Emerging evidence published over the past decade has highlighted the role of DNA methylation in skeletal muscle function and health, including as an epigenetic transducer of the adaptive response to exercise. In this review, we aim to synthesize the latest findings in this field to highlight: (1) the shifting understanding of the genomic localization of altered DNA methylation in response to acute and chronic aerobic and resistance exercise in skeletal muscle (e.g., promoter, gene bodies, enhancers, intergenic regions, un-annotated regions, and genome-wide methylation); (2) how these global/regional methylation changes relate to transcriptional activity following exercise; and (3) the factors (e.g., individual demographic or genetic features, dietary, training history, exercise parameters, local epigenetic characteristics, circulating hormones) demonstrated to alter both the pattern of DNA methylation after exercise, and the relationship between DNA methylation and gene expression. Finally, we discuss the changes in non-CpG methylation and 5-hydroxymethylation after exercise, as well as the importance of emerging single-cell analyses to future studies—areas of increasing focus in the field of epigenetics. We anticipate that this review will help generate a framework for clinicians and researchers to begin developing and testing exercise interventions designed to generate targeted changes in DNA methylation as part of a personalized exercise regimen.

过去十年发表的新证据强调了 DNA 甲基化在骨骼肌功能和健康中的作用，包括作为运动适应性反应的表观遗传转导器。在这篇综述中，我们的目的是综合该领域的最新发现，以强调：（1）对骨骼肌中急性和慢性有氧运动和抗阻运动中 DNA 甲基化改变的基因组定位的理解的转变（例如，启动子、基因）体、增强子、基因间区域、未注释区域和全基因组甲基化）； (2) 这些全球/区域甲基化变化与运动后的转录活性有何关系； (3) 被证明可以改变运动后 DNA 甲基化模式以及 DNA 甲基化与基因之间关系的因素（例如，个体人口统计或遗传特征、饮食、训练历史、运动参数、局部表观遗传特征、循环激素）表达。最后，我们讨论了运动后非 CpG 甲基化和 5-羟甲基化的变化，以及新兴单细胞分析对未来研究的重要性——这些领域是表观遗传学领域日益关注的领域。我们预计这次审查将有助于为临床医生和研究人员建立一个框架，以开始开发和测试旨在产生 DNA 甲基化有针对性的变化的运动干预措施，作为个性化运动方案的一部分。