MicroRNA‑21‑5p expression in extracellular vesicles is increased in the blood of aging mice and in vascular endothelial cells induced by ionizing radiation

In recent years, the Japanese population has been aging and the risk of contracting various age-related diseases has increased. Thus, there is a need to analyze components that are characteristic of aging and examine their association with diseases to detect age-related diseases at an early stage. In the present study, microRNAs (miRNAs/miRs) in serum extracellular vesicles (EVs) of 82-102-week-old mice were analyzed to identify miRNAs characteristic of aging. Increased expression of mmu-miR-21a-5p was observed. These miRNAs may be derived from senescent vascular endothelial cells, and RNA-sequencing data (GSE130727) of HUVECs induced to senesce by 4 Gy of radiation revealed that the miRNAs were involved in the cell cycle and DNA repair. Annotations to senescence-related pathways were also identified. Reduced expression of the miR-21-5p target gene, which has an identical sequence in humans and mice, was confirmed. In HUVECs induced to age under similar conditions, increased senescence-associated β-galactosidase activity and increased intracellular miR-21-5p expression were observed. A portion of the miR-21-5p was secreted extracellularly by internalizing tetraspanin-positive EVs, and miR-21-5p was secreted into the extracellular space. The present study also demonstrated that miR-21-5p expression was upregulated and extracellular secretion of miR-21-5p was enhanced during vascular endothelial cell senescence. These findings suggested that increased serum miR-21-5p represents a biomarker for vascular endothelial cell senescence.