Tricin Delays Aging and Enhances Muscle Function via Activating AMPK-Mediated Autophagy in Diverse Model Organisms

Aging leads to progressive decline in the functions of cells, tissues, and organs, severely affecting muscle performance and overall health, highlighting the urgent need for effective therapeutic agents. This study investigated the antiaging properties of tricin, a flavonoid abundant in grains, using biological models, including human fibroblasts, <i>Caenorhabditis elegans</i> (<i>C. elegans</i>), and mice. Tricin significantly alleviated the senescent phenotype in human fibroblasts induced by D-galactose (D-gal), doxorubicin, and replicative senescence, as evidenced by reduced SA-β-gal activity, downregulated senescence markers (p16, p21), and decreased SASP factors. Mechanistically, tricin binds to AMPK and activates the AMPK-mTOR-p70S6K signaling pathway, promoting autophagy and delaying cellular aging. In vivo, tricin extended lifespan, enhanced stress resistance, and improved mobility in <i>C. elegans</i> through <i>aak-2</i>/<i>AMPK</i>-mediated autophagy. In D-gal-induced aging mice, tricin improved muscle function, reducing p16, p21, and SASP expression in muscle tissues. These findings underscore tricin's potential as a promising antiaging therapeutic via AMPK-mediated autophagy activation.