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干细胞衍生的细胞外 microRNAs 在与年龄相关的人类疾病和不同的长寿疗法中的新兴作用。

Emerging role of stem cell-derived extracellular microRNAs in age-associated human diseases and in different therapies of longevity.

机构信息

Interventional Regenerative Medicine and Imaging Laboratory, Department of Radiology, Stanford University, Palo Alto, California, 94304, USA.

Interventional Regenerative Medicine and Imaging Laboratory, Department of Radiology, Stanford University, Palo Alto, California, 94304, USA.

出版信息

Ageing Res Rev. 2020 Jan;57:100979. doi: 10.1016/j.arr.2019.100979. Epub 2019 Nov 5.

Abstract

Organismal aging involves the progressive decline in organ function and increased susceptibility to age-associated diseases. This has been associated with the aging of stem cell populations within the body that decreases the capacity of stem cells to self-renew, differentiate, and regenerate damaged tissues and organs. This review aims to explore how aging is associated with the dysregulation of stem cell-derived extracellular vesicles (SCEVs) and their corresponding miRNA cargo (SCEV-miRNAs), which are short non-coding RNAs involved in post-transcriptional regulation of target genes. Recent evidence has suggested that in aging stem cells, SCEV-miRNAs may play a vital role regulating various processes that contribute to aging: cellular senescence, stem cell exhaustion, telomere length, and circadian rhythm. Hence, further clarifying the age-dependent molecular mechanisms through which SCEV-miRNAs exert their downstream effects may inform a greater understanding of the biology of aging, elucidate their role in stem cell function, and identify important targets for future regenerative therapies. Additionally, current studies evaluating therapeutic role of SCEVs and SCEV-miRNAs in treating several age-associated diseases are also discussed.

摘要

生物体的衰老涉及器官功能的逐渐衰退和对与年龄相关疾病的易感性增加。这与体内干细胞群体的衰老有关,干细胞群体的衰老降低了干细胞自我更新、分化和再生受损组织和器官的能力。本综述旨在探讨衰老与干细胞衍生的细胞外囊泡(SCEV)及其相应的 miRNA 货物(SCEV-miRNAs)的失调之间的关系,SCEV-miRNAs 是参与靶基因转录后调控的短非编码 RNA。最近的证据表明,在衰老的干细胞中,SCEV-miRNAs 可能在调节各种与衰老有关的过程中发挥重要作用:细胞衰老、干细胞衰竭、端粒长度和昼夜节律。因此,进一步阐明 SCEV-miRNAs 发挥其下游效应的依赖年龄的分子机制,可以更好地了解衰老的生物学,阐明它们在干细胞功能中的作用,并确定未来再生疗法的重要靶点。此外,还讨论了目前评估 SCEV 和 SCEV-miRNAs 在治疗几种与年龄相关疾病中的治疗作用的研究。

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