细胞衰老是一种细胞状态，其特征为生长停滞和对生长刺激激素的不敏感，伴随着染色质组织的大规模改变。衰老可以被一系列生理信号和病理性压力诱导，最初被认为是一种不可逆转的状态，与正常发育、伤口修复、肿瘤抑制和衰老有关。最近研究发现，在某些情况下细胞衰老是可以被逆转的，通过调节细胞的转录程序、抑制p53或H3K9me3、PDK1，和/或耗竭AP-1 等方式来引发退出。与衰老的逆转同时出现的是染色质组织的改变，最显著的是在致癌基因诱导的衰老中发现的衰老相关异染色质凝聚体（SAHF）的丧失。除了固定细胞成像，染色质构象捕获和多组学方法已被用于在不同的空间分辨率下研究衰老过程中的染色质重组。它们识别了SAHF形成的决定因素和其他区分不同衰老类型的关键特征。毫不奇怪，包括诱导时间、经历的压力类型和所涉及的细胞类型在内的多个因素，影响着衰老过程中染色质的整体重组。本文讨论了基因组三维组织的变化如何在衰老的不同阶段对转录的调控产生影响。特别地，我们讨论了异染色质和核膜介导的相互作用、基因表达的变化以及其他细胞控制机制的不同贡献。我们提出，在衰老过程中对染色质景观进行高分辨率的时间和空间分析将有助于识别不同衰老状态的早期标志，以帮助临床诊断的指导。© 2023. 作者。

Cellular senescence, a cell state characterized by growth arrest and insensitivity to growth stimulatory hormones, is accompanied by a massive change in chromatin organization. Senescence can be induced by a range of physiological signals and pathological stresses and was originally thought to be an irreversible state, implicated in normal development, wound healing, tumor suppression and aging. Recently cellular senescence was shown to be reversible in some cases, with exit being triggered by the modulation of the cell's transcriptional program by the four Yamanaka factors, the suppression of p53 or H3K9me3, PDK1, and/or depletion of AP-1. Coincident with senescence reversal are changes in chromatin organization, most notably the loss of senescence-associated heterochromatin foci (SAHF) found in oncogene-induced senescence. In addition to fixed-cell imaging, chromatin conformation capture and multi-omics have been used to examine chromatin reorganization at different spatial resolutions during senescence. They identify determinants of SAHF formation and other key features that differentiate distinct types of senescence. Not surprisingly, multiple factors, including the time of induction, the type of stress experienced, and the type of cell involved, influence the global reorganization of chromatin in senescence. Here we discuss how changes in the three-dimensional organization of the genome contribute to the regulation of transcription at different stages of senescence. In particular, the distinct contributions of heterochromatin- and lamina-mediated interactions, changes in gene expression, and other cellular control mechanisms are discussed. We propose that high-resolution temporal and spatial analyses of the chromatin landscape during senescence will identify early markers of the different senescence states to help guide clinical diagnosis.© 2023. The Author(s).