单细胞转录组学揭示了立体退化是与老年相关的肌功能障碍在小鼠和人类的关键贡献者
bioRxiv : the preprint server for biology
|February 20, 2025
概括
老年人与年龄相关的前体功能障碍 (ARVD) 与头发细胞衰老有关. 在前庭毛细胞中机制传导的恶化,而不是细胞损失,推动了这种下降.
科学领域:
- 老年学是一门学科.
- 神经科学是一个神经科学.
- 耳鼻喉科 耳鼻喉科 耳鼻喉科
背景情况:
- 与年龄相关的前体功能障碍 (ARVD) 在老年人中是常见的和衰弱的.
- ARVD的潜在原因和分子途径在很大程度上是未知的.
- 内耳中的机械敏感毛细胞 (HCs) 特别容易受到衰老过程的影响.
研究的目的:
- 为了研究前体毛细胞中衰老的分子和细胞机制.
- 为了比较前体和耳毛细胞中的衰老特征.
- 确定与年龄相关的前庭功能障碍的主要贡献者.
主要方法:
- 年轻和老老的小鼠前置毛细胞的单细胞RNA测序.
- 鼠标和人类老化前体毛细胞之间的比较转录组分析.
- 对前庭毛细胞束和功能进行了形态和功能评估.
主要成果:
- 衰老的前体毛细胞表现出普遍的衰老特征 (基因组不稳定性,线粒体功能障碍,蛋白质稳定性受损) 和细胞类型特定的特征.
- 这些衰老的特征,包括头发束的恶化和受损的机械传导,都保留在老人的前置头发细胞中.
- 玄关头发束退化和功能衰退在头发细胞损失之前,表明机械传导障碍是ARVD的主要驱动因素.
- 与耳毛细胞相比,前庭毛细胞的衰老效应不那么明显,这表明内耳内的衰老速度不同.
结论:
- 由于头发束退化导致机械传导的恶化是与年龄相关的前庭功能障碍的一个关键因素.
- 在老鼠和人类前体毛细胞中,共同的分子机制是衰老的基础.
- 垂体和耳的感觉上皮质以不同的速度衰老,垂体HC显示出相对的弹性.
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