内皮祖细胞（EPC）衰老可导致其生物学功能减退及血管修复能力降低，进而参与动脉粥样硬化发生发展，是亟待解决的科学问题。Klotho是关键的抗衰老物质，可抑制EPC衰老，但机制远未清晰。我们发现在klotho基因敲除的早衰小鼠，EPC衰老、线粒体自噬活性减弱（线粒体与自噬体共定位减少）；而klotho干预则可激活线粒体自噬，提示线粒体自噬可能是klotho抑制EPC衰老的新途径。因此，我们拟以klotho基因敲除小鼠为衰老模型，进一步评价klotho调控线粒体自噬对EPC衰老及生物学功能的影响；其次探讨Klotho是否通过IGF-1/FOXO信号通路调控线粒体外膜蛋白受体BNIP3，介导线粒体自噬；最后观察klotho调控线粒体自噬在EPC修复损伤血管中的作用。本课题首次发现并提出线粒体自噬调控EPC衰老的新观点，是对既往研究的进一步深化，有望揭示血管损伤修复新机制，具有重要的研究价值。

Senescent endothelial progenitor cell（EPC）featured with decreased biological function and impaired vessel repair may lead to atherosclerosis, especially in aging population. Klotho, a key anti-aging protein, can inhibit EPC senescent, but the mechanism is not clear. We found senescent EPC with partly impaired mitophagy in klotho gene knock-out accelerated aging mice. Furthermore, klotho treatments can active mitophagy in EPC. All these findings indicate mitophagy is the target of klotho-modulated EPC improvement. Therefore, we plan to fully evaluate the effect of klotho on senescent EPC mitophagy and biological function in kloth-/- mice; to clarify if klotho actives BNIP3 and mitophagy via IGF/FOXO; to evaluate the effect and mechanism of klotho on vessel repair with senescent EPC. We for the first time report a novel mechanism of klotho-mediated EPC senescent inhibition which is very important for atherosclerosis study.