Reverse Expression of Aging-Associated Molecules through Transfection of miRNAs to Aged Mice.
Reverse Expression of Aging-Associated Molecules through Transfection of miRNAs to Aged Mice.
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DOI：
10.1016/j.omtn.2016.11.005
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发表时间：
2017-03-17
期刊：
影响因子：
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通讯作者：
Kim E
中科院分区：
文献类型：
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作者：
Kim JH;Lee BR;Choi ES;Lee KM;Choi SK;Cho JH;Jeon WB;Kim E
衰老过程中的分子变化已被研究，以了解衰老进程的机制。在本文中，研究了小鼠全血中microRNA（miRNA）表达的变化，以系统地逆转衰老，并提出它们作为非侵入性生物标志物。通过下一代测序分析，我们选择了27个在衰老过程中差异表达的miRNA。最公认的功能是肝脏脂肪变性，一种非酒精性脂肪性肝病（NAFLD）。在27种miRNA中，预测有6种参与NAFLD，即miR-16- 5 p、miR-17- 5 p、miR-21 a-5 p、miR-30 c-5 p、miR-103- 3 p和miR-130 a-3 p;通过实时qPCR证实了其血液和肝脏水平的变化。这些miRNAs网络中相关基因Bcl 2、Ppara、E2 f1、E2 f2、Akt、Ccnd 1和Smad 2/3的表达在老年小鼠的肝脏中也发生了改变。在将这些miRNA转染到18月龄小鼠中后，miR-21 a-5 p、miR-103- 3 p和miR-30 c-5 p的水平增加，并且其相关基因在肝脏中表现出逆转表达。据报道，Mre 11 a、p16 INK 4a和Mtor是衰老相关分子，它们的表达在miRNA转染小鼠的肝脏中也被逆转。这些miRNAs可能是衰老的非侵入性生物标志物，它们可能诱导衰老相关通路的反向调节。本研究为逆转衰老提供了初步数据，可进一步应用于成人疾病的治疗。
Molecular changes during aging have been studied to understand the mechanism of aging progress. Herein, changes in microRNA (miRNA) expression in the whole blood of mice were studied to systemically reverse aging and propose them as non-invasive biomarkers. Through next-generation sequencing analysis, we selected 27 differentially expressed miRNAs during aging. The most recognized function involved was liver steatosis, a type of non-alcoholic fatty liver disease (NAFLD). Among 27 miRNAs, six were predicted to be involved in NAFLD, miR-16-5p, miR-17-5p, miR-21a-5p, miR-30c-5p, miR-103-3p, and miR-130a-3p; alterations in their blood and liver levels were confirmed by real-time qPCR. The expression of the genes associated in the network of these miRNAs, Bcl2, Ppara, E2f1, E2f2, Akt, Ccnd1, and Smad2/3, also was altered in the liver of aged mice. Following transfection of these miRNAs into 18-month-old mice, levels of miR-21a-5p, miR-103-3p, and miR-30c-5p increased, and their related genes exhibited a reversed expression in the liver. Expression of Mre11a, p16INK4a, and Mtor, reported to be aging-associated molecules, also was reversed in the livers of miRNA-transfected mice. These miRNAs could be non-invasive biomarkers for aging, and they might induce a reverse regulation of aging-associated pathways. This study provides preliminary data on reverse aging, which could be applied further for treatments of adult diseases.