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Novel Transcriptomic Predictors of Exercise Training‐Induced VO 2 max Improvements
Author(s) -
Smith Meghan,
Freeberg Kaitlin,
Craighead Daniel,
Bryan Angela,
Seals Douglas,
LaRocca Thomas
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.05283
Subject(s) - transcriptome , aerobic exercise , vo2 max , cardiorespiratory fitness , medicine , aerobic capacity , physical therapy , gene expression , gene , biology , genetics , heart rate , blood pressure
Aerobic exercise is universally recommended for reducing chronic disease risk, and maximal aerobic exercise capacity (VO 2 max) is one of the strongest predictors of healthspan and lifespan. However, VO 2 maximprovements 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 VO 2 max trainability, accessible transcriptomic predictors of this response have not been elucidated. Therefore, we determined if circulating transcriptomic predictors of VO 2 max 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 VO 2 max; and 2) change in a dose‐dependent fashion with exercise volume/intensity. We first identified 15 subjects with robust VO 2 max improvements (ΔVO 2 max 19 ± 1.2%) and 15 with minimal improvements (ΔVO 2 max 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 VO 2 max 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 VO 2 max improvements, we found greater levels of ~1800 genes/transcripts and lower levels of ~2900 transcripts before training (vs. subjects with minimal VO 2 max improvements). Enriched biological processes (gene ontology terms) in VO 2 max 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 VO 2 max response to aerobic exercise training using whole blood‐based transcriptomics/RNA‐seq approaches.