-10353934
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Nature Publishing Group US
record_format MEDLINE/PubMed
spelling pubmed-103539342023-07-20 Removal of senescent cells reduces the viral load and attenuates pulmonary and systemic inflammation in SARS-CoV-2-infected, aged hamsters Delval, Lou Hantute-Ghesquier, Aline Sencio, Valentin Flaman, Jean Michel Robil, Cyril Angulo, Fabiola Silva Lipskaia, Larissa Çobanoğlu, Ozmen Lacoste, Anne-Sophie Machelart, Arnaud Danneels, Adeline Corbin, Mathieu Deruyter, Lucie Heumel, Séverine Idziorek, Thierry Séron, Karin Sauve, Florent Bongiovanni, Antonino Prévot, Vincent Wolowczuk, Isabelle Belouzard, Sandrine Saliou, Jean-Michel Gosset, Philippe Bernard, David Rouillé, Yves Adnot, Serge Duterque-Coquillaud, Martine Trottein, François Nat Aging Article Older age is one of the strongest risk factors for severe COVID-19. In this study, we determined whether age-associated cellular senescence contributes to the severity of experimental COVID-19. Aged golden hamsters accumulate senescent cells in the lungs, and the senolytic drug ABT-263, a BCL-2 inhibitor, depletes these cells at baseline and during SARS-CoV-2 infection. Relative to young hamsters, aged hamsters had a greater viral load during the acute phase of infection and displayed higher levels of sequelae during the post-acute phase. Early treatment with ABT-263 lowered pulmonary viral load in aged (but not young) animals, an effect associated with lower expression of ACE2, the receptor for SARS-CoV-2. ABT-263 treatment also led to lower pulmonary and systemic levels of senescence-associated secretory phenotype factors and to amelioration of early and late lung disease. These data demonstrate the causative role of age-associated pre-existing senescent cells on COVID-19 severity and have clear clinical relevance. Nature Publishing Group US 2023-07-06 2023 /pmc/articles/PMC10353934/ /pubmed/37414987 http://dx.doi.org/10.1038/s43587-023-00442-w Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Delval, Lou
Hantute-Ghesquier, Aline
Sencio, Valentin
Flaman, Jean Michel
Robil, Cyril
Angulo, Fabiola Silva
Lipskaia, Larissa
Çobanoğlu, Ozmen
Lacoste, Anne-Sophie
Machelart, Arnaud
Danneels, Adeline
Corbin, Mathieu
Deruyter, Lucie
Heumel, Séverine
Idziorek, Thierry
Séron, Karin
Sauve, Florent
Bongiovanni, Antonino
Prévot, Vincent
Wolowczuk, Isabelle
Belouzard, Sandrine
Saliou, Jean-Michel
Gosset, Philippe
Bernard, David
Rouillé, Yves
Adnot, Serge
Duterque-Coquillaud, Martine
Trottein, François
Removal of senescent cells reduces the viral load and attenuates pulmonary and systemic inflammation in SARS-CoV-2-infected, aged hamsters
title Removal of senescent cells reduces the viral load and attenuates pulmonary and systemic inflammation in SARS-CoV-2-infected, aged hamsters
title_full Removal of senescent cells reduces the viral load and attenuates pulmonary and systemic inflammation in SARS-CoV-2-infected, aged hamsters
title_fullStr Removal of senescent cells reduces the viral load and attenuates pulmonary and systemic inflammation in SARS-CoV-2-infected, aged hamsters
title_full_unstemmed Removal of senescent cells reduces the viral load and attenuates pulmonary and systemic inflammation in SARS-CoV-2-infected, aged hamsters
title_short Removal of senescent cells reduces the viral load and attenuates pulmonary and systemic inflammation in SARS-CoV-2-infected, aged hamsters
title_sort removal of senescent cells reduces the viral load and attenuates pulmonary and systemic inflammation in sars-cov-2-infected, aged hamsters
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10353934/
https://www.ncbi.nlm.nih.gov/pubmed/37414987
http://dx.doi.org/10.1038/s43587-023-00442-w
