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年龄和生命早期的逆境塑造了子组织间表观基因组的异质性

Baptiste Sadoughi^1,2, Rachel Petersen³, Sam K Patterson^4,5,6

¹School of Life Sciences, Arizona State University; Tempe, AZ, USA.

bioRxiv : the preprint server for biology

|August 12, 2025

概括

生命早期的逆境 (ELA) 和衰老会影响整个组织的DNA甲基化. 埃拉留下了一个独特的表观遗传特征,与衰老不同,但与衰老有关,影响健康和疾病风险.

科学领域:

表观遗传学在表观遗传学中,表观遗传学是指表观遗传学.
比较生物学的比较生物学
健康和疾病的发育起源 (DOHaD)

背景情况:

年龄和生命早期的逆境 (ELA) 是关键的健康决定因素.
有限的多组织数据阻碍了对年龄和ELA之间的共享生理机制的理解.
研究这些机制对于理解衰老和疾病病因至关重要.

研究的目的:

调查年龄和ELA是否针对多种组织中类似的生理机制.
在14个组织中分析与年龄和ELA相关的DNA甲基化 (DNAm) 概况.
探索ELA在组织中的协调影响及其与与年龄相关的表观遗传变化的关系.

主要方法:

从237只 rhesus macaque的14个组织中生成了DNA甲基化 (DNAm) 档案.
使用了具有自然发生的早期生命逆境 (ELA) 记录的动物.
开发和应用特定组织的表观遗传钟来评估表观遗传衰老速度.

主要成果:

年龄相关的DNAm变异主要取决于组织,但表观遗传衰老速度在个体内是一致的.
埃拉对DNAm loci的影响依赖于逆境,并在组织之间显示协调的影响.
晚年老化病 (ELA) 影响了许多与衰老相同的位置,但具有不同的作用方向,表明复杂的相互作用而不是均的加速.

结论:

生命早期的逆境 (ELA) 建立了一个协调的,跨越组织的表观遗传特征.
这种ELA特征与与年龄相关的表观遗传变化不同,但与之交织在一起.
这些发现有助于更好地理解早期环境如何影响衰老和疾病易感性的分子途径.

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