Skeletal Muscle Phenotype Is Augmented Through The Epigenomic Regulation Of Myogenic Transcription Factors

Abstract

PURPOSE: Recently, a training-retraining (TRT) paradigm in which 3 month old rodents underwent an initial cycle of SSC RTET followed by another bout at 6 months led to increases in isometric/dynamic peak force and muscle mass relative to naïve 6 month old rats, thus augmenting the trainability of muscle into adulthood. However, the molecular underpinnings of this response is unknown. Therefore, we sought to determine whether this TRT paradigm has positive effects on transcription factor (TF) methylation and expression in adult skeletal muscle. METHODS: F344xBN hybrid rats were SSC RTET on an in vivo dynamometer 3 days/week for 1 month at 3 months and again at 6 months of age (TRT), or just at 6 months (T). Gene expression and DNA methylation were quantified via PCR Arrays (Qiagen®). RESULTS: TRT group had 17 significantly differentially expressed genes (SDEGs) in the TF pathway, including Myf5; T expressed only 3 SDEGs. TRT had decreased TF methylation compared to T (4.1±0.01 vs. 2.6±0.01%; p<0.05). CONCLUSIONS: Adaptive benefits at adulthood following an initial SSC RTET stimulus are supported by altered TF methylation and gene expression. These results advocate RTET at early life to preserve muscle as one ages through an epigenomic muscle memory.