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首页> 外文期刊>Cell metabolism >Aging-Dependent Demethylation of Regulatory Elements Correlates with Chromatin State and Improved beta Cell Function
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Aging-Dependent Demethylation of Regulatory Elements Correlates with Chromatin State and Improved beta Cell Function

机译：调节元件的衰老依赖性去甲基化与染色质状态和改善的β细胞功能相关

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摘要

Aging is driven by changes of the epigenetic state that are only partially understood. We performed a comprehensive epigenomic analysis of the pancreatic beta cell, key player in glucose homeostasis, in adolescent and very old mice. We observe a global methylation drift resulting in an overall more leveled methylome in old b cells. Importantly, we discover targeted changes in the methylation status of b cell proliferation and function genes that go against the global methylation drift, are specific to b cells, and correlate with repression of the proliferation program and activation of metabolic regulators. These targeted alterations are associated with specific chromatin marks and transcription factor occupancy in young b cells. Strikingly, we find b cell function improved in aged mice, as predicted by the changes in methylome and transcriptome. Thus, aging of terminally differentiated cells in mammals is not always coupled to functional decline.
机译：衰老是由表观遗传状态的变化驱动的，这种变化只有部分被理解。我们对青春期和非常老龄小鼠的胰岛β细胞（葡萄糖稳态的关键因素）进行了全面的表观基因组学分析。我们观察到整体甲基化漂移导致旧b细胞中总体甲基化水平更高。重要的是，我们发现b细胞增殖的甲基化状态的定向变化和功能基因与全球甲基化漂移背道而驰，这些基因对b细胞特异，并且与增殖程序的抑制和代谢调节剂的激活相关。这些有针对性的改变与年轻b细胞中特定的染色质标记和转录因子占用有关。令人惊讶地，我们发现，如甲基化组和转录组的变化所预测的，老年小鼠的b细胞功能得到了改善。因此，哺乳动物中终末分化细胞的衰老并不总是与功能下降有关。

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