Transcriptome Analysis Reveals Norathyriol Prolongs the Lifespan via Regulating Metabolism in C. elegans

Aging and age-related diseases are closely linked to an imbalance in energy supply and demand, a condition that can potentially be mitigated through various interventions, including the use of naturally occurring molecules. Norathyriol (NL), a tetrahydroxyxanthone compound, is prevalent in mango fruit and medicinal plants. While studies have indicated that NL may influence metabolism, its effects on aging have not been extensively explored.

We conducted lifespan analysis and measured lipofuscin accumulation in C. elegans model to evaluate the effects of NL on aging. Additionally, we identified differentially expressed genes (DEGs) through comprehensive RNA-sequencing (RNA-seq) analysis and performed gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGGs) pathway analyses to elucidate the molecular mechanisms underlying NL's effects.

Our study demonstrated that NL at 50 μM extends the lifespan by 15.9% and reduces lipofuscin accumulation in C. elegans without impacting their feeding capabilities. A total of 928 DEGs were identified in NL-treated worms. The analysis of DEGs indicated that NL's longevity-promoting effects might be due to its regulation of gene expression in lipid metabolism and immune response pathways. Furthermore, the insulin/insulin-like growth factor (IGF)-1 and target of rapamycin (TOR) signaling pathways were implicated in the lifespan-extending effect of NL.

These findings broaden the bioactivity profile of polyphenols and highlight the need for further investigation into the therapeutic potential of NL in combating age-related diseases.