Corylin promotes healthy aging via RAGA-mTOR suppression and sex-dependent activation of SIRT3.
Summary
Mid-life Corylin improved metabolic and physical function and extended female mouse lifespan by 11.9%, with a 33% higher survival at 125 weeks. Multi-omics linked Corylin to RAGA-mediated mTOR suppression and restoration of SIRT3 and energy programs in females, explaining sex-dependent benefits.
Key Findings
- Corylin extended median lifespan by 11.9% in female mice with 33% higher survival at 125 weeks; no similar benefit in males.
- Integrated multi-omics linked Corylin to suppression of mTOR signaling via direct interaction with RAGA.
- Corylin restored SIRT3 protein levels and energy metabolism programs in females, aligning with sex-dependent benefits.
Clinical Implications
Suggests a candidate pathway (RAGA-mTOR and SIRT3) for geroprotective interventions and supports sex-specific trial design. Potential applications include metabolic and musculoskeletal aging and possibly dermatologic anti-aging strategies.
Why It Matters
Identifies a small molecule geroprotector with sex-specific efficacy and a defined RAGA-mTOR/SIRT3 mechanism, advancing translational aging biology. The mechanistic clarity provides targets for future clinical development.
Limitations
- Preclinical mouse study; human translatability and safety remain unknown
- Sex-specific benefit limited to females; mechanisms in males unresolved
Future Directions
Evaluate pharmacokinetics, safety, and biomarkers in humans; test dermatologic and musculoskeletal endpoints; dissect sex-specific signaling to optimize personalized geroprotection.
Study Information
- Study Type
- Basic/Mechanistic
- Research Domain
- Pathophysiology
- Evidence Level
- V - Preclinical mechanistic study in mice without human subjects
- Study Design
- OTHER