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.
Longevity & Aging