神经系统退行性变化会引发多种衰老症状或疾病的发生，但目前介导神经退行性变化的致病因子和调控机制尚不明确。衰老血液会促进器官衰老和退行性变化，但具体何种因子发挥作用并不清楚。外泌体是细胞分泌的膜结构囊泡，广泛分布于血液等循环系统，其运输的miRNA调控细胞间通讯交流，参与各项生命活动。前期研究中，我们将衰老小鼠血液外泌体注射进年轻小鼠体内后导致年轻小鼠的学习和记忆功能出现衰退；示踪实验显示衰老血液外泌体显著富集在海马脑区，引起神经细胞线粒体功能相关基因异常表达；此外，我们发现衰老血液外泌体miRNA的种类和含量发生显著变化,且可导致神经细胞线粒体功能缺失；基于此，我们提出假说，衰老血液外泌体miRNA通过调节线粒体功能介导神经退行性变化的发生。后续我们将从细胞和动物水平出发，探索血液外泌体miRNA介导神经退行性变化的具体分子机制，并开发基于外泌体miRNA改善神经退行性变化的新方法。

Neurodegeneration can cause a variety of age-related symptoms or diseases, however, the key pathogenic factors and molecular mechanisms that mediate neurodegeneration are still unclear. Aged blood can lead to organ aging and degeneration, but it is not clear which factors are involved. Exosomes are membrane vesicles released by a variety of different cells and distributed in the blood and other circulatory systems. The miRNAs transported by exosome regulate inter-cellular communication and participate in various life activities. In our previous study, we found that systemic administration of aged blood plasma or exosomes into young mice caused age-related cognitive, learning and memory impairments. Tracer experiment revealed that aged blood exosomes were enriched in hippocampus. Hippocampal gene expression sequencing found that the altered genes were significantly correlated with mitochondrial function.Sequencing analysis identified significant alteration of miRNA profiles between the blood exosomes of aged and young mice. In vivo and in vitro experiments found that aged exosomes or exosomal miRNA could lead to the loss of mitochondrial function in nerve cells. In this project, we hypothesize that blood exosomes and exosomal miRNAs may participate in the complex networks of cellular senescence in vitro and contribute to neurodegeneration in vivo. This project may uncover the involvement of blood exosomes and exosomal miRNA in the regulation of cellular senescence and demonstrate the potential role of them in biological processes and signaling pathways of aging and neurodegeneration.