星形胶质细胞是神经系统中数量最多的细胞，参与了大脑的发育、成熟、衰老和神经系统退行病变等多个过程。既往研究表明，Ogt介导的O-GlcNAc修饰是重要的蛋白翻译后修饰过程，在神经系统功能调控、神经系统疾病的发生和发展中发挥重要作用。但是关于星形胶质细胞中Ogt介导的O-GlcNAc修饰在脑衰老、脑衰老向神经退行演变过程中的功能目前国际上未见报道。本研究聚焦于脑衰老和神经退行演变这一关键科学问题，采用多种实验方法和模型，通过在体外和体内特异性操控星形胶质细胞Ogt，揭示衰老过程中Ogt对星形胶质细胞基因表达和功能调控、小鼠认知功能的影响，阐明星形胶质细胞中Ogt和O-GlcNAc修饰在脑衰老向神经退行演变的作用和分子机制，为干预脑衰老和预防神经退行演变提供新的思路和靶点。

As the most abundant cells in the nervous system, astrocytes play essential roles in the development, maturation, ageing and neurodegeneration of brain, etc. Previous studies have shown that Ogt-mediated O-GlcNAc modification, an important post-translational modification, regulates the neuronal function and involves in the neurological disorders. However, it remains largely unknown regarding the function of astrocytes Ogt and O-GlcNAc modification in the process of brain ageing, and the development from ageing to neurodegeneration. Targeting on this key question, our study will utilize multiple experimental technologies and models, and modulate astrocytes Ogt in vitro and in vivo. Our study will reveal the effects of Ogt on gene expression and function of astrocytes, and cognitive function of mice. Further, our study will determine the reoles of mechanism of astrocytes Ogt and O-GlcNAc modification in brain ageing and its shift to neurodegeneration. Our findings will provide novel idea and targets for intervening the brain ageing and neurodegeneration.