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微小RNA作为衰老及衰老相关疾病的外周生物标志物

MicroRNAs as Peripheral Biomarkers in Aging and Age-Related Diseases.

作者信息

Kumar S, Vijayan M, Bhatti J S, Reddy P H

机构信息

Garrison Institute on Aging, Texas Tech University Health Sciences Center, Lubbock, TX, United States.

Garrison Institute on Aging, Texas Tech University Health Sciences Center, Lubbock, TX, United States.

出版信息

Prog Mol Biol Transl Sci. 2017;146:47-94. doi: 10.1016/bs.pmbts.2016.12.013. Epub 2017 Feb 8.

Abstract

MicroRNAs (miRNAs) are found in the circulatory biofluids considering the important molecules for biomarker study in aging and age-related diseases. Blood or blood components (serum/plasma) are primary sources of circulatory miRNAs and can release these in cell-free form either bound with some protein components or encapsulated with microvesicle particles, called exosomes. miRNAs are quite stable in the peripheral circulation and can be detected by high-throughput techniques like qRT-PCR, microarray, and sequencing. Intracellular miRNAs could modulate mRNA activity through target-specific binding and play a crucial role in intercellular communications. At a pathological level, changes in cellular homeostasis lead to the modulation of molecular function of cells; as a result, miRNA expression is deregulated. Deregulated miRNAs came out from cells and frequently circulate in extracellular body fluids as part of various human diseases. Most common aging-associated diseases are cardiovascular disease, cancer, arthritis, dementia, cataract, osteoporosis, diabetes, hypertension, and neurodegenerative diseases such as Alzheimer's disease, Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Variation in the miRNA signature in a diseased peripheral circulatory system opens up a new avenue in the field of biomarker discovery. Here, we measure the biomarker potential of circulatory miRNAs in aging and various aging-related pathologies. However, further more confirmatory researches are needed to elaborate these findings at the translation level.

摘要

微小RNA(miRNA)存在于循环生物流体中,是衰老及与年龄相关疾病生物标志物研究的重要分子。血液或血液成分(血清/血浆)是循环miRNA的主要来源,这些miRNA可以以无细胞形式释放,要么与某些蛋白质成分结合,要么被称为外泌体的微泡颗粒包裹。miRNA在外周循环中相当稳定,可以通过qRT-PCR、微阵列和测序等高通量技术进行检测。细胞内的miRNA可通过特异性结合调节mRNA活性,并在细胞间通讯中发挥关键作用。在病理层面,细胞内稳态的变化会导致细胞分子功能的调节;结果,miRNA表达失调。失调的miRNA从细胞中释放出来,并经常作为各种人类疾病的一部分在外周体液中循环。最常见的与衰老相关的疾病有心血管疾病、癌症、关节炎、痴呆、白内障、骨质疏松症、糖尿病、高血压以及神经退行性疾病,如阿尔茨海默病、亨廷顿舞蹈症、帕金森病和肌萎缩侧索硬化症。患病外周循环系统中miRNA特征的变化为生物标志物发现领域开辟了一条新途径。在此,我们测定了循环miRNA在衰老及各种与衰老相关的病理状态下作为生物标志物的潜力。然而,需要更多的验证性研究来在转化层面阐明这些发现。

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