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Treatment with the senolytics dasatinib/quercetin reduces SARS‐CoV‐2‐related mortality in mice

The enormous societal impact of the ongoing COVID‐19 pandemic has been particularly harsh for some social groups, such as the elderly. Recently, it has been suggested that senescent cells could play a central role in pathogenesis by exacerbating the pro‐inflammatory immune response against SARS‐CoV‐...

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Autores principales: Pastor‐Fernández, Andrés, Bertos, Antonio R., Sierra‐Ramírez, Arantzazu, del Moral‐Salmoral, Javier, Merino, Javier, de Ávila, Ana I., Olagüe, Cristina, Villares, Ricardo, González‐Aseguinolaza, Gloria, Rodríguez, María Ángeles, Fresno, Manuel, Gironés, Nuria, Bustos, Matilde, Smerdou, Cristian, Fernandez‐Marcos, Pablo Jose, von Kobbe, Cayetano
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10014049/
https://www.ncbi.nlm.nih.gov/pubmed/36704839
http://dx.doi.org/10.1111/acel.13771
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author Pastor‐Fernández, Andrés
Bertos, Antonio R.
Sierra‐Ramírez, Arantzazu
del Moral‐Salmoral, Javier
Merino, Javier
de Ávila, Ana I.
Olagüe, Cristina
Villares, Ricardo
González‐Aseguinolaza, Gloria
Rodríguez, María Ángeles
Fresno, Manuel
Gironés, Nuria
Bustos, Matilde
Smerdou, Cristian
Fernandez‐Marcos, Pablo Jose
von Kobbe, Cayetano
author_facet Pastor‐Fernández, Andrés
Bertos, Antonio R.
Sierra‐Ramírez, Arantzazu
del Moral‐Salmoral, Javier
Merino, Javier
de Ávila, Ana I.
Olagüe, Cristina
Villares, Ricardo
González‐Aseguinolaza, Gloria
Rodríguez, María Ángeles
Fresno, Manuel
Gironés, Nuria
Bustos, Matilde
Smerdou, Cristian
Fernandez‐Marcos, Pablo Jose
von Kobbe, Cayetano
author_sort Pastor‐Fernández, Andrés
collection PubMed
description The enormous societal impact of the ongoing COVID‐19 pandemic has been particularly harsh for some social groups, such as the elderly. Recently, it has been suggested that senescent cells could play a central role in pathogenesis by exacerbating the pro‐inflammatory immune response against SARS‐CoV‐2. Therefore, the selective clearance of senescent cells by senolytic drugs may be useful as a therapy to ameliorate the symptoms of COVID‐19 in some cases. Using the established COVID‐19 murine model K18‐hACE2, we demonstrated that a combination of the senolytics dasatinib and quercetin (D/Q) significantly reduced SARS‐CoV‐2‐related mortality, delayed its onset, and reduced the number of other clinical symptoms. The increase in senescent markers that we detected in the lungs in response to SARS‐CoV‐2 may be related to the post‐COVID‐19 sequelae described to date. These results place senescent cells as central targets for the treatment of COVID‐19, and make D/Q a new and promising therapeutic tool.
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spelling pubmed-100140492023-03-15 Treatment with the senolytics dasatinib/quercetin reduces SARS‐CoV‐2‐related mortality in mice Pastor‐Fernández, Andrés Bertos, Antonio R. Sierra‐Ramírez, Arantzazu del Moral‐Salmoral, Javier Merino, Javier de Ávila, Ana I. Olagüe, Cristina Villares, Ricardo González‐Aseguinolaza, Gloria Rodríguez, María Ángeles Fresno, Manuel Gironés, Nuria Bustos, Matilde Smerdou, Cristian Fernandez‐Marcos, Pablo Jose von Kobbe, Cayetano Aging Cell Research Articles The enormous societal impact of the ongoing COVID‐19 pandemic has been particularly harsh for some social groups, such as the elderly. Recently, it has been suggested that senescent cells could play a central role in pathogenesis by exacerbating the pro‐inflammatory immune response against SARS‐CoV‐2. Therefore, the selective clearance of senescent cells by senolytic drugs may be useful as a therapy to ameliorate the symptoms of COVID‐19 in some cases. Using the established COVID‐19 murine model K18‐hACE2, we demonstrated that a combination of the senolytics dasatinib and quercetin (D/Q) significantly reduced SARS‐CoV‐2‐related mortality, delayed its onset, and reduced the number of other clinical symptoms. The increase in senescent markers that we detected in the lungs in response to SARS‐CoV‐2 may be related to the post‐COVID‐19 sequelae described to date. These results place senescent cells as central targets for the treatment of COVID‐19, and make D/Q a new and promising therapeutic tool. John Wiley and Sons Inc. 2023-01-26 /pmc/articles/PMC10014049/ /pubmed/36704839 http://dx.doi.org/10.1111/acel.13771 Text en © 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd. 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 Research Articles
Pastor‐Fernández, Andrés
Bertos, Antonio R.
Sierra‐Ramírez, Arantzazu
del Moral‐Salmoral, Javier
Merino, Javier
de Ávila, Ana I.
Olagüe, Cristina
Villares, Ricardo
González‐Aseguinolaza, Gloria
Rodríguez, María Ángeles
Fresno, Manuel
Gironés, Nuria
Bustos, Matilde
Smerdou, Cristian
Fernandez‐Marcos, Pablo Jose
von Kobbe, Cayetano
Treatment with the senolytics dasatinib/quercetin reduces SARS‐CoV‐2‐related mortality in mice
title Treatment with the senolytics dasatinib/quercetin reduces SARS‐CoV‐2‐related mortality in mice
title_full Treatment with the senolytics dasatinib/quercetin reduces SARS‐CoV‐2‐related mortality in mice
title_fullStr Treatment with the senolytics dasatinib/quercetin reduces SARS‐CoV‐2‐related mortality in mice
title_full_unstemmed Treatment with the senolytics dasatinib/quercetin reduces SARS‐CoV‐2‐related mortality in mice
title_short Treatment with the senolytics dasatinib/quercetin reduces SARS‐CoV‐2‐related mortality in mice
title_sort treatment with the senolytics dasatinib/quercetin reduces sars‐cov‐2‐related mortality in mice
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10014049/
https://www.ncbi.nlm.nih.gov/pubmed/36704839
http://dx.doi.org/10.1111/acel.13771
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