增强器重新连接在肌肉干细胞衰老过程中调节炎症和细胞身份丧失
Changyou Shi1, Na Yang1, Evelyn Pizano1
1Laboratory of Genetics and Genomics, National Institute on Aging, NIH, Baltimore, Maryland, USA.
Aging cell
|November 15, 2025
概括
由于干细胞衰退,衰老会损害骨肌肉的再生. 这项研究揭示了肌肉干细胞 (MuSCs) 随着年龄的增长而发生的渐进分子变化,包括炎症和基因组改变,解释了功能损失.
科学领域:
- 老年学和再生医学的研究.
- 分子生物学和基因组学
- 干细胞生物学 干细胞生物学
背景情况:
- 器官再生随着年龄的增长而下降,通常是由于干细胞耗尽.
- 骨肌干细胞 (MuSCs) 显示与年龄相关的数量和功能损失,损害肌肉修复.
- 了解这些与年龄相关的变化对于开发恢复肌肉再生能力的干预措施至关重要.
研究的目的:
- 系统地描述不同年龄组和性别的单个小鼠MuSCs的表观基因组,转录基因组和3D基因组.
- 为了识别老化过程中逐渐发生的MuSCs中的分子变化.
- 为了将这些分子变化与肌肉再生中的功能缺陷相关联.
主要方法:
- 利用低输入多omics技术来分析个别的MuSCs.
- 将两性年轻,老年和老年老鼠进行比较.
- 整合了表观基因组,转录基因组和3D基因组数据,以提供对MuSC衰老的全面了解.
主要成果:
- 年轻的男性MuSCs表现出细胞周期基因表达的减少.
- 年龄较大的MuSCs,特别是男性的MuSCs,表现出早期的变化,如炎症增加和细胞身份丧失.
- 晚期衰老显示炎症加剧,增强器激活,3D基因组重新连接,以及与逆转录病毒表达和NFκB活性的联系.
结论:
- 渐进的分子转移,包括炎症和表观遗传/基因组改变,在老化过程中发生在MuSCs中.
- 这些与年龄相关的MuSCs变化有助于增殖和功能受损,解释了 reduced 骨肌肉再生.
- 这些发现突出了干细胞衰老和再生潜力的丧失所涉及的关键分子通路.
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