Gastrodin extends the lifespan of Caenorhabditis elegans via the DAF-16/FOXO signaling pathway and autophagy

Abstract Objective The progression of age-related pathologies is strongly linked to biological aging. Identifying natural anti-aging agents to mitigate disease onset and development holds substantial therapeutic value.The natural compound Gastrodin (Gas) demonstrates promising effects in retarding aging.This study aims to explore the effects of Gas on the lifespan and antioxidant capacity of Caenorhabditis elegans (C. elegans). Additionally, it seeks to elucidate the possible mechanisms. Methods Initially, Gas was assessed for its influence on C. elegans lifespan, mobility, lipofuscin accumulation, and oxidative stress responses. Subsequent analyses focused on Gas’s modulation of the insulin/IGF-1 pathway, mitochondrial activity, autophagic processes, and gene expression to uncover its lifespan-extending mechanisms. Results Gas induced a dose-dependent lifespan extension in C. elegans, peaking at 400 µM with a 17.3% increase in longevity. Gas enhanced C. elegans mobility while suppressing age-related lipofuscin deposition.Additionally, Gas lowered ROS levels and elevated antioxidant enzyme activity in C. elegans.Mechanistic studies revealed that Gas’s anti-aging effects rely on transcription factors (DAF-16, SKN-1, HSF-1) and bolster stress resistance via HSPs activation and autophagy induction. Conclusion This study reveals the potential of Gas in extending the lifespan of C. elegans, emphasizes its mechanism of action by regulating antioxidant capacity, heat stress response, and autophagy pathway, and provides experimental evidence that supports the development of Gas as a candidate compound for lifespan extension.