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.

癌症等与衰老相关的疾病可以追溯到分子紊乱的积累，包括增加的 DNA 突变和表观遗传漂移。我们全面回顾了小鼠和人类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。DNA甲基化维持中的累积错误导致DNA甲基化的整体降低，重复DNA的放松抑制和局灶性高甲基化阻断肿瘤抑制基因的表达。基于量化特定基因组位点 DNA 甲基化水平的表观遗传时钟被证明是估计个体生物学年龄的有价值的指标。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。它们的浓度在老化的有丝分裂后染色质中趋于增加，但它们对癌症的影响主要取决于它们的特殊功能。我们对衰老过程中的表观遗传调控及其修饰的理解不断加深，这促使我们使用表观遗传时钟作为有效性的快速读数来延迟或逆转表观遗传修饰。同样，癌症中表观遗传修饰的知识也提示了针对这些修饰进行癌症治疗的新方法。