解读免疫景观改造揭示了同步肌肉和骨衰老的潜在机制
Pengbin Yin1,2, Ming Chen1,2, Man Rao1,2,3
1Senior Department of Orthopedics, The Fourth Medical Center of PLA General Hospital, Beijing, 100048, China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|December 13, 2023
概括
老龄化同步影响骨和肌肉. 研究人员发现了脂质相关的巨细胞 (TREM2+ Macs),并确定了一条涉及肌肉细胞外体的通信通路,该通路通过T细胞和巨细胞将肌肉退化与骨质损失联系起来.
科学领域:
- 老年学是一门学科.
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 骨和肌肉衰老经常同时发生,但机制尚不清楚.
- 了解肌肉骨组织的共同衰老过程对于开发干预措施至关重要.
研究的目的:
- 研究人类骨和肌肉同步衰老背后的分子机制.
- 确定关键的细胞参与者和参与这些组织年龄相关变化的信号通路.
主要方法:
- 人类肌肉和骨组织的单细胞RNA测序.
- 在老化组织中分析转录动态和细胞表型.
- 研究细胞间通信通路,包括外体介导信号传递.
主要成果:
- 在衰老的肌肉和骨中识别TREM2+巨细胞,表达与衰变和骨损失相关的基因 (例如SPP1).
- 观察到一种常见的转向促炎性CD4+T细胞 (NFKB1-激活),具有组织特异化 (肌肉中的Th1,骨中的Th17).
- 退化的肌细胞释放含有BAG6的外体,与Th17细胞相互作用,对CD6进行上调,然后向TREM2+巨细胞发出信号,增加SPP1转录,将肌肉和骨衰老联系起来.
结论:
- 在与衰老相关的肌肉和骨变化中,TREM2+巨细胞和特定的T细胞子集起着保留的作用.
- 从退化的肌细胞到骨Th17细胞,随后到TREM2+巨细胞的新型外体细胞介导通信途径同步了衰老过程.
- 血清外体BAG6水平与骨矿物质密度负相关,支持其在肌肉骨老化同步中的作用.
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