Extracellular Vesicles as Communicators of Senescence in Musculoskeletal Aging.
Extracellular Vesicles as Communicators of Senescence in Musculoskeletal Aging.
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DOI：
10.1002/jbm4.10686
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发表时间：
2022-11
期刊：
影响因子：
3.8
通讯作者：
Hamrick, Mark W
中科院分区：
文献类型：
--
作者：
Alfonzo, Monica Correa;Al Saedi, Ahmed;Fulzele, Sadanand;Hamrick, Mark W
细胞外囊泡（EVs），包括外泌体和微囊泡，由许多细胞类型释放。目前认为，EVs在健康衰老和年龄相关疾病的细胞间通讯中起着关键作用。最近的研究表明，衰老是衰老的一个关键标志，它会增加EVs的分泌。此外，电动汽车可以运输蛋白质和microrna (mirna)，这是衰老相关分泌表型（SASP）的关键组成部分。在这里，我们回顾了SASP相关的mirna与衰老的肌肉骨骼变性有关的证据。具体来说，衰老相关的mirna在骨骼肌细胞和纤维脂肪祖细胞释放的ev中分别升高，这些细胞分别伴随着衰老和废用性萎缩。在骨关节炎患者滑液中的ev中检测到许多相同的衰老相关mirna，这些mirna可促进软骨变性。最后，衰老相关的mirna由骨髓源性干细胞（基质）分泌，影响邻近的造血干细胞并在血液中循环。衰老相关的miRNA mir - 34a，已知靶向Wnt和Notch通路以及细胞存活因子Sirt1和Bcl2，在患有肌肉萎缩、骨质丢失和骨关节炎的人和动物的EVs中检测到。这些发现表明，抑制EV衍生的衰老相关mirna（如miR - 34a）的分泌，或增加内源性长链非编码rna（如抑制miR - 34a的MALAT1）的竞争水平，可能有助于改善衰老时的肌肉骨骼功能。©2022作者。JBMR Plus由Wiley期刊有限责任公司代表美国骨骼和矿物研究协会出版。衰老细胞比健康细胞分泌更多的细胞外囊泡（EVs）。由衰老的肌肉、骨骼和软骨细胞释放的ev携带与衰老相关的microrna，可以诱导邻近细胞衰老，驱动组织变性。
Extracellular vesicles (EVs), including exosomes and microvesicles, are released by numerous cell types. EVs are now acknowledged as playing a critical role in cell–cell communication in healthy aging as well as in age‐related diseases. Recently it was shown that senescence, a key hallmark of aging, increases the secretion of EVs. Moreover, EVs can transport proteins and microRNAs (miRNAs) that are key components of the senescence‐associated secretory phenotype (SASP). Here we review evidence that SASP‐related miRNAs are involved in musculoskeletal degeneration with aging. Specifically, senescence‐related miRNAs are elevated in EVs released by skeletal muscle myocytes and fibro‐adipogenic progenitor cells with aging and disuse atrophy, respectively. Many of these same senescence‐related miRNAs are detected in EVs from the synovial fluid of patients with osteoarthritis, and these miRNAs can contribute to cartilage degeneration. Finally, senescence‐associated miRNAs are secreted from bone marrow–derived stem (stromal) cells impacting neighboring hematopoietic stem cells and circulating in the blood. The senescence‐associated miRNA mir‐34a, which is known to target Wnt and Notch pathways as well as the cell survival factors Sirt1 and Bcl2, is detected in EVs from human and animal subjects with muscle atrophy, bone loss, and osteoarthritis. These findings suggest that suppressing the secretion of EV‐derived, senescence‐related miRNAs, such as miR‐34a, or increasing levels of competing endogenous long noncoding RNAs, such as MALAT1 that inhibit miR‐34a, may help to improve musculoskeletal function with aging. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. Senescent cells secrete more extracellular vesicles (EVs) than healthy cells. EVs released by senescent muscle, bone, and cartilage cells carry senescence‐associated microRNAs that can induce senescence in neighboring cells, driving tissue degeneration.