Effects of different types of resistance exercise failure training on the methylation status of genes that drive skeletal muscle hypertrophy

OBJECTIVE: We sought to determine how one bout of resistance training to failure with either higher repetitions (30FAIL) or lower repetitions (80FAIL) affected the promoter methylation statuses of genes that drive skeletal muscle hypertrophy. HYPOTHESES: We hypothesized that a bout of 80FAIL training would lead to a more robust hypomethylation of genes that regulate skeletal muscle hypertrophy compared to 30FAIL training. METHODS: Eleven previously-trained college-aged men (age: 23 ± 4 years, 11.42 ± 6.38 percent fat, 4 ± 3 years training experience) volunteered for this study. Each participant underwent two training bouts (spaced one week apart) involving either: i) 30FAIL training; 4 sets of back squats and 4 sets of leg extensors to failure at 30% of one-repetition maximum (1RM), or: ii) 80FAIL training; 4 sets of both exercises at 80% of 1RM. Muscle biopsies from the vastus lateralis were collected prior to each bout (PRE), 3 hours following each bout (3hPOST), and 6 hours following each bout (6hPOST). Following the conclusion of the study, tissue was batch-processed for DNA isolation, and DNA was subjected to the Illumina MethylationEPIC array. In an a priori fashion, genes that have been shown to induce skeletal muscle hypertrophy in genetic mouse models were the target of this investigation (Verbrugge et al. Frontiers Physiol, 2019). RESULTS: Total training volume (sets x reps x load) between the 30FAIL and 80FAIL bouts were not significantly different (p= 0.571). Differentially methylated region changes for the following genes from PRE to 3hPOST and PRE to 6hPOST are presented herein: SKI, FST, AKT1, ACVR2B, MSTN, KLF10, RHEB, IGF1, PAPPA, PPARD, IKBKB, FSTL3, ATGR1, UCN3, MCU, JUNB, NCOR1, GPRASP1, GRB10, MMP9, DGKZ, PPARGC1A, SMAD4, LTBP4, BMPR1A, CRTC2, XIAP, DGAT1, THRA, ADRB2, ASB15, CAST, EIF2B5, BDKRB2, TPT1, NR3C1, NR4A1, GNAS, PLD1, CRYM, CAMKK1, YAP1, INHBA, TP53INP2, INHBB, NOL3, and ESR1. Additionally, significant differences between conditions at each time point are highlighted. CONCLUSIONS: This study continues to display how different modalities of resistance training affect the skeletal muscle molecular milieu and furthers our scientific understanding of factors that contribute to training adaptations. © FASEB.