SIRT2 suppresses aging-associated cGAS activation and protects aged mice from severe COVID-19.
Total: 83.0Innovation: 9Impact: 7Rigor: 8Citation: 9
Summary
In aged hosts, SIRT2 limits cGAS activation and mitigates severe SARS-CoV-2 disease; aged SIRT2-deficient mice exhibit exacerbated COVID-19, highlighting a mechanistic link between aging, innate DNA sensing, and outcomes.
Key Findings
- Aged SIRT2-deficient mice develop more severe disease following SARS-CoV-2 infection.
- SIRT2 suppresses aging-associated cGAS activation, linking sirtuin biology to innate antiviral responses.
- Data support SIRT2 as a protective factor in severe COVID-19 pathogenesis in aged hosts.
Clinical Implications
Supports exploration of SIRT2 activation or cGAS–STING modulation as therapeutic strategies in elderly COVID-19, pending translational validation.
Why It Matters
Identifies a tractable pathway (SIRT2–cGAS) that may be targeted to reduce severe COVID-19 in older adults.
Limitations
- Preclinical animal data; human translational relevance needs confirmation
- Abstract details are limited in the provided text; specific effect sizes are not reported here
Future Directions
Test pharmacologic SIRT2 activation or cGAS modulation in aged animal models and early-phase clinical studies; map cell-type specificity and safety profile.
Study Information
- Study Type
- Basic/Mechanistic research
- Research Domain
- Pathophysiology
- Evidence Level
- V - Preclinical mechanistic study in aged mice with viral challenge
- Study Design
- OTHER