Resistance training (RT) dynamically alters the skeletal muscle nuclear DNA methylome. However, no study has examined if RT affects the mitochondrial DNA (mtDNA) methylome. Herein, ten older, Caucasian untrained males (65 ± 7 y.o.) performed six weeks of full-body RT (twice weekly). Body composition and knee extensor torque were assessed prior to and 72 h following the last RT session. Vastus lateralis (VL) biopsies were also obtained. VL DNA was subjected to reduced representation bisulfite sequencing providing excellent coverage across the ~16-kilobase mtDNA methylome (254 CpG sites). Biochemical assays were also performed, and older male data were compared to younger trained males (22 ± 2 y.o., n = 7, n = 6 Caucasian & n = 1 African American). RT increased whole-body lean tissue mass (p = .017), VL thickness (p = .012), and knee extensor torque (p = .029) in older males. RT also affected the mtDNA methylome, as 63% (159/254) of the CpG sites demonstrated reduced methylation (p < .05). Several mtDNA sites presented a more “youthful” signature in older males after RT in comparison to younger males. The 1.12 kilobase mtDNA D-loop/control region, which regulates replication and transcription, possessed enriched hypomethylation in older males following RT. Enhanced expression of mitochondrial H- and L-strand genes and complex III/IV protein levels were also observed (p < .05). While limited to a shorter-term intervention, this is the first evidence showing that RT alters the mtDNA methylome in skeletal muscle. Observed methylome alterations may enhance mitochondrial transcription, and RT evokes mitochondrial methylome profiles to mimic younger men. The significance of these findings relative to broader RT-induced epigenetic changes needs to be elucidated.

中文翻译：

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阻力训练使衰老人类骨骼肌中的线粒体甲基化组恢复活力

阻力训练 (RT) 动态改变骨骼肌核 DNA 甲基化组。然而，没有研究检查 RT 是否影响线粒体 DNA (mtDNA) 甲基化组。在此，十名年龄较大、未受过训练的白人男性（65 ± 7 岁）进行了六周的全身放疗（每周两次）。在最后一次 RT 会议之前和之后 72 小时评估身体成分和膝关节伸肌扭矩。还获得了股外侧肌 (VL) 活组织检查。VL DNA 进行了减少代表性的亚硫酸氢盐测序，提供了对 ~16 千碱基 mtDNA 甲基化组（254 个 CpG 位点）的出色覆盖。还进行了生化分析，并将年长男性数据与受过训练的年轻男性（22 ± 2 岁，n  = 7，n  = 6 白种人和n = 1 名非裔美国人）。RT 增加 了老年男性的全身瘦肉组织质量 ( p  = .017)、VL 厚度 ( p  = .012) 和膝关节伸肌扭矩 ( p = .029)。RT 也影响 mtDNA 甲基化组，因为 63% (159/254) 的 CpG 位点表现出甲基化降低 ( p  < .05)。与年轻男性相比，几个 mtDNA 位点在 RT 后在老年男性中呈现出更“年轻”的特征。调节复制和转录的 1.12 kb mtDNA D 环/控制区在 RT 后在老年男性中具有丰富的低甲基化。还观察到线粒体 H 和 L 链基因和复合 III/IV 蛋白水平的增强表达（p < .05）。虽然仅限于短期干预，但这是第一个表明 RT 改变骨骼肌中 mtDNA 甲基化组的证据。观察到的甲基化组改变可能会增强线粒体转录，而 RT 唤起线粒体甲基化组谱来模拟年轻男性。需要阐明这些发现相对于更广泛的 RT 诱导的表观遗传变化的重要性。