Li Qiaowei, Liu Qin, Lin Zhong, Lin Wenwen, Huang Feng, Zhu Pengli
Shengli Clinical Medical College of Fujian Medical University, Fuzhou, 350001, P. R. China.
Fujian Provincial Institute of Clinical Geriatrics, Fujian Provincial Hospital, Fuzhou, 350001, P. R. China.
Open Life Sci. 2024 Sep 10;19(1):20220959. doi: 10.1515/biol-2022-0959. eCollection 2024.
Exercise training can significantly improve skeletal muscle mitochondrial function and has been proven to be highly relevant to alterations in skeletal muscle DNA methylation. However, it remains unclear whether late-in-life exercise has an effect on promoter methylation of PGC-1α, a key regulator of mitochondrial biogenesis. Here we employed two distinct exercise modalities, constant medium intensity exercise training (CMIT) and high-intensity interval exercise training (HIIT), to investigate their impacts on PGC-1α expression and methylation regulation in skeletal muscle of aged mice. The results revealed a notable decrease in PGC-1α expression in skeletal muscle of aged mice, accompanied by elevated methylation levels of the PGC-1α promoter, and increased DNA methyltransferase (DNMT) protein expressions. However, both forms of exercise training significantly corrected PGC-1α epigenetic changes, increased PGC-1α expression, and ameliorated skeletal muscle reduction. Furthermore, exercise training led to elevated expression of proteins related to mitochondrial biogenesis and energy metabolism in skeletal muscle, improving mitochondrial structure and function. In conclusion, late-in-life exercise improved skeletal muscle function, morphology, and mitochondria biogenesis, which may be associated with hypomethylation in promoters of PGC-1α and increased content of skeletal muscle PGC-1α. Notably, there was no clear difference between HIIT and CMIT in PGC-1α expression and skeletal muscle function.
运动训练可以显著改善骨骼肌线粒体功能，并且已被证明与骨骼肌DNA甲基化的改变高度相关。然而，目前尚不清楚晚年运动是否会对线粒体生物发生的关键调节因子PGC-1α的启动子甲基化产生影响。在此，我们采用两种不同的运动方式，即持续中等强度运动训练（CMIT）和高强度间歇运动训练（HIIT），来研究它们对衰老小鼠骨骼肌中PGC-1α表达和甲基化调控的影响。结果显示，衰老小鼠骨骼肌中PGC-1α表达显著降低，同时PGC-1α启动子的甲基化水平升高，且DNA甲基转移酶（DNMT）蛋白表达增加。然而，两种形式的运动训练均显著纠正了PGC-1α的表观遗传变化，增加了PGC-1α表达，并改善了骨骼肌萎缩。此外，运动训练导致骨骼肌中与线粒体生物发生和能量代谢相关的蛋白质表达升高，改善了线粒体的结构和功能。总之，晚年运动改善了骨骼肌功能、形态以及线粒体生物发生，这可能与PGC-1α启动子低甲基化和骨骼肌PGC-1α含量增加有关。值得注意的是，HIIT和CMIT在PGC-1α表达和骨骼肌功能方面没有明显差异。
