Epigenetics, DNA damage, and aging.
Epigenetics, DNA damage, and aging.
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DOI：
10.1172/jci158446
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发表时间：
2022-08-15
影响因子：
15.9
通讯作者：
Dong, Xiao
中科院分区：
文献类型：
--
作者：
Soto-Palma, Carolina;Niedernhofer, Laura J.;Faulk, Christopher D.;Dong, Xiao
在人的一生中，基因组完整性受到侵蚀，导致几种类型的染色质变化的丰度增加。DNA损伤（对核苷酸的化学扰动）的丰度随着年龄的增长而增加，基因组突变的数量以及由这些损伤的复制或转录引起的转录破坏的数量也随着年龄的增长而增加。在表观遗传水平上，精确的DNA甲基化模式退化，可能导致基因表达的随机变异越来越多。类似地，组蛋白修饰的严格调控开始瓦解。由这些机制引起的基因组不稳定性允许转座子元件再激活和再动员、进一步突变、基因失调和细胞质染色质片段。这种累积的基因组不稳定性促进细胞信号传导事件，这些事件驱动细胞命运决定和细胞外通信，已知这些事件破坏组织稳态和再生。在这篇综述中，我们关注与年龄相关的表观遗传变化及其与年龄相关的基因组变化的相互作用，这些变化引发了这些事件。
Over the course of a human lifespan, genome integrity erodes, leading to an increased abundance of several types of chromatin changes. The abundance of DNA lesions (chemical perturbations to nucleotides) increases with age, as does the number of genomic mutations and transcriptional disruptions caused by replication or transcription of those lesions, respectively. At the epigenetic level, precise DNA methylation patterns degrade, likely causing increasingly stochastic variations in gene expression. Similarly, the tight regulation of histone modifications begins to unravel. The genomic instability caused by these mechanisms allows transposon element reactivation and remobilization, further mutations, gene dysregulation, and cytoplasmic chromatin fragments. This cumulative genomic instability promotes cell signaling events that drive cell fate decisions and extracellular communications known to disrupt tissue homeostasis and regeneration. In this Review, we focus on age-related epigenetic changes and their interactions with age-related genomic changes that instigate these events.
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影响因子：
3.7
作者：
Newman MR;Sykes PJ;Blyth BJ;Bezak E;Lawrence MD;Morel KL;Ormsby RJ
通讯作者：
Ormsby RJ
影响因子：
3.7
作者：
Sidler C;Li D;Wang B;Kovalchuk I;Kovalchuk O
通讯作者：
Kovalchuk O
影响因子：
2.8
作者：
Sordillo JE;Lange NE;Tarantini L;Bollati V;Zanobetti A;Sparrow D;Vokonas P;Schwartz J;Baccarelli A;Demeo D;Litonjua AA
通讯作者：
Litonjua AA
影响因子：
2.4
作者：
Awwad SW;Ayoub N
通讯作者：
Ayoub N