Kochmanski Joseph, Montrose Luke, Goodrich Jaclyn M, Dolinoy Dana C
Environmental Health Sciences.
Nutritional Sciences, School of Public Health, University of Michigan, Washington Heights, Ann Arbor, Michigan 48109.
Toxicol Sci. 2017 Apr 1;156(2):325-335. doi: 10.1093/toxsci/kfx005.
Epigenetic drift and age-related methylation have both been used in the literature to describe changes in DNA methylation that occurs with aging. However, ambiguity remains regarding the exact definition of both of these terms, and neither of these fields of study explicitly considers the impact of environmental factors on the aging epigenome. Recent twin studies have demonstrated longitudinal, pair-specific discordance in DNA methylation patterns, suggesting an effect of the environment on age-related methylation and/or epigenetic drift. Supporting this idea, other new reports have shown clear environment- and toxicant-mediated shifts away from the baseline rates of age-related methylation and epigenetic drift within an organism, a process we now term "environmental deflection." By defining and delineating environmental deflection, this contemporary review aims to highlight the effects of specific toxicological factors on the rate of DNA methylation changes that occur over the life course. In an effort to inform future epigenetics-based toxicology studies, a field of research now classified as toxicoepigenetics, we provide clear definitions and examples of "epigenetic drift" and "age-related methylation," summarize the recent evidence for environmental deflection of the aging epigenome, and discuss the potential functional effects of environmental deflection.
表观遗传漂变和与年龄相关的甲基化在文献中都被用来描述随着衰老而发生的DNA甲基化变化。然而,这两个术语的确切定义仍不明确,而且这两个研究领域都没有明确考虑环境因素对衰老表观基因组的影响。最近的双胞胎研究表明,DNA甲基化模式存在纵向的、特定于双胞胎对的不一致性,这表明环境对与年龄相关的甲基化和/或表观遗传漂变有影响。支持这一观点的是,其他新报告显示,在生物体内,环境和毒物介导的变化明显偏离了与年龄相关的甲基化和表观遗传漂变的基线速率,我们现在将这一过程称为“环境偏移”。通过定义和描述环境偏移,这篇当代综述旨在强调特定毒理学因素对生命过程中发生的DNA甲基化变化速率的影响。为了为未来基于表观遗传学的毒理学研究(现在被归类为毒理表观遗传学的一个研究领域)提供信息,我们给出了“表观遗传漂变”和“与年龄相关的甲基化”的明确定义及示例,总结了衰老表观基因组环境偏移的最新证据,并讨论了环境偏移的潜在功能影响。