转录信息流中的衰变是细胞衰老的标志
bioRxiv : the preprint server for biology
|November 24, 2025
概括
老龄化导致基因调节信息传输的下降,影响细胞通信网络. 恢复关键的转录因子活性可能会使这些老化的网络复苏.
科学领域:
- 基因组学就是基因组学.
- 系统生物学 系统生物学
- 信息理论 信息理论
背景情况:
- 衰老的特点是细胞功能障碍,但根本的调节原则尚未完全理解.
- 分子衰老涉及破坏了协调细胞活动的通信网络.
- 基因调控依赖于转录因子 (TFs) 和基因 (TGs) 之间的复杂相互作用.
研究的目的:
- 使用信息理论量化基因调节网络的与年龄相关的变化.
- 为了确定驱动沟通衰退的机制在老化.
- 探索潜在的干预措施,以复兴老化的监管网络.
主要方法:
- 模拟TF-TG交互作为一个多输入多输出通信通道.
- 将一个分析可处理的概率模型应用于来自十种组织的单细胞RNA测序数据.
- 量化相互信息,以测量与年龄相关的信息丢失在基因调节.
主要成果:
- 在所有分析的组织中,TF和TG之间的相互信息随着年龄的增长而显著下降.
- 老龄化主要通过输入分配不匹配 (协调TF活动的损失) 而不是道腐败来降低监管通信.
- 网络集中度的增加和反动机的丧失有助于降低网络在老化的稳定性.
结论:
- 监管信息传输的丧失是衰老的一个标志.
- 衰老通过受损的TF协调而不是TF功能障碍来破坏基因调节.
- 针对特定TFs的有针对性的上调可以恢复年轻的信息传输和基因表达,这表明了复苏的途径.
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