Extracellular vesicles (EVs) are implicated in inter-organ communication, which becomes
particularly relevant during aging and exercise. DNA methylation-based aging clocks
reflect lifestyle and environmental factors, while regular exercise is known to induce
adaptive responses, including epigenetic adaptations. Twenty individuals with High-fitness
(aged 57.7 ± 9.8 years) and twenty Medium–Low-fitness (aged 57.5 ± 9.7 years) subjects
provided blood samples. EVs were isolated from the samples using a size exclusion
chromatography (SEC)-based method, and their protein content was analyzed by mass
spectrometry (MS). Acceleration of the biological age estimator DNAmFitAge (AgeAccelFit)
was associated with the protein cargo of EVs, whereas PhenoAge and GrimAge acceleration
did not show a significant relationship. This finding suggests that the epigenetic
aging-modulating role of exercise may involve inter-organ communication via EVs. Set
Enrichment Analysis was performed to identify enriched Gene Ontology (GO) terms for
sets of proteins that were either correlated with AgeAccelFit or detected exclusively
in individuals with high levels of aerobic fitness. The protein cargo of EVs further
suggests that inter-organ communication influences inflammation, the immune system,
cellular repair, adhesion, metabolism and coagulation. Our findings help to understand
the preventive role of exercise, which could be mediated in part by EVs.
