Abstract: Objective: To investigate the mechanism of anti-aging effect of ethanolic extract of mulberry fruit powder on the animal model of Caenorhabditis elegans (C. elegans, nematode). Methods: To study the changes in longevity, resistance to heat stress, motility, swallowing ability and reproductive ability of nematodes after stimulation with mulberry ethanol extract (MEE). And SOD activity, CAT activity and transcript levels of anti-aging genes in nematode bodies were also investigated. Results: When the nematodes were stimulated with 5 mg/mL of MEE, the maximum lifespan extremely significantly increased by 22.24% compared to the control group (P<0.01), significantly improved the nematode motility and resistance to heat stress (P<0.05), and did not affect the reproductive capacity of the nematodes (P>0.05) when the swallowing capacity was improved by 30.43% compared to the control group. Meanwhile, the results showed that the enzymatic activity of SOD and CAT enzymes in nematodes increased by 21.44 and 13.84 U/mg prot, respectively, reducing the threshold of oxidative stress response. After treatment with 5 mg/mL of MEE, the expression levels of antioxidant genes sir-2.1 and skn-1 were up-regulated by 45.70% and 51.73%, respectively, and the expression levels of insulin genes daf-16 were up-regulated by 161.63% and daf-2 were down-regulated by 57.10%. The expression levels of hsp-16.2 and hsf-1, key regulators of life span and resistance to stress and thermal shock, were up-regulated by 121.13% and 41.07%. Conclusion: The ethanolic extract of mulberry fruit powder achieved anti-aging effects by enhancing the activity of SOD and CAT in nematodes and up-regulating the expression levels of various groups of genes in vivo.