Summary

MicroRNAs (miRNAs) are pivotal post-transcriptional regulators that fine-tune gene expression in response to physiological stress. In the context of exercise, both intracellular and circulating miRNAs orchestrate the adaptive responses of skeletal muscle, cardiovascular tissue and distant organs. Exercise-induced changes in miRNA expression influence mitochondrial biogenesis, muscle remodelling, angiogenesis and tissue repair. Moreover, secreted miRNAs within extracellular vesicles or bound to protein complexes mediate inter-tissue communication, conveying molecular signals from contracting muscle to the brain, heart and immune system. Profiling of circulating miRNAs has revealed dynamic signatures that correlate with exercise intensity, training status and performance capacity, positioning miRNAs as promising biomarkers for monitoring adaptation and recovery. Standardisation of sampling and analytical protocols remains critical to ensure reproducibility across studies. Ultimately, a detailed understanding of miRNA networks in exercise physiology may translate into targeted therapies for metabolic disorders, cardiovascular disease and age-related decline.

Research from Nature Portfolio

Recent work has addressed the challenge of technical variability in circulating miRNA studies by comparing multiple RT-qPCR normalisation approaches in sedentary and highly trained individuals. This analysis identified a single reference miRNA that minimises technical noise and highlights genuine differences in skeletal muscle- and bone-associated circulating miRNA profiles between cohorts. By establishing a robust and reproducible normalisation strategy, this study lays the groundwork for reliable inter-study comparisons and the future clinical application of circulating miRNAs as biomarkers of training status.

MicroRNA Regulation in Exercise Physiology publication trend

The graph below shows the total number of articles in microrna regulation in exercise physiology across all publications each year (not limited to Nature Index journals).

Technical terms

microRNA (miRNA): Small non-coding RNA (~22 nucleotides) that binds messenger RNA to inhibit translation or promote degradation.

Circulating microRNA (c-miRNA): Extracellular miRNA species detected in body fluids, reflecting tissue-specific expression and secretory pathways.

Extracellular vesicle (EV): Lipid-enclosed particle secreted by cells, transporting proteins, lipids and nucleic acids including miRNAs between cells.

RT-qPCR normalisation: Use of stable reference molecules to correct for technical variation in quantitative PCR assays.

References

  1. Normalization strategies differently affect circulating miRNA profile associated with the training status. Scientific Reports (2019).
  2. Muscle‐Derived Small Extracellular Vesicles Mediate Exercise‐Induced Cognitive Protection in Chronic Cerebral Hypoperfusion. Advanced Science (2025).
  3. miR-17-3p Contributes to Exercise-Induced Cardiac Growth and Protects against Myocardial Ischemia-Reperfusion Injury. Theranostics (2017).
  4. The miRNA Plasma Signature in Response to Acute Aerobic Exercise and Endurance Training. PLOS ONE (2014).
  5. Circulating MicroRNAs as Potential Biomarkers of Exercise Response. International Journal of Molecular Sciences (2016).
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