Neomangiferin prolongs the lifespan of Caenorhabditis elegans by regulating autophagy-dependent IIS and MAPK pathways via bas-1

Abstract

Neomangiferin (NG) is an active ingredient extracted from mango, recognized for its antioxidant potential. However, its anti-aging efficacy remains largely unexplored. This study employed Caenorhabditis elegans (C. elegans) to evaluate the anti-aging activity of NG and investigate the corresponding molecular mechanism. Our findings demonstrated that NG significantly extended the average lifespan of C. elegans, by reducing the levels of lipofuscin and reactive oxygen species (ROS), as well as improving the survival rate under heat stress, oxidative stress, and UV stress. Transcriptomics results identified bas-1—a pivotal gene governing dopamine biosynthesis—as the most significantly upregulated target, with KEGG pathway enrichment highlighting coordinated activation of autophagy systems, insulin/insulin-like growth factor signaling (IIS) pathways, and mitogen-activated protein kinase (MAPK) cascades. Subsequent qPCR and other experiments verify that NG significantly upregulates bas-1, IIS pathways (daf-16, sod-3, and ctl-1), MAPK pathways (sek-1, pmk-1, skn-1, gcs-1, and gst-4), and autophagy pathways (lgg-1 and sqst-1), and significantly increases the number of lgg-1::GFP puncta. Mechanistically, fluorescence localization assays confirmed that NG promotes nuclear translocation of daf-16 and skn-1, while genetic ablation of these transcription factors inhibited NG-mediated ROS reduction, stress resilience and lipofuscin levels. Moreover, the molecular docking results showed that NG binds to bas-1 through hydrogen bonding interactions, hydrophobic interactions and salt bridge interactions. Critically, the bas-1 mutant exhibited substantially attenuated activation of autophagy as well as the IIS and MAPK pathways, ultimately weakening NG-mediated autophagy and anti-aging efficacy. Therefore, the targeted upregulation of bas-1 by NG through activating autophagy may potentially represent a novel and promising approach for alleviating aging.