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

Jun 9, 2026Nature communications

Corylin supports healthy aging by reducing a growth pathway and activating a cell energy regulator differently in males and females

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Longevity & Aging on OpenScience ↗PubMed ↗DOI ↗OA ↗

Abstract

Corylin administration in mid-life leads to an 11.9% increase in median lifespan for female mice.

Corylin improves metabolic function, muscle integrity, and physical performance in mice on a standard diet.
An increased survival rate of 33% at 125 weeks is observed in female mice treated with Corylin.
No comparable lifespan extension is noted in male mice receiving the same treatment.
Multi-omics analyses indicate that Corylin modulates age-associated molecular changes across multiple tissues.
Corylin treatment is linked to the suppression of specific cellular signaling pathways and restoration of certain protein levels.

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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.