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

Authors :
Pastor-Fernández A
Bertos AR
Sierra-Ramírez A
Del Moral-Salmoral J
Merino J
de Ávila AI
Olagüe C
Villares R
González-Aseguinolaza G
Rodríguez MÁ
Fresno M
Gironés N
Bustos M
Smerdou C
Fernandez-Marcos PJ
von Kobbe C
Source :
Aging cell [Aging Cell] 2023 Mar; Vol. 22 (3), pp. e13771. Date of Electronic Publication: 2023 Jan 26.
Publication Year :
2023

Abstract

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.<br /> (© 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Details

Language :
English
ISSN :
1474-9726
Volume :
22
Issue :
3
Database :
MEDLINE
Journal :
Aging cell
Publication Type :
Academic Journal
Accession number :
36704839
Full Text :
https://doi.org/10.1111/acel.13771