我国面临人口老龄化的严峻挑战，肾脏衰老及功能减退是导致老年人肾脏病的生物学基础，研究肾脏衰老机制减少老年肾脏疾病发生，是实现健康老龄化的重大需求。我们前期构建了青年-老年大鼠肾脏交互移植模型，发现机体内环境可影响肾脏衰老，且Sod1是参与肾脏衰老的重要蛋白。我们以竞争性内源性RNA（ceRNA）为切入点发现lncRNA ZFAS1与miR-302e及Sod1可构成ceRNA调控网络参与肾脏衰老，我们进一步将研究窗口前移，发现甲基化识别蛋白YTHDF2可通过m6A修饰影响lncRNA ZFAS1。基于此，本项目将以研究甲基化识别蛋白YTHDF2通过影响Sod1相关ceRNA参与肾脏衰老的具体机制为目标，着重阐明lncRNA ZFAS1-Sod1的ceRNA网络在肾脏衰老中的体内/外功能及关键机制，探索m6A修饰对肾脏衰老关键环节的影响，为延缓肾脏衰老、老年肾脏病的防治提供干预靶点和理论依据。

China is faced with the severe challenge of population aging, renal aging and dysfunction are the biological basis of kidney disease in the elderly. Thus, studying the mechanism of renal aging to reduce the occurrence of kidney disease in the elderly is a major demand for healthy aging. In the preliminary work, we have established a young–old rat kidney transplantation model, and found that the internal environment of the body could affect renal aging, and Sod1 is an important protein involved in the renal aging. Taking competitive endogenous RNA (ceRNA) as the entry point, we found that lncRNA ZFAS1, miR-302e and Sod1 could form a ceRNA regulatory network and participate in the process of renal aging. We further moved the research window forward and found that methylated recognition protein YYTHDF2 could affect lncRNA ZFAS1 through m6A modification. Based on this, this project is to study the specific mechanism of the methylation recognition protein YTHDF2 involved in renal aging by affecting the Sod1-related ceRNA as the goal, clarify the vivo/vitro function and mechanism of lncRNA ZFAS1-Sod1 ceRNA network in renal aging, and explore the effect of m6A modification on renal aging, aiming to provide the intervention targets and theoretical basis for delaying renal aging and senile kidney disease prevention.