Treatment with the senolytics dasatinib/quercetin reduces SARS-CoV-2-related mortality in mice.
COVID-19
SARS-CoV-2
cellular senescence
senolytics
survival
Journal
Aging cell
ISSN: 1474-9726
Titre abrégé: Aging Cell
Pays: England
ID NLM: 101130839
Informations de publication
Date de publication:
03 2023
03 2023
Historique:
revised:
07
12
2022
received:
22
04
2022
accepted:
20
12
2022
pubmed:
28
1
2023
medline:
17
3
2023
entrez:
27
1
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 36704839
doi: 10.1111/acel.13771
pmc: PMC10014049
doi:
Substances chimiques
Quercetin
9IKM0I5T1E
Dasatinib
RBZ1571X5H
Senotherapeutics
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13771Informations de copyright
© 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.
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