Institute of Cytology, Russian Academy of Sciences, St. Petersburg, Russia.
Cell Cycle. 2009 Dec 15;8(24):4112-8. doi: 10.4161/cc.8.24.10215. Epub 2009 Dec 1.
Cellular senescence is currently viewed as a response to DNA damage. In this report, we showed that non-damaging agents such as sodium butyrate-induced p21 and ectopic expression of either p21 or p16 cause cellular senescence without detectable DNA breaks. Nevertheless, senescent cells displayed components of DNA damage response (DDR) such as gammaH2AX foci and uniform nuclear staining for p-ATM. Importantly, there was no accumulation of 53BP1 in gammaH2AX foci of senescent cells. Consistently, comet assay failed to detect DNA damage. Rapamycin, an inhibitor of mTO R, which was shown to suppress cellular senescence, decreased gammaH2AX foci formation. Thus, cellular senescence leads to activation of atypical DDR without detectable DNA damage. Pseudo-DDR may be a marker of general over-activation of senescent cells.
细胞衰老目前被认为是对 DNA 损伤的一种反应。在本报告中，我们表明，非损伤性试剂，如丁酸钠诱导的 p21 和异位表达 p21 或 p16，会导致细胞衰老，而不会检测到 DNA 断裂。然而，衰老细胞显示出 DNA 损伤反应 (DDR) 的成分，如 γH2AX 焦点和 p-ATM 的均匀核染色。重要的是，在衰老细胞的 γH2AX 焦点中没有 53BP1 的积累。同样，彗星试验未能检测到 DNA 损伤。雷帕霉素，一种 mTOR 的抑制剂，被证明可以抑制细胞衰老，减少 γH2AX 焦点的形成。因此，细胞衰老导致非典型 DDR 的激活，而不会检测到 DNA 损伤。伪 DDR 可能是衰老细胞普遍过度激活的标志。
