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Enhancing Quercetin Bioavailability Attenuates Aging Phenotypes via the Gut Microbiota–Intestinal Barrier Axis in Aged Mice

Naito Y, Mizushima K, Inoue R, Takagi T

2026

Abstract

Aging is characterized by a progressive decline in physiological functions driven by cellular senescence, chronic inflammation, and alterations in the gut microbiota. Quercetin is a potential anti-aging compound; however, its clinical application is limited by low bioavailability. In this study, we investigated whether enhancing quercetin bioavailability using EubioQuercetin (EQN) improves aging phenotypes by modulating the gut microbiota–intestinal axis. Male C57BL/6J mice were treated with EQN or conventional quercetin for 12 weeks. Aging phenotypes were assessed using a composite aging score based on hair glossiness, hair loss, and the presence of white hair. Gut microbiota composition was analyzed via 16S rRNA sequencing with centered log-ratio transformation, and intestinal gene expression was evaluated via quantitative reverse transcription-polymerase chain reaction. Notably, EQN significantly reduced the aging score compared to the control (median = 4.5 vs. 8; p < 0.01), with greater efficacy than conventional quercetin. Microbiota analysis identified taxa that were positively (Lactobacillus, Romboutsia, Desulfovibrio, and Lachnoclostridium) and negatively (Akkermansia and Christensenellaceae) associated with aging. EQN selectively suppressed aging-associated taxa and increased the abundance of beneficial bacteria. It also downregulated the expression levels of senescence-related genes (p21, proliferating cell nuclear antigen, and leucine-rich repeat-containing G…

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Evidence Hub reads this as a preprint, done in animal, not in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.

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