Daoxu Zhang, Chengyi Wu, Zhiyang Ding, Yunyu Hong, Yehan Lu, Kunpeng Zhou, Ruixue Deng, Laijia Li, Chao Li, Yi Yang, Conglong Xia, Jian Li, Wenwen Liu, Faliang An, Zelan Hu
ABSTRACT Vicatia thibetica de Boiss ( V. thibetica ) is a medicinal and edible plant traditionally used by the Bai ethnic community in Yunnan, China. Previous studies have reported that extracts derived from its roots have anti‐aging effects, although the active components remain to be further investigated. Our preliminary findings revealed that the V. thibetica crude polysaccharide (VTCP) extends the lifespan of nematodes. In the present study, we systematically investigated the anti‐aging effects of VTCP in both d ‐galactose‐induced and naturally aged mouse models with particular emphasis on the heart and kidneys as primary organs of interest. The results demonstrated that VTCP significantly reduced the expression of senescent biomarkers and alleviated fibrosis levels in both the heart and kidney. In the d ‐galactose‐induced aging model, VTCP exhibited potent antioxidant and anti‐inflammatory capacities, effectively lowering oxidative stress markers and the senescence‐associated secretory phenotypes (SASPs) in cardiorenal tissues. More importantly, in naturally aged mice, VTCP remarkably reshaped the gut microbiota composition, characterized by a significant enrichment of beneficial bacteria with the short‐chain fatty acids producing potential and a suppression of inflammation‐associated genera. Based on these findings, we propose that the core mechanism of VTCP likely involves targeted modulation of the gut microbiota to promote the production of beneficial metabolites, which subsequently suppresses systemic oxidative stress and inflammation, ultimately leading to synergistic protection of cardiorenal tissues. Collectively, our results highlight the promising potential of VTCP in counteracting cardiorenal aging and implicate the modulation of the gut‐heart/kidney axis as an underlying mechanism.