中枢胰岛素抵抗在2型糖尿病患者神经系统衰老过程中发挥重要作用，已成为近年研究热点，然而具体机制尚不明确。在前期实验中，我们发现胰岛素抵抗可引起神经细胞间代谢偶联障碍及糖酵解途径异常激活，最终导致神经元衰老加速；同时伴随着线粒体自噬相关特异蛋白CHOP、LC3-II及Pink1表达下降，提示线粒体自噬障碍可能在胰岛素抵抗加速神经元衰老过程中发挥重要作用，而自噬相关Pink1/Parkin通路可能在该过程中扮演重要角色。基于此，本课题拟在前期工作基础上，通过体内、外实验，进一步探索线粒体自噬Pink1/Parkin通路在胰岛素抵抗加速神经元衰老过程中的作用及其深层调控机制；并给予降糖药物干预以观察对线粒体自噬Pink1/Parkin通路及神经系统衰老的改善作用。本课题有望为胰岛素抵抗加速神经系统衰老提出新机制，为降糖药物在延缓神经系统衰老方面的应用奠定基础。

Insulin resistance (IR) is an important factor to accelerate the aging of neural cells in patients with type 2 diabetes (T2DM), which has been the hot topic in recent years. However, the underlying mechanism is unclear. Our previous work confirmed that IR caused accelerated neuron aging through disrupting the metabolic coupling between neurons and astrocytes and activating neural glycolysis. Furthermore, we found that the expressions of mitophagy related proteins CHOP, LC3-II and Pink1 were decreased. These results indicated that mitophagy might play an important role in the process of IR-induced neuron aging and mitophagy related Pink1/Parkin pathway might be the key point of this process. Based on the above, we aim to explore the role of mitophagy in IR-induced neuron aging and its underlying regulatory mechanism through in vitro and in vivo studies. Furthermore, we will use hypoglycemic agents as intervention to see their effects on mitophagy related Pink1/Parkin pathway and neuron aging. Our research might provide new idea on IR-induced aging of nervous system in diabetic patients, and shed light on the application of hypoglycemic drugs in the treatment of aging-related nervous system diseases.