近年来的研究表明，肥胖是加速中老年人群体衰老的重要因素，但其内在机制尚有待深入研究。我们前期的研究结果显示，下丘脑神经干细胞在高脂肪饮食诱导的肥胖发生和衰老中均发挥着重要的作用，饮食诱导的肥胖能够导致下丘脑神经干细胞早衰。因此，我们推测下丘脑神经干细胞早衰是加速肥胖人群机体衰老的重要影响因素。为了研究其内在分子机制，我们拟建立饮食诱导的肥胖小鼠模型，分离下丘脑神经干细胞，利用单细胞测序技术进行测序并进行生物信息学分析，比较肥胖小鼠下丘脑神经干细胞在不同年龄阶段的细胞亚群组成变化以及各亚群中基因调控网络的改变。寻找调控神经干细胞衰老的关键因子，并开展后续的功能和机理研究。本项目的研究成果将揭示饮食诱导的肥胖导致神经干细胞早衰的内在机制，以期为机体衰老的分子机制研究提供新的理论，进而为临床早衰的预防提供重要的干预靶点。

In recent years, studies have shown that obesity is an important factor in accelerating population aging, but the internal mechanism remains elusive.Our previous studies have revealed that hypothalamic neural stem cells play an important role in the development of high-fat diet induced obesity and aging, and high fat diet induced obesity can lead to premature aging of hypothalamic neural stem cells.Therefore, we speculated that hypothalamic neural stem cells premature aging may play key roles to accelerate aging. To explore the underlying molecular mechanisms, we proposed to separate neural stem cells from the hypothalamus of diet induced obese mice. After single cell sequencing and bioinformatics analysis, we will investigatethe composition changes in each neural stem cells subpopulation at different time point of aging and analyze gene regulatory networks in each subpopulation.The roles of candidate key factors that regulate the aging of neural stem cells will be studied. The results of this project will not only reveal the internal mechanism of dietary obesity-induced premature aging of neural stem cells, but also provide a new theory for elucidating molecular mechanism of aging, and provide potential intervention targets for the prevention of clinical premature senility.