Unveiling the Anti-aging Activities and Mechanism of Melibiose: Insights from Metabolomics and RT-qPCR Analyses.

Abstract

In this study, the anti-aging potential of melibiose was examined, and its molecular mechanism was elucidated using Caenorhabditis elegans as a model organism. The findings demonstrated that melibiose at concentrations of 100 μM, 150 μM, and 200 μM significantly increased nematode lifespan by 15.38%, 23.08%, and 30.77% respectively. Additionally, melibiose enhanced resistance against heat and oxidative stress, improved nematode motility, reduced lipofuscin and reactive oxygen species (ROS) accumulation, and increased antioxidant enzyme activity. Through the use of gene-deletion nematodes, transgenic nematodes, RT-qPCR, and metabolomics, it was determined that melibiose potentially exerts its effects through multiple pathways including the insulin signaling pathway (down-regulation of daf-2 and age-1, up-regulation of sod-3 and hsp-16.2), the AMP-activated protein kinase (AMPK) pathway (up-regulation of aak-2), and the JNK pathway (up-regulation of jnk-1). Activation of transcription factors DAF-16, SKN-1, and HSF-1 was observed, moreover, delaying the aging process by promoting autophagy (upregulation of lgg-1 and bec-1) and mitochondrial function (upregulation of hsp-6, hsp-60, and mev-1) to resist oxidative damage. And its anti-aging signature metabolites may be Carbimazole, 4-Hydroxy-2-oxoglutaric acid, and 1,4-Dithiothreitol.