Corylin, a flavonoid from Psoralea corylifolia, extended median lifespan by 11.9% in female mice when administered during mid-life, with 33% higher survival rates at 125 weeks. The compound directly interacts with RAGA protein to suppress mTOR signaling—a key longevity pathway—while restoring SIRT3 levels and energy metabolism specifically in females. This sex-dependent response represents a fascinating dimension in longevity research, suggesting hormonal or genetic factors may influence how anti-aging compounds work. The mTOR suppression mechanism aligns with established longevity interventions like rapamycin and caloric restriction, positioning Corylin as a potential natural alternative. However, the complete absence of male benefits raises critical questions about translation to humans, where sex differences in aging are more nuanced. The mid-life timing of administration is particularly relevant for human application, as this mirrors when most adults would realistically begin anti-aging interventions. While promising, the dramatic sex specificity and single-species testing limit immediate clinical relevance. This work advances our understanding of how natural compounds might selectively target aging mechanisms, but broader species validation and mechanistic clarity around sex differences remain essential.