细胞衰老会损害肌的细胞外矩阵重塑,以应对机械卸载
Emma J Stowe1, Madelyn R Keller1, Brianne K Connizzo1
1Department of Biomedical Engineering, Boston University, Boston, Massachusetts, USA.
Aging cell
|July 23, 2024
概括
细胞衰老通过破坏细胞外矩阵平衡来促进与年龄相关的肌退化. 这项研究显示,衰老会改变肌对机械压力的反应,影响老年人群中的组织修复和功能.
科学领域:
- 生物医学工程 生物医学工程
- 肌肉骨生物学 肌肉骨生物学
- 细胞衰老 细胞衰老
背景情况:
- 与年龄相关的肌肉骨损伤,特别是肌病,对健康构成重大挑战.
- 与年龄相关的肌功能障碍背后的生物机制尚未完全理解,但细胞外矩阵 (ECM) 重塑失调与慢性退行有关.
- 衰老细胞是已知的组织病理的贡献者,释放一种与衰老相关的分泌表型 (SASP),可能导致ECM分解,但它们在肌ECM平衡中的特定作用尚不清楚.
研究的目的:
- 调查细胞衰老在肌细胞外基质 (ECM) 稳定性失调中的作用.
- 开发和利用一种在小鼠肌中诱导细胞衰老的新型体外模型,用于研究衰老细胞-ECM相互作用.
- 为了比较年轻,老年和诱导衰老肌对改变的机械刺激的ECM重塑反应.
主要方法:
- 在实验室模型的开发使用诱导的细胞衰老在小鼠肌的探索.
- 评估细胞衰老生物标志物,包括细胞循环停止,细胞亡抵抗和炎症反应.
- 在变化的机械负荷下对年轻,自然衰老和诱导衰老肌进行ECM重塑的比较分析.
主要成果:
- 诱导肌扩张显示了细胞衰老的多个生物标志物.
- 衰老和诱导衰老都独立改变了ECM相关的基因表达和减少了蛋白质合成.
- 在老化和诱导衰老肌中观察到持续的矩阵金属蛋白酶 (MMP) 活性,有利于降解而不是生产.
- 在老化和衰老的肌中都注意到了组织组成的变化.
结论:
- 细胞衰老在老化肌的改变机械反应中起着重要作用.
- 衰老有助于肌ECM恒温的失调,可能加剧与年龄相关的组织退化.
- 这些发现表明,细胞衰老是肌肉骨损伤的老年人群中观察到的不良临床结果的关键因素.
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