work_keys_str_mv AT delvallou removalofsenescentcellsreducestheviralloadandattenuatespulmonaryandsystemicinflammationinsarscov2infectedagedhamsters
AT hantuteghesquieraline removalofsenescentcellsreducestheviralloadandattenuatespulmonaryandsystemicinflammationinsarscov2infectedagedhamsters
AT senciovalentin removalofsenescentcellsreducestheviralloadandattenuatespulmonaryandsystemicinflammationinsarscov2infectedagedhamsters
AT flamanjeanmichel removalofsenescentcellsreducestheviralloadandattenuatespulmonaryandsystemicinflammationinsarscov2infectedagedhamsters
AT robilcyril removalofsenescentcellsreducestheviralloadandattenuatespulmonaryandsystemicinflammationinsarscov2infectedagedhamsters
AT angulofabiolasilva removalofsenescentcellsreducestheviralloadandattenuatespulmonaryandsystemicinflammationinsarscov2infectedagedhamsters
AT lipskaialarissa removalofsenescentcellsreducestheviralloadandattenuatespulmonaryandsystemicinflammationinsarscov2infectedagedhamsters
AT cobanogluozmen removalofsenescentcellsreducestheviralloadandattenuatespulmonaryandsystemicinflammationinsarscov2infectedagedhamsters
AT lacosteannesophie removalofsenescentcellsreducestheviralloadandattenuatespulmonaryandsystemicinflammationinsarscov2infectedagedhamsters
AT machelartarnaud removalofsenescentcellsreducestheviralloadandattenuatespulmonaryandsystemicinflammationinsarscov2infectedagedhamsters
AT danneelsadeline removalofsenescentcellsreducestheviralloadandattenuatespulmonaryandsystemicinflammationinsarscov2infectedagedhamsters
AT corbinmathieu removalofsenescentcellsreducestheviralloadandattenuatespulmonaryandsystemicinflammationinsarscov2infectedagedhamsters
AT deruyterlucie removalofsenescentcellsreducestheviralloadandattenuatespulmonaryandsystemicinflammationinsarscov2infectedagedhamsters
AT heumelseverine removalofsenescentcellsreducestheviralloadandattenuatespulmonaryandsystemicinflammationinsarscov2infectedagedhamsters
AT idziorekthierry removalofsenescentcellsreducestheviralloadandattenuatespulmonaryandsystemicinflammationinsarscov2infectedagedhamsters
AT seronkarin removalofsenescentcellsreducestheviralloadandattenuatespulmonaryandsystemicinflammationinsarscov2infectedagedhamsters
AT sauveflorent removalofsenescentcellsreducestheviralloadandattenuatespulmonaryandsystemicinflammationinsarscov2infectedagedhamsters
AT bongiovanniantonino removalofsenescentcellsreducestheviralloadandattenuatespulmonaryandsystemicinflammationinsarscov2infectedagedhamsters
AT prevotvincent removalofsenescentcellsreducestheviralloadandattenuatespulmonaryandsystemicinflammationinsarscov2infectedagedhamsters
AT wolowczukisabelle removalofsenescentcellsreducestheviralloadandattenuatespulmonaryandsystemicinflammationinsarscov2infectedagedhamsters
AT belouzardsandrine removalofsenescentcellsreducestheviralloadandattenuatespulmonaryandsystemicinflammationinsarscov2infectedagedhamsters
AT salioujeanmichel removalofsenescentcellsreducestheviralloadandattenuatespulmonaryandsystemicinflammationinsarscov2infectedagedhamsters
AT gossetphilippe removalofsenescentcellsreducestheviralloadandattenuatespulmonaryandsystemicinflammationinsarscov2infectedagedhamsters
AT bernarddavid removalofsenescentcellsreducestheviralloadandattenuatespulmonaryandsystemicinflammationinsarscov2infectedagedhamsters
AT rouilleyves removalofsenescentcellsreducestheviralloadandattenuatespulmonaryandsystemicinflammationinsarscov2infectedagedhamsters
AT adnotserge removalofsenescentcellsreducestheviralloadandattenuatespulmonaryandsystemicinflammationinsarscov2infectedagedhamsters
AT duterquecoquillaudmartine removalofsenescentcellsreducestheviralloadandattenuatespulmonaryandsystemicinflammationinsarscov2infectedagedhamsters
AT trotteinfrancois removalofsenescentcellsreducestheviralloadandattenuatespulmonaryandsystemicinflammationinsarscov2infectedagedhamsters