髓鞘可塑性在学习记忆的形成和提取中起着重要的作用。衰老中少突胶质细胞前体细胞（OPCs）分化障碍导致的髓鞘更新下降和少突胶质细胞（OLs）功能障碍导致的髓鞘变性均是导致脑衰老的重要因素。但是，谱系细胞出现这种衰老相关性功能改变的原因目前并不清楚。本项目前期结果发现，OPCs自噬障碍会导致小鼠提前出现脑衰老的表型包括认知功能障碍、OPCs老化、神经炎症、神经突触变性，并伴随着髓鞘变薄和其它衰老常见的髓鞘结构异常。另外，OPCs自噬障碍导致MBP蛋白水平增加，并形成蛋白多聚体。抑制自噬途径则导致OLN93细胞上MBP积聚。这些结果提示髓鞘组分蛋白经自噬降解。基于这些结果，我们提出本项目的假设：衰老导致的OPCs谱系细胞的自噬水平下调可能是导致髓鞘可塑性下降、髓鞘变性的关键因素，驱动脑衰老的重要原因。

Myelin plasticity is required for the consolidation and recall of memory. Both the declined myelin self-renewal caused by decreased differentiation of OPCs and myelin degeneration caused by OLs dysfunction contribute to the age-related cognitive decline with unknown mechanism. Our preliminary data revealed that deficient autophagy in OPCs results in cognitive deficits, senescence of OPCs，neuroinflammation and neurodegneration, comcomnitant with thinner myelin and abnormality in myelin structures which frequently seen in aged brains. Moreover, our preliminary results observed inhibition of autophagy caused accumulation of MBP in OLN93 cells. Deficient autophagy in OPCs resulted in accumulation of MBP aggregates in the brains of the mice. These results suggest that myelin components are degraded by autophagy. Therefore, the present project proposes that decreased levels of autophagy during aging results in senescence of OL lineage cells, which causes decreased myelin palsticity and myelin breakdown, eventually leading to the cognitive decline.