Novel Transcriptomic Predictors of Exercise Training‐Induced VO 2 max Improvements

Abstract

Listen

Translate article

Aerobic exercise is universally recommended for reducing chronic disease risk, and maximal aerobic exercise capacity (VO2max) is one of the strongest predictors of healthspan and lifespan. However, VO2maximprovements in response to exercise training vary remarkably between individuals. The mechanisms driving this variability are heavily studied, but while genome-wide association studies have estimated the heritability of VO2max trainability, accessible transcriptomic predictors of this response have not been elucidated. Therefore, we determined if circulating transcriptomic predictors of VO2max trainability could be identified by studying gene expression signatures that: 1) differ between individuals who respond to aerobic exercise training with robust vs. little/no increases in VO2max; and 2) change in a dose-dependent fashion with exercise volume/intensity. We first identified 15 subjects with robust VO2max improvements (ΔVO2max 19 ± 1.2%) and 15 with minimal improvements (ΔVO2max 0 ± 1.0%) in a 16-week trial consisting of four supervised aerobic exercise training interventions (permutations of high/low volume and high/low intensity). Then, we performed total transcriptomics (RNA-seq) on blood samples (PaxGene RNA tubes) collected before and after the interventions, as well as gene ontology analyses to identify differences in biological processes associated with exercise and VO2max responses. All subjects were healthy, sedentary women aged 38 ± 0.9 years, and at baseline were phenotypically similar (i.e., no differences in basic clinical variables). However, in subjects with robust VO2max improvements, we found greater levels of ~1800 genes/transcripts and lower levels of ~2900 transcripts before training (vs. subjects with minimal VO2max improvements). Enriched biological processes (gene ontology terms) in VO2max responders at baseline included inflammatory signaling and other adverse pathways, while reduced signatures were related to metabolism/mitochondrial function. Strikingly, these baseline gene expression differences were normalized by exercise interventions in a dose-dependent manner in the entire group (i.e., most normalized by high volume/high intensity exercise and least normalized by low volume/low intensity exercise). These data suggest it may be possible to predict the VO2max response to aerobic exercise training using whole blood-based transcriptomics/RNA-seq approaches.