Multidimensional biocircuitry of exercise adaptation: integrating in vivo and ex vivo phenomics with miRNA mapping

In a randomized, dose-response trial, we used molecular and phenomic profiling to compare responses to traditional (TRAD) moderate intensity endurance and resistance training vs. high-intensity tactical training (HITT) that encompassed explosive whole-body interval training and high-intensity resistance training. Ninety-four participants (18-27 years) completed 12 weeks of TRAD or HITT followed by 4 weeks of detraining. Although similar performance and body composition improvements were observed in response to HITT and TRAD, some dose-dependent differences were observed for: (i) ex vivo muscle tissue changes in myofiber size, capillarization, satellite cell frequency, and mitochondrial function; and (ii) differential gene expression (DGE) of muscle and serum exosomal miRNAs (miRs). However, these dose-dependent ex vivo muscle adaptations were overshadowed by wide-ranging inter-individual response heterogeneity (IRH). We therefore explored IRH by first establishing minimum clinically important difference (MCID) scores to classify each participant based on MCIDs for functional muscle quality (fMQ) and cardiorespiratory fitness (CRF), and then modeling all data based on MCID classification. Using higher-order singular value decomposition (HOSVD), we established multidimensional biocircuitry linked to IRH that identified the most influential features across lifestyle, body composition, performance, ex vivo muscle tissue, and miRNA mapping domains. Via cross-comparison of MCID-linked miRs identified via DGE and HOSVD, nine miRs emerged as robust features of training adaptability, providing new insights into the integrated biocircuitry driving IRH.