内皮祖细胞（Endothelial Progenitor Cells，EPCs）衰老在血管老化及老龄相关性疾病中具有重要作用，但关键分子机制未明。我们前期研究发现老年个体肠道菌群色氨酸代谢明显减低，可能与EPCs数量减少、功能减退相关，且芳香烃受体（AhR）作为色氨酸代谢产物主要受体广泛表达于EPCs，可能介导EPCs功能调控。此外，Nrf2抑制EPCs氧化应激参与调控血管老化，而MAPK维持EPCs干细胞特性促进血管修复。以此为切入点，本项目将通过在体色氨酸限制饮食、AhR基因敲除、AhR受体激活以及体外沉默或过表达AhR相关通路，重点探讨色氨酸AhR-Nrf2通路在调节氧化应激改善EPCs迁移、成管功能中的作用，以及AhR-MAPK途径在调节EPCs增殖分化促进衰老相关血管损伤修复中的作用，为调控血管老化提供理论基础和潜在靶点。

Endothelial progenitor cells (EPCs) plays an important role in vascular aging and aging related diseases, but the key molecular mechanism remains unclear. Our previous study found that gut microbiota-derived tryptophan metabolism in elderly individuals was significantly decreased, which may be related to the decrease of the number and function of EPCs. And aromatic hydrocarbon receptor (AhR) as the main receptor of tryptophan metabolite is widely expressed in EPCs, which may mediate the regulation of EPCs function. In addition, Nrf2 inhibited the oxidative stress of EPCs and participated in the regulation of vascular aging, while MAPK maintained the stem characteristics of EPCs and promoted vascular repair. As the starting point, the current project will focus on the role of AhR-Nrf2 pathway in regulating oxidative stress and improving the migration and tubular function of EPCs, and the role of AhR-MAPK pathway in regulating the proliferation and differentiation of EPCs and promoting the repair of aging related vascular damage, through in vivo tryptophan restriction diet, AhR gene knockout, AhR receptor activation, and in vitro silencing or overexpression of AhR related pathways. It will provide a theoretical basis and potential target for the regulation of vascular aging.