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

  • Shu-Fang Cheng,
  • Yu-Tsun Lin,
  • Tong-Hong Wang,
  • Yann-Lii Leu,
  • Kuo-Chiang Hsia,
  • Wen-Chih Lee,
  • Chun-Hao Feng,
  • Chen-Hsin Kuo,
  • Sien-Hung Yang,
  • Meng-Chun Wang,
  • Chieh-Yu Liu,
  • Pei-Chih Hu,
  • Yi-Cheng Hsieh,
  • Chih-Wei Yang,
  • Shu-Huei Wang,
  • Jau-Song Yu,
  • Chi-Yuan Chen,
  • Chin-Chuan Chen

摘要

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.