Cellular senescence refers to a permanent and stable state of cell cycle exit. This process plays an important role in many cellular functions, including tumor suppression. It was first noted that senescence is associated with increased cell size in the early 1960s; however, how this contributes to permanent cell cycle exit was poorly understood until recently. In this review, we discuss new findings that identify increased cell size as not only a consequence but also a cause of permanent cell cycle exit. We highlight recent insights into how increased cell size alters normal cellular physiology and creates homeostatic imbalances that contribute to senescence induction. Finally, we focus on the potential clinical implications of these findings in the context of cell cycle arrest-causing cancer therapeutics and speculate on how tumor cell size changes may impact outcomes in patients treated with these drugs.

中文翻译：

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太大而不能失败：规模引起衰老的新证据

细胞衰老是指细胞周期退出的永久稳定状态。这一过程在许多细胞功能中发挥着重要作用，包括肿瘤抑制。早在 20 世纪 60 年代初，人们就首次注意到衰老与细胞尺寸增大有关。然而，直到最近，人们对这如何促进永久细胞周期退出还知之甚少。在这篇综述中，我们讨论了新的发现，这些发现确定细胞尺寸的增加不仅是永久细胞周期退出的结果，也是原因。我们重点介绍了最近对细胞大小增加如何改变正常细胞生理学并造成导致衰老诱导的稳态失衡的见解。最后，我们关注这些发现在导致细胞周期停滞的癌症治疗背景下的潜在临床意义，并推测肿瘤细胞大小的变化如何影响接受这些药物治疗的患者的结果。