Genetic and Epigenetic Alterations of Genomes, de Duve Institute, Catholic University of Louvain, Brussels, Belgium.
Semin Cancer Biol. 2011 Dec;21(6):360-6. doi: 10.1016/j.semcancer.2011.09.003. Epub 2011 Sep 16.
Cellular senescence is eminently characterized by a permanent cell cycle arrest and the acquisition of morphological, physiological and epigenetic changes. The establishment of cellular senescence can occur in response to telomere attrition associated with cell turnover and ageing or following oncogene activation. Although seemingly two distinct phenomena, cellular senescence and cancer share similarly altered global epigenetic profiles comprising changes in DNA methylation, involving global hypomethylation of repetitive DNA sequences and regional hypermethylation of some gene promoters, and in histone post-translational modifications. As epigenetic and genetic alterations are likely to act synergistically in cancer, anomalous epigenetic marks acquired during ageing or in response to oncogene activation might play important roles in tumorigenesis and cancer progression. These potentially tumor-promoting epigenetic alterations include transcriptional repression of genes encoding tumor suppressors or developmentally regulated proteins, expression of non-coding repetitive RNAs and acquisition of distinct heterochromatin marks that may contribute to suppress cell death by reducing DNA damage response. Cellular senescence may thus be viewed as a double-edged sword that, although acting as a potent anti-proliferative barrier, may pave the way to tumorigenesis in senescence-escaping cells by altering their epigenetic make up.
细胞衰老的特征是细胞周期永久停滞和获得形态、生理和表观遗传变化。细胞衰老的建立可以响应与细胞更替和衰老相关的端粒磨损，或在致癌基因激活后发生。尽管细胞衰老和癌症似乎是两种截然不同的现象，但它们具有相似的全球表观遗传特征改变，包括 DNA 甲基化的改变，涉及重复 DNA 序列的全局低甲基化和一些基因启动子的局部高甲基化，以及组蛋白的翻译后修饰。由于表观遗传和遗传改变可能在癌症中协同作用，在衰老或对致癌基因激活的反应中获得的异常表观遗传标记可能在肿瘤发生和癌症进展中发挥重要作用。这些潜在的促进肿瘤的表观遗传改变包括肿瘤抑制基因或发育调节蛋白编码基因的转录抑制、非编码重复 RNA 的表达和获得独特的异染色质标记，这可能通过减少 DNA 损伤反应来抑制细胞死亡。因此，细胞衰老可以被视为一把双刃剑，尽管它作为一种有效的抗增殖屏障，但可能通过改变衰老逃逸细胞的表观遗传组成，为肿瘤发生铺平道路。
