Odum School of Ecology, University of Georgia, Athens, GA 30602, USA.
Savannah River Ecology Laboratory, University of Georgia, Aiken, SC 29802, USA.
Aging (Albany NY). 2021 Oct 13;13(19):22752-22771. doi: 10.18632/aging.203624.
Alterations to the epigenome are a hallmark of biological aging and age-dependent patterning of the DNA methylome ("epigenetic aging") can be modeled to produce epigenetic age predictors. Rates of epigenetic aging vary amongst individuals and correlate to the onset of age-related disease and all-cause mortality. Yet, the origins of epigenetic-to-chronological age discordance are not empirically resolved. Here, we investigate the relationship between aging, DNA methylation, and environmental exposures in Japanese medaka (). We find age-associated DNA methylation patterning enriched in genomic regions of low CpG density and that, similar to mammals, most age-related changes occur during early life. We construct an epigenetic clock capable of predicting chronological age with a mean error of 61.1 days (~8.4% of average lifespan). To test the role of environmental factors in driving epigenetic age variation, we exposed medaka to chronic, environmentally relevant doses of ionizing radiation. Because most organisms share an evolutionary history with ionizing radiation, we hypothesized that exposure would reveal fundamental insights into environment-by-epigenetic aging interactions. Radiation exposure disrupted epigenetic aging by accelerating and decelerating normal age-associated patterning and was most pronounced in cytosines that were moderately associated with age. These findings empirically demonstrate the role of DNA methylation in integrating environmental factors into aging trajectories.
表观基因组的改变是生物衰老的一个标志，并且 DNA 甲基化组（“表观遗传衰老”）的年龄依赖性模式可以被模拟，以产生表观遗传年龄预测因子。个体之间的表观遗传衰老率不同，并且与年龄相关疾病的发生和全因死亡率相关。然而，表观遗传与生理年龄差异的起源尚未得到经验性解决。在这里，我们研究了衰老、DNA 甲基化和环境暴露在日本青鳉（）中的关系。我们发现与年龄相关的 DNA 甲基化模式在低 CpG 密度的基因组区域中富集，并且与哺乳动物相似，大多数与年龄相关的变化发生在生命早期。我们构建了一个能够预测生理年龄的表观遗传时钟，平均误差为 61.1 天（~平均寿命的 8.4%）。为了测试环境因素在驱动表观遗传年龄变化中的作用，我们使青鳉暴露于慢性、环境相关剂量的电离辐射下。由于大多数生物体与电离辐射具有共同的进化历史，我们假设暴露将揭示环境与表观遗传衰老相互作用的基本见解。辐射暴露通过加速和减缓与年龄相关的正常模式来破坏表观遗传衰老，并且在与年龄中度相关的胞嘧啶中最为明显。这些发现从经验上证明了 DNA 甲基化在将环境因素整合到衰老轨迹中的作用。
