MicroRNA profiles in plasma-derived extracellular vesicles across the human lifespan

Extracellular vesicles (EVs) are key mediators of intercellular communication and may reflect physiological changes during aging. We analyzed plasma-derived EVs from a healthy aging cohort stratified by age, using size exclusion chromatography, surface profiling, nanoparticle tracking, and small RNA sequencing. While EV size and concentration remained largely unchanged, older individuals showed shifts in EV immunophenotype consistent with immunosenescence and displayed distinct miRNA signatures enriched in muscle-specific and metabolism-related miRNAs, including miR-206, miR-143-3p, miR-122-5p, and miR-20b-3p-linked to muscle, metabolic, and vascular function. Notably, miR-6529-5p, associated with neuroprotection, was elevated in aging. Target gene analysis revealed involvement in aging pathways such as Ras, VEGF, and MAPK signaling. EV miRNAs and particle counts correlated with biological aging markers, including GDF-15, visceral fat, and muscle quality. These findings highlight coordinated age-related changes in EVs reflecting musculoskeletal and metabolic aging and support their potential as minimally invasive biomarkers of biological aging and functional decline.