Walen Kirsten H
Viral and Rickettsial Disease Laboratory, California Department of Health Services, Richmond, CA 94801, USA.
In Vitro Cell Dev Biol Anim. 2006 Jul-Aug;42(7):216-24. doi: 10.1290/0603019.1.
Previously, it was found that senescent cells can undergo a modified cell cycle with mitotic cells as the end results. The major cycling events started with polyploidization, followed by depolyploidization to multinucleated cells (MNCs). These latter cells produced mononuclear offspring cells that could express mitotic cell divisions. In this report the emphasis is on late senescent fibroblasts that exhibited the senescence-associated change in cell morphology to large flat cells. Prior to live cell photography, flat cell cultures were maintained for months in the same culture flasks and therefore judged to be in a late senescent phase. All of the cellular events outlined above were present in these old cell cultures. Time lapse pictures showed movements of mitotic daughter cells away from each other and alignment of the chromosomes on the metaphase plate was visible in other mitotic cells. These data challenge the common view that cell senescence is irreversible and, therefore, an antitumor mechanism. A new finding was that the spike in polyploid cells in the near senescent phase consisted of cells with pairs of sister chromosomes from endoreduplication of DNA (two rounds of DNA synthesis and no mitosis). The lack of cells with 92 single chromosomes (e.g., G2 tetraploid cells) suggested that these polyploid cells also went through a changed cell cycle. The question now is whether these atypical polyploid cells are a subpopulation in senescence that can undergo the cycling from polyploidy to genome-reduced mitotic cells.
此前发现，衰老细胞可经历一种经过修饰的细胞周期，最终产生有丝分裂细胞。主要的循环事件始于多倍体化，随后是去多倍体化形成多核细胞（MNCs）。这些多核细胞产生的单核后代细胞能够进行有丝分裂。在本报告中，重点是晚期衰老成纤维细胞，其表现出衰老相关的细胞形态变化，变为大的扁平细胞。在进行活细胞摄影之前，扁平细胞培养物在同一培养瓶中维持了数月，因此被判定处于晚期衰老阶段。上述所有细胞事件在这些老龄细胞培养物中均有出现。延时摄影显示有丝分裂子代细胞彼此分离，并且在其他有丝分裂细胞中可见染色体在中期板上排列。这些数据挑战了细胞衰老不可逆且因此是一种抗肿瘤机制的普遍观点。一项新发现是，接近衰老阶段的多倍体细胞激增由因DNA核内复制（两轮DNA合成且无有丝分裂）而具有成对姐妹染色体的细胞组成。缺乏具有92条单染色体的细胞（例如G2四倍体细胞）表明这些多倍体细胞也经历了改变的细胞周期。现在的问题是，这些非典型多倍体细胞是否是衰老过程中的一个亚群，能够经历从多倍体到基因组减少的有丝分裂细胞的循环。
