Senolytics reduce coronavirus-related mortality in old mice

Area of Science:

• Immunology
• Gerontology
• Virology

Background:

• Cellular senescence is linked to inflammation and chronic diseases, but its role in viral infection response remains unclear.
• The elderly and chronically ill show high vulnerability to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Purpose of the Study:

• To investigate the impact of cellular senescence on viral infection, specifically SARS-CoV-2.
• To evaluate the efficacy of senolytic drugs in mitigating viral infection severity and mortality.

Main Methods:

• Senescent cells (SnCs) were analyzed for inflammatory responses to pathogen-associated molecular patterns (PAMPs), including SARS-CoV-2 spike protein.
• Old mice infected with a SARS-CoV-2-related coronavirus were treated with senolytic drugs.
• Mortality, senescence markers, inflammation, and antiviral antibody levels were assessed.

Main Results:

• Senescent cells exhibited hyper-inflammatory responses to PAMPs, upregulating viral entry proteins and downregulating antiviral genes in neighboring cells.
• Infected old mice showed high mortality, increased senescence, and inflammation.
• Senolytic treatment significantly reduced mortality, senescence, and inflammation, while boosting antiviral antibodies.

Conclusions:

• Cellular senescence exacerbates viral infections through a pro-inflammatory paracrine mechanism.
• Reducing the senescent cell burden may enhance resilience and decrease mortality in aged or diseased individuals facing viral threats like SARS-CoV-2.