Corylin promotes longevity in Caenorhabditis elegans through DAF-16 and SKN-1 coordinated activation of autophagy-mitochondrial homeostasis axis.

<h4>Ethnopharmacological relevance</h4>Corylin is a natural flavonoid isolated from the seeds of Psoralea corylifolia L., a traditional medicinal herb historically used to treat bone-related disorders such as osteoporosis. However, its role in organismal aging and the underlying molecular mechanisms remain largely unexplored.<h4>Aim of the study</h4>This study aimed to evaluate the anti-aging efficacy of corylin and elucidate the molecular basis of its action.<h4>Materials and methods</h4>Using Caenorhabditis elegans (C. elegans) as a model organism, we systematically assessed the impact of corylin on lifespan and multiple aging-associated phenotypes, including locomotor capacity, muscle integrity, lipofuscin accumulation, and resistance to thermal, pathogenic, and oxidative stress. Neuroprotective potential was evaluated using transgenic models of Parkinson's and Huntington's diseases. To uncover the mechanisms involved, we analyzed the DAF-16/SKN-1 signaling axis and autophagy(definition)-related processes using transgenic reporter strains, RNA interference, and RT-qPCR.<h4>Results</h4>Corylin treatment significantly extended lifespan, improved locomotor performance, and reduced lipofuscin accumulation. Furthermore, it enhanced resistance to environmental stresses and conferred neuroprotection in models of neurodegeneration. Mechanistically, corylin promoted nuclear translocation of DAF-16 and upregulated the expression of DAF-16/SKN-1 target genes. This transcriptional activation was associated with enhanced autophagic flux and improved mitochondrial quality. Crucially, the beneficial effects of corylin were abolished in daf-16 and skn-1 mutants, as well as under autophagy-deficient conditions.<h4>Conclusion</h4>Corylin exerts multifaceted anti-aging effects in C. elegans by coordinately activating the DAF-16/SKN-1 signaling axis, thereby enhancing autophagic flux and maintaining mitochondrial homeostasis. These findings identify corylin as a promising natural candidate for aging intervention.