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人类大脑衰老与细胞类型表观遗传身份的失调有关

Hyeonsoo Jeong^1,2, Isabel Mendizabal^3,4,5, Soojin V Yi^1,6

¹School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA 30332, USA.

bioRxiv : the preprint server for biology

|June 19, 2024

概括

衰老显著改变DNA甲基化模式,影响表观遗传漂移和细胞身份. 这些与年龄相关的变化与当前表观遗传时钟中使用的变化有所不同,突出了不同的分子机制.

科学领域:

基因组学就是基因组学.
表观遗传学在表观遗传学中,表观遗传学是指表观遗传学.
神经科学是一个神经科学.

背景情况:

随着年龄的增长,DNA甲基化发生变化 (表观遗传漂移),并作为衰老生物标志物.
连接表观遗传漂移和衰老生物标志物的分子机制仍然不清楚.
以前的研究受到小样本大小和组织异质性的限制.

研究的目的:

在数百万个CPG中调查与年龄相关的DNA甲基化变化.
在神经元与非神经元细胞 (寡 dendrocytes) 中区分甲基化模式.
澄清表观遗传漂移,细胞类型认同和表观遗传钟之间的关系.

主要方法:

对超过2000万个CPG的全基因组DNA甲基化分析.
在不同细胞类型 (神经元,寡细胞) 的广泛年龄范围内的分析.
统计建模以确定DNA甲基化变异的预测因素.

主要成果:

衰老是DNA甲基化变化的主要预测因素,超过了性别或疾病等因素.
表观遗传漂移显示了微妙的全基因组趋势,受CpG甲基化水平的影响.
细胞类型差异化的CpG容易发生与年龄相关的变化,细胞身份分歧.
表观遗传钟中的CpG在细胞类型上差异较小,不同于与年龄相关的变化.

结论:

与年龄相关的DNA甲基化变化影响表观遗传细胞类型的身份.
目前的表观遗传钟捕获的甲基化变化不同于那些驱动细胞身份分歧.
了解这些独特的机制对于衰老研究和生物标志物开发至关重要.

关键词:

通过DNA甲基化.衰老的衰老衰老的衰老细胞类型分化细胞类型分化表观遗传时钟的时间表.表观遗传失调是指表观遗传失调.

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