脂质自噬在老年肌肉减少症骨骼肌脂肪沉积中的作用及机制研究

老年肌肉减少症（肌少症）增加老年人衰弱风险，加速失能进展。骨骼肌异位脂肪沉积从多方面影响骨骼肌质量及功能，促进肌少症的发生。脂质自噬参与脂代谢过程。AMPK在改善脂肪沉积以及自噬中担任重要角色。二甲双胍可激活AMPK。因此，拟通过构建肌少症的动物以及衰老的肌细胞模型，观察骨骼肌/肌细胞的脂质沉积、脂质自噬情况；通过病毒转染激活自噬，观察骨骼肌/肌细胞的脂质沉积情况以明确脂质自噬的作用；此外，二甲双胍干预上述模型，观察其对脂质自噬的改善作用。由上述证实：在增龄过程中，脂质自噬受损，导致骨骼肌异位脂肪沉积，进而影响骨骼肌的质量和功能，加重或诱发肌少症；当激活AMPK诱导脂质自噬时，可减少骨骼肌脂肪沉积，最终改善肌少症。项目首次将脂质自噬作为肌少症骨骼肌脂肪沉积的重要调控点，从AMPK-脂质自噬角度入手，探讨肌少症的可能机制，为深入研究以二甲双胍为代表的药物在改善肌少症中的可能机制提供新思路。

Sarcopenia increase the risk of the frailty, accelerate the disability. Skeletal muscle ectopic fat deposition in many ways affect skeletal muscle mass and function, promote the onset of muscle less. Lipophagy is involved in the lipid metabolism process。AMPK plays an important role in improving fat deposition and autophagy and Metformin activates AMPK. Therefore, we plan to build sarcopenia and aging muscle cell models to observe the skeletal muscle / muscle cell lipid deposition and lipophagy; Activate lipophagy to observe of skeletal muscle/muscle cell lipid deposition in order to make clear the role of lipophagy. In addition, Metformin intervene model above, observe its effect on the improvement of the lipophagy. By the above confirmed: In the process of age, lipophagy is damaged, cause ectopic fat deposition, in turn, affects the quality and function of the skeletal muscle, increase or inducing sarcopenia; When activated AMPK induced lipophagy can decrease skeletal muscle fat deposition, eventually improve sarcopenia. It may be of great significance to elucidate the mechanism of occurrence of skeletal muscle of ectopic fat deposition in sarcopenia; and provide new clues for the further study of Metformin as a representative of AMPK agonists in improving sarcopenia.