Ashraf Humza M, Fernandez Brianna, Spencer Sabrina L
bioRxiv. 2023 Mar 21:2023.03.18.533242. doi: 10.1101/2023.03.18.533242.
Senescence, a state of permanent cell-cycle withdrawal, is difficult to distinguish from quiescence, a transient state of cell-cycle withdrawal. This difficulty arises because quiescent and senescent cells are defined by overlapping biomarkers, raising the question of whether quiescence and senescence are truly distinct states. To address this, we used single-cell time-lapse imaging to distinguish slow-cycling quiescent cells from senescent cells after chemotherapy treatment, followed immediately by staining for various senescence biomarkers. We found that the staining intensity of multiple senescence biomarkers is graded rather than binary and primarily reflects the duration of cell-cycle withdrawal, rather than senescence per se. Together, our data suggest that quiescence and senescence are not distinct cellular states but rather fall on a continuum of cell-cycle withdrawal, where the intensities of canonical senescence biomarkers reflect the likelihood of cell-cycle re-entry.
衰老，即细胞周期永久停滞的一种状态，很难与静止状态区分开来，静止是细胞周期短暂停滞的一种状态。之所以会有这种困难，是因为静止细胞和衰老细胞是由重叠的生物标志物定义的，这就引发了一个问题：静止和衰老是否真的是不同的状态。为了解决这个问题，我们使用单细胞延时成像技术，在化疗治疗后将缓慢循环的静止细胞与衰老细胞区分开来，随后立即对各种衰老生物标志物进行染色。我们发现，多种衰老生物标志物的染色强度是分级的，而不是二元的，并且主要反映细胞周期停滞的持续时间，而不是衰老本身。总之，我们的数据表明，静止和衰老不是不同的细胞状态，而是处于细胞周期停滞的连续统一体上，其中典型衰老生物标志物的强度反映了细胞周期重新进入的可能性。
