Total Transcriptome Responses to Low and Higher Intensity Aerobic Exercise Interventions in Older Adults

Aerobic exercise is a universally recommended strategy for increasing healthspan, and recent advances in next-generation sequencing and bioinformatics (e.g., RNA-seq/transcriptomics) have made it possible to broadly profile the molecular transducers of exercise. However, most transcriptome studies of exercise have focused on coding genes only, and the transcriptomic response to different exercise interventions has not been characterized by RNA-seq in older adults. Therefore, we performed total RNA-seq (to capture both coding and non-coding gene expression) on peripheral blood mononuclear cells collected from healthy, previously sedentary older adults (males and females, aged 70 ± 1 years). Samples were collected before and after 16 weeks of either low-intensity continuous training (LICT, 50% maximum heart rate, 3 x 30 min/week) or moderate-intensity continuous training plus interval training (MICT+IT, 60-80% maximum heart rate, progressively increased to include IT, 3 x 30 min/week). We found that both interventions modified biological processes (transcriptome modules) related to oxygen transport and reduced inflammatory signaling/immune activation processes (more pronounced with LICT). Interestingly, transcriptome changes unique to LICT subjects included increased expression of genes linked with vascularization and endothelial cell migration, whereas MICT+IT was uniquely associated with a robust increase in antioxidant response gene expression. We also observed numerous changes in long non-coding RNAs and microRNAs that could be linked with these exercise-associated gene expression changes with both interventions. These data provide a first comprehensive look into transcriptomic changes associated with moderate vs. low intensity aerobic exercise in older adults, and they suggest distinct benefits of each exercise strategy.