为明确Bmi-1延缓炎性衰老是否通过胞浆p16INK4a直接与p-STAT3(S727)和/或GRIM-19结合，阻止p-STAT3(S727)与GRIM-19复合物向线粒体转位，抑制线粒体电子传递链复合体导致线粒体功能障碍和损伤，Bmi-1缺失是否致线粒体自噬清除力下降，升高的线粒体ROS和DAMPs活化NLRP3炎症小体引起活性IL-1beta增加。利用Bmi-1和p16INK4a基因缺失小鼠及细胞，经相关分子或药物干预，通过Co-IP和邻位连接技术研究蛋白质结合程度及亚细胞定位，辨认生物信息预测的结合的结构域及氨基酸残基；通过Seahorse生物能量测定仪检测线粒体功能；利用细胞及分子生物学、组织病理学方法观察炎性衰老改善，探讨Bmi-1维持线粒体自噬和抑制炎症小体活化的机制；观察生理性衰老小鼠、细胞及人血样是否具有同上炎性衰老机制。本研究将为临床防治炎性衰老疾病提供新的靶标和依据。

To determine whether Bmi-1 delayed inflammaging by cytoplasmic p16INK4a binding p-STAT3(S727) and/or GRIM-19, preventing translocation of p-STAT3(S727) and GRIM-19 complex to the mitochondria, inhibiting the role of mitochondrial electron transfer chain complex which led to mitochondrial dysfunction and damage, and whether the deletion of Bmi-1 caused the decrease of mitochondrial autophagy scavenging ability, elevated mitochondrial ROS and DAMPs activated NLRP3 inflammasome causing increased activity of IL-1beta. Bmi-1 and p16INK4a deficiency mice and cells will be used with treatments of associated molecules or drugs to investigate the degree of protein binding and subcellular localization by Co-IP and Proximity Ligation Assay, to identify the binding domain and amino acid residues predicted by bioinformatics base; Mitochondrial function will be measured by Seahorse Bioenergetics; The improvement of inflammaging will be observed using cell and molecular biology, histopathology to explore the mechanism of action of Bmi-1 to maintain mitochondrial autophagy and inhibit the activation of inflammasome; Physiological aging mice, cells and human blood samples will be observed with the same mechanism of inflammaging as described above. This study will provide a new target and basis for clinical prevention and treatment of inflammaging related diseases.