增强的线粒体亡信号损害C2C12肌细胞分化通过顺序传递通过细胞衰老后的细胞衰老
Fasih A Rahman1, Dylan J Hian-Cheong1, Kristen Boonstra1
1Department of Kinesiology and Health Sciences, University of Waterloo, Waterloo, ON, Canada.
Journal of cellular physiology
|January 12, 2024
概括
衰老会影响肌肉干细胞的分化. 肌细胞的顺序传递显示了细胞死亡和线粒体亡的增加,这表明线粒体功能障碍和与年龄相关的肌肉衰退之间存在联系.
科学领域:
- 细胞生物学 细胞生物学
- 衰老研究研究 衰老研究
- 线粒体生物学 线粒体生物学
背景情况:
- 衰老导致细胞功能障碍和再生能力下降,特别是在骨肌肉干细胞 (卫星细胞) 中.
- 现有的体外模型研究与年龄相关的肌肉功能障碍存在局限性.
- 骨肌肉质量的丧失,即萨尔科佩尼亚,是与卫星细胞损伤相关的关键衰老标志.
研究的目的:
- 调查线粒体亡途径在与年龄相关的骨肌肉细胞分化障碍中的作用.
- 建立一个新的骨肌肉衰老的体外模型,使用连续的肌细胞传递.
主要方法:
- 鼠标肌细胞的顺序传递产生模仿老化肌肉的高通道 (HP) 细胞.
- 对HP肌细胞的分化能力和细胞死亡的分析.
- 研究线粒体的亡信号,包括BAX转位,CYCS和AIFM1释放以及caspase-9激活.
主要成果:
- 顺序通过 (>20个通道) 显著减少了肌细胞分化和增加了细胞死亡.
- 惠普肌细胞通过BAX转位,CYCS/AIFM1释放和caspase-9激活显示了增强的线粒体介导的亡.
- 抑制线粒体外膜透性部分恢复了HP肌细胞的分化.
结论:
- 顺序传递在体外有效地模拟了与年龄相关的受损肌细胞分化.
- 线粒体的亡信号传递对老化肌细胞中观察到的分化减少有显著的贡献.
- 准线粒体亡途径可能为与年龄相关的肌肉功能障碍提供治疗潜力.
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