Multi-omic analysis of skeletal muscle in response to disuse and retraining in trained and untrained individuals

Abstract

We previously examined how resistance training status (RT) in young healthy individuals, either well-resistance trained (T) or untrained (UT), affected molecular markers with leg immobilization followed by recovery RT. Participants largely showed similar patterns at the molecular level despite divergent phenotypic patterns. Therefore, we opted to conduct the current study, where the transcriptome, microRNA (miR)-ome, and the proteome were examined at baseline (PRE), after two weeks of limb immobilization (MID) and after a subsequent eight weeks of RT (POST). Bioinformatic methods were used to analyze each -ome independently for multiple comparisons (training status at each timepoint, training status by timepoint, time alone), predict the top ten features predictive of disuse atrophy and RT-induced hypertrophy, and integrate each -ome to reveal modules affected from RNA to protein. The majority of identified differences were primarily time-driven rather than training status-driven, indicating a similar molecular response to each phase of this intervention regardless of training status. Furthermore, the proteome appeared to be the most responsive to both phases of this intervention. It was also revealed that different physiological systems were implicated with disuse atrophy at the transcriptome (mitochondrial and neuronal communication), miR-ome (ERBB signaling, cell cycle), and proteome (rRNA regulation, ubiquitin proteases), deepening the notion that atrophy is a multifactorial and complex phenomenon. Finally, the potentially novel ALK-STAT3 axis was revealed as a potential signaling node in disuse atrophy when all three -omes were integrated. These results are limited to a young adult cohort undergoing noncomplicated disuse atrophy followed by lower body focused RT.