Yamamoto Keisuke, Chiba Mitsuru
Department of Bioscience and Laboratory Medicine, Graduate School of Health Sciences, Hirosaki University, Hirosaki, Aomori 036-8564, Japan.
Research Center for Biomedical Sciences, Hirosaki University, Hirosaki, Aomori 036-8564, Japan.
Exp Ther Med. 2024 Nov 25;29(2):22. doi: 10.3892/etm.2024.12772. eCollection 2025 Feb.
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.
近年来，日本人口老龄化，患各种与年龄相关疾病的风险增加。因此，有必要分析衰老的特征成分，并研究它们与疾病的关联，以便在早期阶段检测出与年龄相关的疾病。在本研究中，分析了82 - 102周龄小鼠血清细胞外囊泡（EVs）中的微小RNA（miRNAs/miRs），以鉴定衰老特征性的miRNAs。观察到mmu-miR-21a-5p的表达增加。这些miRNAs可能来源于衰老的血管内皮细胞，对4 Gy辐射诱导衰老的人脐静脉内皮细胞（HUVECs）的RNA测序数据（GSE130727）显示，这些miRNAs参与细胞周期和DNA修复。还鉴定了与衰老相关途径的注释。证实了miR-21-5p靶基因在人和小鼠中具有相同序列，其表达降低。在类似条件下诱导衰老的HUVECs中，观察到衰老相关β-半乳糖苷酶活性增加和细胞内miR-21-5p表达增加。一部分miR-21-5p通过内化四跨膜蛋白阳性的EVs分泌到细胞外，miR-21-5p被分泌到细胞外空间。本研究还表明，在血管内皮细胞衰老过程中，miR-21-5p表达上调，miR-21-5p的细胞外分泌增强。这些发现表明，血清miR-21-5p升高代表血管内皮细胞衰老的生物标志物。
