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.
Data availability
The datasets generated and/or analyzed during the current study are not publicly available due to ethical restrictions related to patient privacy and confidentiality, but are available from the corresponding author on reasonable request. Data are located in controlled access data storage at Health Research Institute of the Balearic Islands (IdISBa).
Code availability
All scripts used for the analysis (preprocessing, differential expression, EV-miRNA quantification, and statistical modeling) are available upon reasonable request from the corresponding author.
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Acknowledgements
This work was supported by the Instituto de Salud Carlos III (ISCIII) (Miguel Servet Program-MS19/00201, and PI21/01480), Ministerio de Ciencia, Innovación y Universidades (Agencia Española de Investigación (AEI), CNS2022-135110), and the Impost turisme sostenible/Govern de les Illes Balears (FOLIUM program—19/01 and SYNERGIA program SYN22/04). We gratefully acknowledge the essential contributions of the Clinical Unit of the Research Institute of the Balearic Islands, the Biobank Unit, and the Hospital Universitario Son Espases for their support in data collection. We are especially thankful to all the participants who generously contributed to this study. We also acknowledge Novogene (UK) Company Limited for their sequencing services. We would like to thank Anna Estela Bolta, PhD, Senior Account Manager (Novogene, UK), for her support and assistance throughout the project.
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C.R.-M., J.M.R., M.M., X.C., M.T.-M., C.N.-E., and M.G.-F. were involved in the study conception, design, and experimental protocol; C.R.-M., J.M.R., X.C., A.M.G.-P., C.N.-E., L.M., M.T.-M., A.S.P., A.M.-L., M.M.-C., A.B.-A., J.M.R., and M.G.-F. collected the data and helped with the data analysis. C.R.-M., C.N.-E., M.T.-M., X.C., J.M.R., and M.G.-F. analyzed the data and wrote the manuscript. All authors have read and agreed to the published version of the manuscript.
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Ráez-Meseguer, C., Navas-Enamorado, C., Capó, X. et al. MicroRNA profiles in plasma-derived extracellular vesicles across the human lifespan. npj Aging (2026). https://doi.org/10.1038/s41514-025-00321-1
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DOI: https://doi.org/10.1038/s41514-025-00321-1
