Age-Related Changes in Plasma Extracellular Vesicle Characteristics and Internalization by Leukocytes.
Age-Related Changes in Plasma Extracellular Vesicle Characteristics and Internalization by Leukocytes.
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DOI：
10.1038/s41598-017-01386-z
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发表时间：
2017-05-02
影响因子：
4.6
通讯作者：
Evans MK
中科院分区：
文献类型：
--
作者：
Eitan E;Green J;Bodogai M;Mode NA;Bæk R;Jørgensen MM;Freeman DW;Witwer KW;Zonderman AB;Biragyn A;Mattson MP;Noren Hooten N;Evans MK
细胞释放含有蛋白质、脂质和rna的脂质结合细胞外囊泡（EVs；外泌体、微囊泡和凋亡小体）进入循环。囊泡介导邻近细胞和远处细胞之间的细胞间通讯。人们对使用ev作为年龄相关疾病（包括癌症、神经退行性疾病、代谢和心血管疾病）的生物标志物非常感兴趣。大多数研究的重点是在比较疾病状态和匹配对照时确定ev的差异。在这里，我们通过横断面和纵向研究分析了循环血浆EVs，以解决社区居民中与年龄相关的变化。我们发现EV浓度随着年龄的增长而降低。此外，与来自年轻人的EVs相比，来自老年人的EVs更容易被B细胞内化，单核细胞上的MHC-II表达增加，这表明随着年龄的增长EVs浓度下降可能部分归因于内化增加。EV激活单核细胞和B细胞，LPS激活B细胞增强EV内化。我们还报告了个体受试者的EV浓度和蛋白量随时间的相对稳定性。我们的数据为建立ev与人类年龄的关系提供了重要信息，这将进一步有助于开发基于ev的衰老和年龄相关疾病诊断方法。
Cells release lipid-bound extracellular vesicles (EVs; exosomes, microvesicles and apoptotic bodies) containing proteins, lipids and RNAs into the circulation. Vesicles mediate intercellular communication between both neighboring and distant cells. There is substantial interest in using EVs as biomarkers for age-related diseases including cancer, and neurodegenerative, metabolic and cardiovascular diseases. The majority of research focuses on identifying differences in EVs when comparing disease states and matched controls. Here, we analyzed circulating plasma EVs in a cross-sectional and longitudinal study in order to address age-related changes in community-dwelling individuals. We found that EV concentration decreases with advancing age. Furthermore, EVs from older individuals were more readily internalized by B cells and increased MHC-II expression on monocytes compared with EVs from younger individuals, indicating that the decreased concentration of EVs with age may be due in part to increased internalization. EVs activated both monocytes and B cells, and activation of B cells by LPS enhanced EV internalization. We also report a relative stability of EV concentration and protein amount in individual subjects over time. Our data provide important information towards establishing a profile of EVs with human age, which will further aid in the development of EV-based diagnostics for aging and age-related diseases.