Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), Gif-sur-Yvette, France.
Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), Gif-sur-Yvette, France.
Int Rev Cell Mol Biol. 2021;364:1-110. doi: 10.1016/bs.ircmb.2021.06.002. Epub 2021 Jul 12.
Aging-related diseases such as cancer can be traced to the accumulation of molecular disorder including increased DNA mutations and epigenetic drift. We provide a comprehensive review of recent results in mice and humans on modifications of DNA methylation and histone variants during aging and in cancer. Accumulated errors in DNA methylation maintenance lead to global decreases in DNA methylation with relaxed repression of repeated DNA and focal hypermethylation blocking the expression of tumor suppressor genes. Epigenetic clocks based on quantifying levels of DNA methylation at specific genomic sites is proving to be a valuable metric for estimating the biological age of individuals. Histone variants have specialized functions in transcriptional regulation and genome stability. Their concentration tends to increase in aged post-mitotic chromatin, but their effects in cancer are mainly determined by their specialized functions. Our increased understanding of epigenetic regulation and their modifications during aging has motivated interventions to delay or reverse epigenetic modifications using the epigenetic clocks as a rapid readout for efficacity. Similarly, the knowledge of epigenetic modifications in cancer is suggesting new approaches to target these modifications for cancer therapy.
衰老相关疾病，如癌症，可以追溯到分子紊乱的积累，包括 DNA 突变和表观遗传漂移的增加。我们提供了一个关于在衰老和癌症过程中 DNA 甲基化和组蛋白变体修饰的最新结果的全面综述。DNA 甲基化维持的累积错误导致全基因组 DNA 甲基化减少，重复 DNA 的抑制放松，局部高甲基化阻止肿瘤抑制基因的表达。基于特定基因组位点 DNA 甲基化水平定量的表观遗传时钟被证明是估计个体生物年龄的一个有价值的指标。组蛋白变体在转录调控和基因组稳定性方面具有特殊功能。它们在有丝分裂后染色质中的浓度往往会随着年龄的增长而增加，但它们在癌症中的作用主要取决于它们的特殊功能。我们对衰老过程中表观遗传调控及其修饰的理解的提高，促使人们利用表观遗传时钟作为有效性的快速读数，进行干预以延缓或逆转表观遗传修饰。同样，对癌症中表观遗传修饰的了解也为针对这些修饰进行癌症治疗提供了新的方法。
