甜菜碱的甲基供体作用及其对中老年人肌肉衰减的影响和机制探讨

Sarcopenia is the main cause for high incidence of disability and death in the elderly. Betaine has been used in animal feeds to improve lean mass for a long time, but the role of betaine on muscle mass in humans is not clear. In the baseline survey of “Guangzhou Nutrition and Health Study”, we found that higher serum betaine correlated to larger proportion of lean mass (LM%), which suggest that betaine may help to prevent sarcopenia in the elderly. We carry out the present study in an established elderly cohort “Guangzhou Nutrition and Health Study”, which has been follow-up for 6 years. In this study, we will keep follow-up for 3 years, and explore the association of betaine with sarcopenia and the change of lean mass during a total 9-year period. Additionally, our previous research also demonstrated that betaine acts as a methyl donor in many pathways, including the methylation of homocysteine. Therefore, we use aged sarcopenia mice model to investigate the improved effects of betaine on muscle and to explore the protection effect through lowering homocysteine and the activation of IGF-1/PI3K/AKt/mTOR pathway. The results of this research may offer a new approach for preventing sarcopenia in the elderly.

肌肉衰减综合征是引起我国老年人失能、死亡风险增加的重要原因。甜菜碱添加到动物饲料用于提高瘦肉率的应用已久，但对人体肌肉的作用不明。我们的横断面调查发现血清甜菜碱水平高的中老年人身体瘦组织的构成比较高，提示甜菜碱有利于减缓中老年人肌肉衰减。我们首先利用已经建立并完成6年随访的“广州居民营养与健康研究队列”以及正在执行的国自然项目（81472966）中获得的数据，继续对队列随访3年以探讨甜菜碱与中老年人肌肉衰减的关联及与9年随访期间肌肉衰减变化的关系；此外，我们前期研究证实甜菜碱具有降同型半胱氨酸（Hcy）作用，我们通过老年肌肉衰减小鼠模型，确证甜菜碱干预对小鼠肌肉衰减的改善效果；并进一步探讨甜菜碱通过降Hcy及其硫代内酯，从而激活IGF-1/PI3K/Akt/mTOR信号通路，促进肌纤维形成及肌蛋白质合成，阐明甜菜碱减缓肌肉衰减的机制。本研究将为中老年人肌肉衰减防制开发新的食物资源开辟新途径

肌肉衰减综合征是引起我国老年人失能、死亡风险增加的重要原因。甜菜碱添加到动物饲料用于提高瘦肉率的应用已久，但对人体肌肉的作用不明。我们的横断面调查发现血清甜菜碱水平高的中老年人身体瘦组织的构成比较高，提示甜菜碱有利于减缓中老年人肌肉衰减。在本项目中，我们首先利用“广州居民营养与健康研究队列”探讨甜菜碱与中老年人肌肉衰减的关联及与随访期间肌肉衰减变化的关系。而后，通过老年肌肉衰减小鼠模型，确证甜菜碱干预对小鼠肌肉衰减的改善效果；并进一步探讨甜菜碱减缓肌肉衰减的机制。通过人群研究，我们明确了甜菜碱的摄入量和血清水平能维持中老年人的肌肉量，且在长期（6.2年）的随访中，随着甜菜碱的膳食摄入以及血清水平的增加，中老年人肌肉量的丢失量下降，肌衰症的发生风险也降低。通过动物实验，我们明确了甜菜碱干预能够增加老年小鼠的骨骼肌质量、力量和功能，维持骨骼肌的形态学，并且能够促进老年小鼠的肌蛋白合成；其中调控肌肉质量与功能的关键分子通路mTORC1信号通路在干预后发生了显著的上调。通过体外实验，我们发现甜菜碱能通过蛋氨酸循环，升高体内SAM水平，从而减轻mTORC1蛋白上游的复合体SAMTOR-KICSTOR-CASTOR抑制mTORC1信号通路，从而促进肌蛋白质合成，增加肌肉质量、力量和功能。本研究将为中老年人肌肉衰减防制开发新的食物资源开辟新途径.