老化过程中伴随着脑室管膜下区(SVZ)和海马齿状回的颗粒下层(SGZ)神经发生的明显下降，但机制不明。近年研究表明星形胶质细胞是神经发生微环境的重要成员，对神经发生的各个环节均发挥了关键的调节作用。我们的前期研究发现，老化过程中SVZ及邻近区域的星形胶质细胞出现了SA-β-Gal染色强阳性、DNA双链断裂等衰老特征。但星形胶质细胞衰老对神经干细胞的维持和神经发生的影响及机制还远未被阐明。本项目拟研究增龄过程中星形胶质细胞调节谷氨酸稳态和表达Wnt、Jagged-1及ephrin-B2等重要信号分子的变化，旨在揭示星形胶质细胞老化参与了神经发生的下降及可能的机制。在此基础上，以氧化应激诱导的衰老星形胶质细胞和神经干细胞共培养的模型，进一步探讨星形胶质细胞衰老对体外神经发生的影响及调控机制。本研究将为SVZ神经发生下降的机制提供新的认识，同时也为延缓神经干细胞的老化提供新的策略。

Neurogenesis in the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone (SGZ) of the hippocampal dentate gyrus declines with increasing age. Little is known about the mechanism that how aging affects the self-renewl of neuronal stem cell and neurogenesis. In recent years, studies have shown that astrocytes are a key component of the neurogenic niches and play important roles in regulating multiple aspects of adult neurogenesis. Our preliminary data showed that astrocyte in SVZ and adjacent to SVZ appeared the characteristics of the senescent cells including strong senescence-associated β-galactosidase （SA-β-Gal）staining and expression of γ-H2AX, which is the marker of DNA double-strand break. However, it is far from clear how senescent astrocyte regulate the neural stem cells self-renewal and neurogenesis. Therefore, this project will study the changes of astrocyte function in regulating glutamate homeostasis and expressing important signal molecules such as Wnt、Jagged-1 and ephrin-B2 with increasing age. This study will reveal the essence that senescent astrocytes decrease the neurogenesis and possible mechanism. Furthermore, using senescent astrocytes induced by oxidative stress and neuronal stem cells co-culture model, it will be further investigated that how senescent astrocytes affects the neurogenesis in vitro. Overall the proposed work will advance a new understanding of aging-related decline in neurogenesis and provide new strategies for delaying the aging of stem cells in future.