Abstract:The anti-aging effect and underlying mechanism of oleuropein were investigated in this study, where a 0.11 mol?L-1 glucose diet-induced chronic high-glucose oxidative stress model was established, and the effects of oleuropein on lifespan, lipid metabolism, and oxidative stress-related parameters in Caenorhabditis elegans (C. elegans) were evaluated.The lifespan of C. elegans was significantly prolonged in a dose-dependent manner by 23.36%, 32.51%, and 42.01% via oleuropein at 50, 100, and 200 μmol?L-1, respectively. Concomitantly, body width and area were reduced, while the frequencies of body and head swinging were increased. The attenuation of fat accumulation in C. elegans by oleuropein was confirmed through Oil Red O/Nile Red staining and decreased levels of triglyceride (TG) and free fatty acid. Furthermore, levels of reactive oxygen species, lipofuscin, and malondialdehyde were decreased by oleuropein, while the activities of superoxide dismutase (SOD) and catalase were enhanced. At 200 μmol?L-1, the mRNA expression of daf-16, lipl-4, and sod-3 was upregulated by 2.47-fold, 1.39-fold, and 2.20-fold, respectively, and the nuclear translocation ratio of DAF-16 in TJ356 C. elegans was reduced by 56.80%. In contrast, no effects on lifespan, TG content, or SOD activity were observed in CF1038 C. elegans. In conclusion, oleuropein was demonstrated to effectively have the lifespan of C. elegans extended and anti-aging effects exerted, with its mechanism being attributed to daf-16-mediated modulation of lipid metabolism homeostasis and antioxidant stress responses. A solid theoretical foundation for the translational development and practical application of oleuropein is provided by this finding.
