Abstract: Objective: The purpose of this study was to investigate the anti-aging effect of phloretin on Caenorhabditis elegans and the underlying mechanism. Methods: The effect of treatment with different concentrations of phloretin (25, 50 and 75 μg/mL) on the survival rate, motility, pharynx pumping ability, lipofuscin and reactive oxygen species (ROS) levels, and stress resistance (hydrogen peroxide, high temperature, and ultraviolet) of C. elegans was analysed. The mechanism of action of phloretin in prolonging the lifespan of C. elegans was explored by measuring antioxidant enzyme activities and related gene expression levels as well as using mutant C. elegans. Results: Phloretin could significantly promote the longevity of C. elegans, inhibit the decline of its motility, related to senescence, increase stress resistance, enhance free radical scavenging capacity and antioxidant enzyme activities (superoxide dismutase (SOD) and catalase (CAT)), and reduce the accumulation of lipofuscin and the content of malonaldehyde (MDA). Phloretin significantly down-regulated the mRNA expression levels of daf-2 and age-1 (P < 0.05, P < 0.01), but up-regulated the mRNA expression levels of daf-16 and sir-2.1(P < 0.05, P < 0.01). Phloretin failed to prolong the lifespan of the mutants daf-2 (e1370), daf-16 (mu86), and sir-2.1 (ok434), but significantly prolonged the lifespan of the mutant eat-2 (ad1116) (P < 0.05). In addition, phloretin promoted the nuclear localization of DAF-16, and activated the mRNA expression of its downstream target genes sod-3, ctl-1 and hsp-16.2. Conclusion: Phloretin can promote the nuclear localization of DAF-16 through the insulin signaling pathway and the SIR-2.1 signaling pathway, and improve stress resistance and antioxidant capacity, thus prolonging the lifespan of C. elegans.

Key words: Caenorhabditis elegans; phloretin; daf-16; antioxidant capacity; lifespan