Epigenetic assimilation in the aging human brain.
Epigenetic assimilation in the aging human brain.
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DOI：
10.1186/s13059-016-0946-8
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发表时间：
2016-04-28
期刊：
影响因子：
12.3
通讯作者：
Petronis A
中科院分区：
文献类型：
--
作者：
Oh G;Ebrahimi S;Wang SC;Cortese R;Kaminsky ZA;Gottesman II;Burke JR;Plassman BL;Petronis A
表观遗传漂变逐渐增加衰老细胞DNA修饰谱的变化，但这种分歧的结局仍然难以捉摸。在这项研究中，我们探索了DNA修饰和转录在人类生命后期的动力学。我们发现，与年轻人相比，老年人（>75岁）的脑组织在表观遗传和转录方面变得更加相似。个体间的表观遗传同化与大脑皮层和小脑之间的相似性增加同时发生，这表明潜在的脑细胞去分化。对阿尔茨海默病双胞胎的DNA修饰分析揭示了神经退行性疾病加速表观遗传同化的潜力。我们还观察到随着时间的推移，边界的丧失以及相邻DNA修饰和转录组结构域的合并。自相矛盾的是，在生命的后期阶段，依赖性的表观遗传分歧会转变为趋同。新近描述的表观遗传同化和组织去分化现象可能有助于我们更好地理解衰老的分子机制以及年龄是风险因素的疾病的起源。本文的在线版本（doi：10.1186/s13059-016-0946-8）包含补充材料，可供授权用户使用。
Epigenetic drift progressively increases variation in DNA modification profiles of aging cells, but the finale of such divergence remains elusive. In this study, we explored the dynamics of DNA modification and transcription in the later stages of human life. We find that brain tissues of older individuals (>75 years) become more similar to each other, both epigenetically and transcriptionally, compared with younger individuals. Inter-individual epigenetic assimilation is concurrent with increasing similarity between the cerebral cortex and the cerebellum, which points to potential brain cell dedifferentiation. DNA modification analysis of twins affected with Alzheimer’s disease reveals a potential for accelerated epigenetic assimilation in neurodegenerative disease. We also observe loss of boundaries and merging of neighboring DNA modification and transcriptomic domains over time. Age-dependent epigenetic divergence, paradoxically, changes to convergence in the later stages of life. The newly described phenomena of epigenetic assimilation and tissue dedifferentiation may help us better understand the molecular mechanisms of aging and the origins of diseases for which age is a risk factor. The online version of this article (doi:10.1186/s13059-016-0946-8) contains supplementary material, which is available to authorized users.