Ginsenoside Rg1, the main active component of Panax ginseng, has been shown to improve mitochondrial function and delay cell aging by regulating chaperone-mediated mitophagy. However, how Rg1 works in Caenorhabditis elegans is still unclear. In this study, C. elegans was used as a model to study how Rg1 regulates autophagy and mitochondrial function, and to understand its anti-aging mechanism. The results showed that Rg1 treatment significantly kept cells alive and maintained muscle shape in aged C. elegans, and effectively extended their lifespan. Further studies found that Rg1 improved mitochondrial function by activating mitophagy, which helped the C. elegans better resist oxidative stress. In addition, by combining RNA sequencing and bioinformatics analysis, the transcription factor daf-16 was identified as a key target of Rg1. Experiments using daf-16 knockout strains confirmed that Rg1 produced its anti-aging effects through the daf-16 pathway, in which the activation of mitophagy and the improvement of antioxidant ability were both mediated by daf-16. In conclusion, this study shows that Rg1 slows aging in C. elegans through a daf-16-mediated mitophagy pathway, providing experimental support for the study and use of natural products in anti-aging research.
