Removal of senescent cells reduces the viral load and attenuates pulmonary and systemic inflammation in SARS-CoV-2-infected, aged hamsters.
Journal
Nature aging
ISSN: 2662-8465
Titre abrégé: Nat Aging
Pays: United States
ID NLM: 101773306
Informations de publication
Date de publication:
07 2023
07 2023
Historique:
received:
09
08
2022
accepted:
24
05
2023
medline:
21
7
2023
pubmed:
7
7
2023
entrez:
6
7
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 37414987
doi: 10.1038/s43587-023-00442-w
pii: 10.1038/s43587-023-00442-w
pmc: PMC10353934
doi:
Substances chimiques
navitoclax
XKJ5VVK2WD
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
829-845Informations de copyright
© 2023. The Author(s).
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