Corylin promotes healthy aging via RAGA-mTOR suppression and sex-dependent activation of SIRT3.

Aging is accompanied by progressive physiological decline and an increased risk of chronic disease, motivating the search for interventions that promote healthy longevity. We found that mid-life administration of Corylin, a flavonoid derived from Psoralea corylifolia, improves metabolic function, muscle integrity, and physical performance in mice maintained on a standard diet. Corylin significantly extends median lifespan in female mice, with an 11.9% increase and a 33% higher survival rate at 125 weeks, whereas no comparable benefit is observed in males. Here, we show that integrated multi-omics analyses across multiple tissues reveal coordinated age-associated molecular changes modulated by Corylin. These analyses link Corylin treatment to suppression of mechanistic target of rapamycin signaling, which is further supported by direct interaction between Corylin and Ras-related GTP-binding protein A. In addition, Corylin restores sirtuin 3 protein levels and energy-associated metabolic programs in female mice, providing mechanistic insight into sex-dependent longevity benefits.