(A) Schematic representation of experimental conditions and types of analysis undertaken across the time-course. The image of a muscle represents the time point for analysis of muscle mass via (i) DEXA and strength via (ii) isometric quadriceps muscle torque using an isokinetic dynamometer. The images of muscle tissue also represent the time point of skeletal muscle biopsy of the Vastus Lateralis, muscle sample preparation for downstream analysis of (iii) Infinium MethylationEPIC BeadChip arrays (850 K CpG sites) methylome wide array (iv) and rt-qRT-PCR for gene expression analysis of important genes identified following methylome wide analysis. (B) Weekly total volume of resistance exercise undertaken by human participants (n = 7) during the first 7-week resistance exercise period (loading, weeks 1–7), followed by a 7 week cessation of resistance exercise (unloading, weeks 8–14) and the later second period of 7 weeks resistance exercise (reloading, weeks 15–21). Data represents volume load as calculated by ((load (Kg) x reps) x sets)) averaged across 3 resistance exercise sessions per week. Data presented mean ± SEM. (Ci) Lean lower limb mass changes in human subjects (n = 7) after a period of 7 weeks resistance exercise (loading), exercise cessation (unloading) and a subsequent second period of 7 weeks resistance exercise (reloading). Total limb lean mass normalised to baseline (percentage change). Significant change compared to baseline represented by * and significant difference to all other conditions represented by ** (Cii) Total lean mass percentage change when loading is normalised to baseline, and reloading normalised to unloading to account for starting lean mass in both conditions. Pairwise t-test of significance indicated by *. All data presented as mean ± SEM (n = 7).