复制性衰老是ATM驱动的,可逆的,并通过ATM在normoxia的过度激活来加速
Alexander Stuart1, Titia de Lange1
1Laboratory for Cell Biology and Genetics, Rockefeller University, New York, USA.
bioRxiv : the preprint server for biology
|July 9, 2024
概括
由ATM激酶驱动的编程细胞衰老,限制了癌症. 这项研究揭示了ATM抑制可以逆转衰老,并且低氧通过ROS减少ATM活动来延长细胞寿命.
科学领域:
- 细胞衰老 细胞衰老
- 端粒生物学 端粒生物学
- 预防癌症 预防癌症
背景情况:
- 编程的端粒缩短会诱导复制性衰老,这是对瘤发生的关键障碍.
- 了解衰老的精确分子触发器和调节器对于癌症研究至关重要.
研究的目的:
- 为了阐明唯一的酶,负责复制性衰老的诱导.
- 为了研究衰老逆转的可能性.
- 确定在生理氧气水平下延长细胞寿命背后的机制.
主要方法:
- 利用ATM激酶抑制 (ATMi) 和TRF2过度表达.
- 评估ATR信号与ATMi一起使用.
- 在20%和低 (生理) 氧水平下比较细胞反应.
- 研究了活性氧物种 (ROS) 和N-乙半氨酸 (NAC) 的作用.
主要成果:
- ATM 激酶仅仅负责诱导复制性衰老;ATR 信号没有贡献.
- 抑制ATM可以逆转衰老,使正常细胞在细胞子集中的分裂成为可能.
- 在低氧的情况下延长细胞寿命是由于ATM活动减少,由ROS诱导的ATM二元交联介导.
结论:
- ATM 激酶是复制性衰老的唯一驱动因素.
- 细胞衰老是一种潜在的可逆状态.
- 氧气水平和ROS显著调节ATM活动和端粒驱动的瘤抑制.
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