Jujuboside A extends healthspan and enhances resistance of oxidative stress in Caenorhabditis elegans via the transcription factor DAF-16/FOXO3A and SKN-1/Nrf2

Jujuboside A (JA) is a biologically active saponin primarily extracted from sour jujube seeds. Existing studies have demonstrated that JA plays significant roles in anti-inflammatory, antioxidant, neuroprotective, and metabolic regulation. However, its mechanisms in lifespan extension and antioxidation remain to be further elucidated. In this study, we found that JA extended the lifespan of Caenorhabditis elegans in dose-dependent manner. JA increased the locomotion and decreased the aging pigment but did not affect the reproductive performance in C. elegans . Furthermore, by screening the signaling pathway, we showed that JA extends the healthspan in a manner dependent on the transcription factors DAF-16/FOXO3A and SKN-1/Nrf2. In addition, we found that JA enhanced the mRNA levels of DAF-16 target genes, such as sod-3 , hsp-12.6 , dod-3 , lys-7 , and thn-2 and SKN-1 target genes, such as gst-4 , gst-10 , and gcs-1 . Meanwhile, JA increased the expression of sod-3::GFP and gst-4::GFP . Moreover, we found that JA also enhanced oxidative stress resistance in a manner dependent on the transcription factors DAF-16/FOXO3A and SKN-1/Nrf2. In summary, our study demonstrates that JA extends healthspan and enhances the resistance of oxidative stress in C. elegans via transcription factor DAF-16/FOXO3A and SKN-1/Nrf2.