Molecular drivers of intercellular communication in physical exercise: insights from omics approaches

Physical activity enhances overall health by promoting coordinated communication among organs. Extracellular vesicles (EVs) play a key role in this process by transporting proteins, RNAs, lipids and other molecules that reflect how different tissues respond to physiological stress. Proteomics has been instrumental in clarifying how exercise reshapes EVs, providing insights into their role in mediating intercellular communication and systemic adaptations.

Current proteomics of exercise-induced EV remodeling are overviewed and integrated with complementary transcriptomic and lipidomic findings. We highlight modality-dependent changes in EV abundance and cargo, including antioxidant enzymes, metabolic regulators and muscle-associated markers, such as α-sarcoglycan. Methodological challenges in EV isolation, molecular profiling, data normalization, and functional validation are critically examined, along with the potential of EVs as minimally invasive sources of biomarkers and therapeutic vectors.

Circulating EVs transmit information between tissues to support the body's adaptation to exercise. Proteomics has identified important molecular signatures in EVs, but significant gaps remain regarding their cellular origin, the influence of exercise modalities on cargo selection, and the functional roles of these vesicles. Progress will require standardized workflows and integrated multi-omics approaches, combined with functional assays and physiological parameters of exercise adaptation.