Abstract
2-O-β-D-Glucopyranosyl ascorbic acid (AA-2βG), a bioactive ascorbic acid derivative isolated from the fruits of Lycium barbarum L., exhibited significant antiaging effects in Caenorhabditis elegans. It significantly extended their lifespan, enhanced stress resistance, reduced lipofuscin accumulation, and improved their healthspan, while strengthening antioxidant defenses. Transcriptomic analysis identified the insulin/insulin-like growth factor (IGF)-1 signaling pathway as a key regulator, with quantitative real-time polymerase chain reaction confirming the upregulation of longevity-associated genes. Functional studies showed that the transcription factors DAF-16, HSF-1, and SIR-2.1 were essential for the lifespan-extending effects of AA-2βG, as mutations in these genes abolished lifespan extension. Moreover, 16S rRNA sequencing revealed that AA-2βG modulated gut microbiota by increasing longevity-associated taxa and reducing pro-aging species, with these alterations linked to metabolic pathways. These findings suggest that AA-2βG exerts antiaging effects through the coordinated regulation of the IIS pathway and gut microbiota composition, highlighting its potential as a natural geroprotective compound.