White Tea Aqueous Extract: A Potential Anti-Aging Agent Against High-Fat Diet-Induced Senescence in Drosophila melanogaster

White tea has been scientifically proven to exhibit positive biological effects in combating chronic diseases, including cancer, metabolic syndrome, etc. Nevertheless, the anti-aging activity and mechanism of white tea on organisms exposed to a high-fat diet remain unexplored. Herein, we prepared a white tea aqueous extract (WTAE) from white peony in Fuding and assessed its in vivo antioxidant and anti-aging effects by employing a <i>Drosophila melanogaster</i> senescence model induced by lard, delving into the underlying molecular mechanisms through which the WTAE contributes to lifespan improvement. Notably, the WTAE significantly extended the lifespan of <i>Drosophila</i> fed a high-fat diet and partially restored the climbing ability of <i>Drosophila</i> on a high-fat diet, accompanied by increased activities of copper-zinc superoxide dismutase, manganese-superoxide dismutase, and catalase and decreased lipid hydroperoxide levels in <i>Drosophila</i>. Furthermore, transcriptomic analysis indicated that the WTAE countered aging triggered by a high-fat diet via activating oxidative phosphorylation, neuroactive ligand-receptor interactions, and more pathways, as well as inhibiting circadian rhythm-fly, protein processing in the endoplasmic reticulum, and more pathways. Our findings suggest that WTAE exhibits excellent inhibitory activity against high-fat diet-induced senescence and holds promising potential as an anti-aging agent that can be further developed.