RNA-Sequencing Muscle Plasticity to Resistance Exercise Training and Disuse in Youth and Older Age

Abstract

Maintenance of skeletal muscle mass and function is critical to health and wellbeing throughout the lifespan. However, disuse through reduced physical activity (e.g., sedentarism), immobilisation, bed rest or microgravity has significant adverse effects on skeletal muscle health. Conversely, resistance exercise training (RET) induces positive muscle mass and strength adaptations. Several studies have employed microarray technology to understand the transcriptional basis of muscle atrophy and hypertrophy after disuse and RET, respectively, to devise fully effective therapeutic interventions. More recently, rapidly falling costs have seen RNA-sequencing (RNA-seq) increasingly applied in exploring muscle adaptations to RET and disuse. The aim of this review is to summarise the transcriptional responses to RET or disuse measured via RNA-seq in young and older adults. We also highlight analytical considerations to maximise the utility of RNA-seq in the context of skeletal muscle research. The limited number of muscle transcriptional signatures obtained thus far with RNA-seq are generally consistent with those obtained with microarrays. However, RNA-seq may provide additional molecular insight, particularly when combined with data-driven approaches such as correlation network analyses. In this context, it is essential to consider the most appropriate study design parameters as well as bioinformatic and statistical approaches. This will facilitate the use of RNA-seq to better understand the transcriptional regulators of skeletal muscle plasticity in response to increased or decreased use.