Genome-wide DNA Methylation and Transcriptome-wide Responses to a Bout of Higher- Versus Lower-load Resistance Training in Previously Trained Men

Abstract

We sought to determine how genome-wide DNA methylation and transcriptome responses in skeletal muscle differed between one bout of lower-load versus higher-load resistance exercise. Previously trained college-aged males (n=11, age: 23±4 years old, percent body fat: 11.4 ± 6.4%, training experience: 4 ± 3 years, squat strength relative to body weight: 1.7 ± 0.3) performed two bouts of resistance exercise separated by one week. The higher-load bout consisted of 4 sets of back squats and 4 sets of leg extensions to failure using 80% of their estimated one-repetition maximum (Est. 1-RM) (80 Fail), whereas the lower-load bout consisted of this same paradigm using 30% of their Est. 1-RM (30 Fail). Vastus lateralis muscle biopsies were collected before (PRE), 3 hours (3hPOST), and 6 hours (6hrPOST) after each exercise bout. DNA and RNA were batch-isolated from muscle tissue and analyzed for genome-wide DNA methylation and mRNA expression, respectively, using the 850k Illumina MethylationEPIC array and Clariom S mRNA array. The total number of repetitions performed were significantly greater during the 30 Fail versus 80 Fail bout (p<0.001); however, total training volume (sets x reps x load) was not significantly different between conditions (p=0.571). While 30 Fail training generally led to greater hypomethylation across various promoter regions, the transcriptome-wide responses between bouts were largely similar. Both bouts altered mRNAs involved in inflammatory signaling (e.g., Toll receptor signaling, CCKR signaling, chemokine and cytokine signaling), apoptosis signaling, gonadotropin-releasing hormone signaling, and integrin signaling. Although several studies have examined the muscle-molecular responses to higher- versus lower-load resistance training, this is the first multi-omics comparison of these paradigms. Our transcriptomic data suggest that the molecular signaling events during the early post-exercise period are largely similar, and this may explain why similar longer-term phenotypes (e.g., myofiber hypertrophy) result from these two resistance training-to-failure modalities.