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甲状腺激素受体α激发性线粒体功能障碍的异常表达导致老年小鼠的萨尔科佩尼亚

Yunlu Sheng¹, Xiaoxia Zhu¹, Lijun Wei¹

¹Division of Geriatric Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, People’s Republic of China.

|April 21, 2024

概括

甲状腺激素受体α (TRα) 在衰老的骨肌肉下降会损害线粒体功能和肌肉发育. 恢复TRα可以改善线粒体活动和肌肉健康.

科学领域:

细胞生物学细胞生物学
肌肉生理学肌肉生理学
内分泌学在内分泌学.

背景情况:

老化骨肌肉表现出受损的线粒体动力学和线粒体衰变.
甲状腺激素受体α (TRα) 表达随着年龄的增长而下降,可能会影响肌肉功能.
将TRα与与年龄相关的骨肌肉退化联系在一起的机制尚未完全理解.

研究的目的:

研究TRα在调节线粒体动力学,线粒体和骨肌肉衰老中的肌体生成中的作用.
阐明TRα在衰老过程中影响骨肌肉健康的分子机制.

主要方法:

对老年小鼠TRα表达和相关标记物的分析.
在C2C12髓母细胞细胞系中进行TRα功能丧失和增益研究.
评估肌源性调节剂,线粒体标记物,线粒体动力学和活性氧物种 (ROS).

主要成果:

在老年小鼠中,TRα表达的减少与肌原性调节剂 (Myf5,MyoD1),线粒体的标记物 (Pink1,LC3II/I,p62) 和线粒体动力学因子 (Mfn1,Opa1) 的减少相关.
在C2C12细胞中的TRα沉默降低了这些标记物的调节,减少了线粒体活动和呼吸能力,并增加了ROS和线粒体损伤.
过度表达TRα上调了这些标记物,增强了线粒体活动和数量.

结论:

TRα在协调线粒体动力学,线粒体和肌肉生成方面发挥着至关重要的作用.
降低TRα表达有助于骨肌肉衰退在衰老过程中.
对于与年龄相关的肌肉功能障碍,TRα是一种潜在的治疗点.

关键词:

老化的老鼠.线粒体功能障碍线粒体功能障碍线粒细胞衰变 (mitophagy) 是一种神经衰变的过程.这是骨肌肉.甲状腺激素受体 α α 甲状腺激素受体

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