Long non-coding RNAs in exercise: the hidden regulators of adaptation

Area of Science:

• Molecular Biology
• Exercise Physiology
• Genomics

Background:

• Regular physical activity induces molecular adaptations in multiple organ systems, enhancing performance and cardiometabolic health.
• Classical signaling pathways (AMPK-PGC‑1α, Ca²⁺/calcineurin, mTORC1) are well-studied, but the role of long non-coding RNAs (lncRNAs) in exercise adaptation is emerging.
• lncRNAs are increasingly recognized as key regulators of exercise-induced cellular and tissue remodeling.

Purpose of the Study:

• To synthesize current evidence on the role of lncRNAs as molecular mediators of exercise-induced adaptations.
• To highlight specific lncRNAs involved in skeletal muscle, cardiac, and neural responses to exercise.
• To discuss the potential of lncRNAs as biomarkers for training adaptation and vascular function.

Main Methods:

• Review of mechanistic studies on lncRNA function during exercise.
• Analysis of systems-level transcriptomics data from human training studies.
• Examination of emerging clinical data on circulating lncRNAs.

Main Results:

• Exercise-induced lncRNAs (e.g., CYTOR, TUG1) modulate skeletal muscle function, including myogenesis and mitochondrial activity.
• Cardiac lncRNAs (e.g., CPhar, lncExACT1, Mhrt779) differentiate physiological from pathological hypertrophy and confer "memory" of antihypertrophic effects.
• Endothelial NEAT1 links aerobic training to atheroprotection via m⁶A-modulated pyroptosis, while MALAT1 mediates neuroprotection.
• Omics analyses reveal tissue- and cell-type-specific lncRNA programs during human training.
• Circulating lncRNAs (e.g., MALAT1, HOTTIP) show potential as biomarkers for vascular function and training adaptation.

Conclusions:

• lncRNAs represent a critical regulatory layer governing the quality, magnitude, and persistence of exercise adaptations.
• Current mechanistic understanding is limited to a few key lncRNAs, with under-exploration in non-muscle tissues and inter-organ communication.
• Future research should focus on functional validation of identified lncRNAs, dissecting exerkines, and integrating lncRNA biology into precision exercise medicine.