As we age, our bodies undergo gradual changes that affect muscles, metabolism, blood vessels, and the immune system. Scientists are increasingly interested in finding measurable biological markers that reflect these changes more accurately than chronological age alone.
Researchers at the University of the Balearic Islands, Spain examined extracellular vesicles in blood plasma from healthy individuals across different age groups. Extracellular vesicles, sometimes called exosomes, are tiny membrane-bound particles released by cells that carry proteins, lipids, and RNA molecules. Because they circulate in the bloodstream, they offer a minimally invasive way to monitor what is happening inside tissues throughout the body.
The team isolated plasma-derived extracellular vesicles using size exclusion chromatography and analyzed them using nanoparticle tracking, surface protein profiling, and small RNA sequencing. Interestingly, the overall size and number of vesicles did not change significantly with age. However, their molecular contents and surface characteristics did.
sRNA profile of plasma-derived EV
A Classification of EV-associated small RNAs by biotype. Bar chart showing the average read counts (log scale) of different small RNA biotypes identified in plasma-derived EVs. Annotation followed a hierarchical structure: known miRNA > novel miRNA > rRNA > tRNA > snRNA > snoRNA > repeat > exon > intron > other. While miRNAs were among the most abundant annotated classes, a considerable fraction of reads mapped to non-coding elements such as repeats, intronic/exonic regions, and an unclassified “other” category. B Cluster analysis of the differences between miRNA expressions. Colored boxes on the left indicate distinct microRNA clusters with differential expression patterns across age groups. The overall result of the (transcript per million) TPM cluster analysis is grouped by the log10(TPM + 1) value. The color scale from red to blue represents the level of miRNA expression. C, D, E Volcano diagrams comparing the miRNA expression between the old versus the young group (C), the old versus the middle-age groups (D) and the middle-age versus the young groups (E). The x-axis shows the fold-change (FC) in miRNA expression between different samples, and the y-axis shows the statistical significance of the differences between groups. Differentially expressed miRNAs are considered to be those with log2FC > 1 and p-value < 0.05. F Venn diagrams illustrating the overlap and uniqueness of significantly dysregulated miRNAs (FDR < 0.05) across pairwise age group comparisons (young vs. middle-aged; young vs. old; middle-aged vs. old), stratified by sex. Numbers indicate the count of unique and shared differentially expressed miRNAs.
Older individuals showed shifts in extracellular vesicle surface markers consistent with immunosenescence, the gradual aging of the immune system. More strikingly, the researchers identified distinct microRNA patterns associated with aging. Several microRNAs linked to muscle function, metabolism, and vascular health, including miR-206, miR-143-3p, miR-122-5p, and miR-20b-3p, were enriched in older participants. Another microRNA, miR-6529-5p, which has been associated with neuroprotection, was also elevated with age.
Further analysis of predicted gene targets revealed connections to well-known aging-related pathways such as Ras, VEGF, and MAPK signaling. In addition, specific extracellular vesicle microRNAs and particle counts correlated with biological aging markers, including GDF-15 levels, visceral fat accumulation, and muscle quality.
Together, these findings suggest that extracellular vesicles carry coordinated molecular signals that reflect musculoskeletal and metabolic aging. Because they can be obtained from a simple blood sample, plasma extracellular vesicles may serve as practical biomarkers to monitor biological aging and functional decline over time.
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