老年急性肾损伤进展至慢性肾脏病（AKI to CKD）是尿毒症重要病因。目前研究证实，肾脏衰老是老年AKI to CKD重要机制；细胞代谢重编程（EMR）促进细胞衰老和上皮细胞间充质转化（EMT），影响肾小管上皮细胞再生修复。前期工作原创性发现年轻化内环境改善肾脏衰老、老年AKI及老年肾间质纤维化，建立了研究肾小管上皮细胞EMR、命运转变的多组学技术平台。本项目创建连体动物叠加双肾缺血再灌注损伤模型，采用单细胞测序、代谢组学、细胞因子芯片及Seahorse XF代谢分析等技术，阐明内环境调节EMR，调控肾小管上皮细胞命运转变（衰老、去分化增殖及EMT），抑制肾间质纤维化，阻抑AKI to CKD机制；筛选验证影响内环境调节肾小管上皮细胞EMR的关键因子和信号通路。丰富和发展肾脏衰老和老年AKI to CKD理论内涵，为寻找生物学标志和干预新靶点提供基础研究证据，具有重要科学价值和临床意义。

Acute kidney injury to chronic kidney disease (AKI to CKD) is an important cause of uremia in the elderly. Current studies have confirmed that kidney aging is an important mechanism of AKI to CKD. Cell energy metabolic reprogramming (EMR) promotes cell aging and epithelial cell mesenchymal transition (EMT), and affects the regeneration and repair of renal tubular epithelial cells. Our previous original study found that rejuvenation of the internal environment can improve kidney aging, AKI and renal interstitial fibrosis in the elderly. We also established a multi-omics technology platform to study EMR and fate transition of renal tubular epithelial cells. In this project, the renal ischemia-reperfusion injury model was established on the parabiotic model. Single-cell sequencing, metabolomics, cytokine chip and Seahorse XF metabolic analysis were used to clarify the mechanism of internal environment regulates EMR, regulates the fate transition of renal tubular epithelial cells (aging, dedifferentiation, proliferation and EMT), inhibit renal interstitial fibrosis, and inhibit AKI to CKD. To screen and verify the key factors and signal pathways that affect the internal environment to regulate the EMR of renal tubular epithelial cells. To enrich and develop the theoretical of AKI to CKD in kidney aging, and provide basic research evidence for screening biomarkers and new intervention targets. Therefore, this project has important scientific value and clinical significance.