Senolytics reduce coronavirus-related mortality in old mice.
Science
; 373(6552)2021 07 16.
Article
in English
| MEDLINE | ID: covidwho-1262378
ABSTRACT
The COVID-19 pandemic has revealed the pronounced vulnerability of the elderly and chronically ill to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced morbidity and mortality. Cellular senescence contributes to inflammation, multiple chronic diseases, and age-related dysfunction, but effects on responses to viral infection are unclear. Here, we demonstrate that senescent cells (SnCs) become hyper-inflammatory in response to pathogen-associated molecular patterns (PAMPs), including SARS-CoV-2 spike protein-1, increasing expression of viral entry proteins and reducing antiviral gene expression in non-SnCs through a paracrine mechanism. Old mice acutely infected with pathogens that included a SARS-CoV-2-related mouse ß-coronavirus experienced increased senescence and inflammation, with nearly 100% mortality. Targeting SnCs by using senolytic drugs before or after pathogen exposure significantly reduced mortality, cellular senescence, and inflammatory markers and increased antiviral antibodies. Thus, reducing the SnC burden in diseased or aged individuals should enhance resilience and reduce mortality after viral infection, including that of SARS-CoV-2.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Aging
/
Cellular Senescence
/
Coronavirus Infections
/
Flavonols
/
Spike Glycoprotein, Coronavirus
/
Pathogen-Associated Molecular Pattern Molecules
Type of study:
Experimental Studies
/
Prognostic study
Limits:
Animals
/
Female
/
Humans
/
Male
Language:
English
Year:
2021
Document Type:
Article
Affiliation country:
Science.abe4832
Similar
MEDLINE
...
LILACS
LIS