Role of Antioxidative Peptide Gly-Met Derived From Goat Milk Dadih Toward Antiaging Effects Through the SKN-1/Nrf2 Pathway in C. elegans

Abstract

Fermented dairy products have been studied for their physiological functions, particularly their antioxidant properties. Dadih is a traditional Indonesian fermented dairy product produced from buffalo milk and prepared in bamboo tubes that exhibit functional properties. Compared to cow milk, goat milk has gained more attention for dadih production due to its low allergen count and ease of digestion. In our previous study, we identified the dipeptide glycine-methionine (Gly-Met) generated from goat milk dadih as a novel antioxidant peptide. This study aimed to investigate the antiaging effects of Gly-Met in Caenorhabditis elegans using an in vivo model. Initially, the effective concentration (EC₅₀) was determined and Gly-Met exhibited an effective antioxidant activity value of 0.96 mg/mL. Our results demonstrated that Gly-Met significantly extended the mean lifespan, enhanced resistance to oxidative stress, and reduced reactive oxygen species (ROS) accumulation in C. elegans. Furthermore, the mRNA expression of Nsy-1, Sek-1, and Pmk-1 that are the target genes of the p38 MAPK signaling pathway was upregulated in C. elegans. Subsequently, Skn-1 and Gcs-1 expression levels were significantly upregulated. Activation of SKN-1 target genes may be modulated by the p38 MAPK signaling pathway. Our study revealed that Gly-Met, an antioxidative peptide identified in goat milk dadih, may contribute to antiaging effects through the SKN-1/Nrf2 signaling pathway in C. elegans.