Oh Gabriel, Ebrahimi Sasha, Wang Sun-Chong, Cortese Rene, Kaminsky Zachary A, Gottesman Irving I, Burke James R, Plassman Brenda L, Petronis Art
Krembil Family Epigenetics Laboratory, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 250 College St. R130, Toronto, Ontario, M5T 1R8, Canada.
Institute of Systems Biology and Bioinformatics, National Central University, Chungli, 320, Taiwan.
Genome Biol. 2016 Apr 28;17:76. doi: 10.1186/s13059-016-0946-8.
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.
表观遗传漂变会逐渐增加衰老细胞DNA修饰图谱的变异性，但这种差异的最终结果仍不明确。在本研究中，我们探索了人类生命后期DNA修饰和转录的动态变化。
我们发现，与年轻个体相比，年龄较大的个体（>75岁）的脑组织在表观遗传和转录水平上彼此之间变得更加相似。个体间的表观遗传同化与大脑皮层和小脑之间相似度的增加同时发生，这表明存在潜在的脑细胞去分化现象。对患有阿尔茨海默病的双胞胎进行的DNA修饰分析揭示了神经退行性疾病中表观遗传同化加速的可能性。我们还观察到随着时间的推移，相邻的DNA修饰和转录组结构域的边界消失并合并。
矛盾的是，与年龄相关的表观遗传差异在生命后期转变为趋同。新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作为风险因素的疾病的起源。
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