MicroRNA profiles in plasma-derived extracellular vesicles across the human lifespan.
Abstract
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.
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Research summary
The study identifies distinct microRNA signatures in extracellular vesicles that correlate with biological aging markers, suggesting their potential as biomarkers for aging and functional decline. The research addresses physiological changes during aging and explores biomarkers that could reflect the underlying mechanisms of aging, which is pertinent to longevity research.
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