Dihydromyricetin alleviates immunosenescence by modulating the conserved TAK1/MAP3K7 axis

Aging is characterized by a progressive decline in physiological integrity, with immunosenescence and chronic inflammation (often termed inflammaging) playing critical roles. This persistent low-grade inflammation and immune dysfunction contribute significantly to age-related pathologies. While natural compounds like Dihydromyricetin (DHM) show promise in anti-aging, their precise upstream immunomodulatory targets and cross-species mechanisms have remained largely uncharacterized. Understanding these specific pathways is crucial for developing targeted interventions to combat age-related immune dysregulation.

Researchers investigated Dihydromyricetin's (DHM) immunomodulatory effects using a combination of transcriptomic analyses and cross-species assays. They utilized a Drosophila model to assess DHM's impact on basal antimicrobial peptide expression and acute pathogen clearance. Additionally, a mammalian H₂O₂-induced stress-induced premature senescence (SIPS) model was employed to evaluate DHM's ability to suppress the senescence-associated secretory phenotype (SASP). Crucially, genetic silencing techniques were applied to identify the immune-regulatory kinase TAK1 (and its mammalian homolog MAP3K7) as a potential mediator of DHM's benefits.

Dihydromyricetin (DHM) systematically downregulated basal antimicrobial peptide expression in Drosophila, effectively resolving chronic inflammaging while maintaining robust acute pathogen clearance. In the mammalian H₂O₂-induced SIPS model, DHM significantly suppressed the senescence-associated secretory phenotype (SASP). Genetic silencing experiments revealed that the immune-regulatory kinase TAK1 was fundamentally required for the lifespan-extending benefits of DHM observed in Drosophila.