miR-17, miR-19b, miR-20a, and miR-106a are down-regulated in human aging.
miR-17, miR-19b, miR-20a, and miR-106a are down-regulated in human aging.
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DOI：
10.1111/j.1474-9726.2010.00549.x
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发表时间：
2010-04
期刊：
影响因子：
7.8
通讯作者：
Grillari J
中科院分区：
文献类型：
--
作者：
Hackl M;Brunner S;Fortschegger K;Schreiner C;Micutkova L;Mück C;Laschober GT;Lepperdinger G;Sampson N;Berger P;Herndler-Brandstetter D;Wieser M;Kühnel H;Strasser A;Rinnerthaler M;Breitenbach M;Mildner M;Eckhart L;Tschachler E;Trost A;Bauer JW;Papak C;Trajanoski Z;Scheideler M;Grillari-Voglauer R;Grubeck-Loebenstein B;Jansen-Dürr P;Grillari J
衰老是一个多因素的过程，其中身体功能的退化是由随机损伤驱动的，同时由不同的遗传编码修复系统抵消。为了更好地理解衰老的遗传成分，许多研究已经解决了涉及从酵母到人类的不同生物体的各种衰老模型系统的基因和蛋白质表达谱。最近发现的小的非编码miRNA是有效的转录后调节剂，每个miRNA可以修改多达数百个靶基因的表达，类似于转录因子。越来越多的证据表明，mirna参与了包括衰老在内的大多数重要生理过程的调节。然而，到目前为止，mirna对年龄相关和衰老相关的基因表达变化的贡献仍然难以捉摸。为了解决这个问题，我们选择了四种复制细胞衰老模型，包括内皮细胞、复制CD8+ T细胞、肾近端小管上皮细胞和皮肤成纤维细胞。进一步纳入了三种机体衰老模型，包括包皮、间充质干细胞和来自老年和年轻供体的CD8+ T细胞群。利用锁定核酸为基础的miRNA微阵列，我们确定了四个常见的miRNA，其中miR-17在所有七个miRNA中下调；miR-19b和miR-20a在6个模型中下调；miR-106a在5个模型中下调。这些mirna的减少与一些既定靶基因的转录水平增加相关，特别是cdk抑制剂p21/CDKN1A。这些结果确立了mirna作为人类细胞衰老的新标记物。
Aging is a multifactorial process where deterioration of body functions is driven by stochastic damage while counteracted by distinct genetically encoded repair systems. To better understand the genetic component of aging, many studies have addressed the gene and protein expression profiles of various aging model systems engaging different organisms from yeast to human. The recently identified small non-coding miRNAs are potent post-transcriptional regulators that can modify the expression of up to several hundred target genes per single miRNA, similar to transcription factors. Increasing evidence shows that miRNAs contribute to the regulation of most if not all important physiological processes, including aging. However, so far the contribution of miRNAs to age-related and senescence-related changes in gene expression remains elusive. To address this question, we have selected four replicative cell aging models including endothelial cells, replicated CD8+ T cells, renal proximal tubular epithelial cells, and skin fibroblasts. Further included were three organismal aging models including foreskin, mesenchymal stem cells, and CD8+ T cell populations from old and young donors. Using locked nucleic acid-based miRNA microarrays, we identified four commonly regulated miRNAs, miR-17 down-regulated in all seven; miR-19b and miR-20a, down-regulated in six models; and miR-106a down-regulated in five models. Decrease in these miRNAs correlated with increased transcript levels of some established target genes, especially the cdk inhibitor p21/CDKN1A. These results establish miRNAs as novel markers of cell aging in humans.
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Mirbase：MicroRNA基因组学的工具。
影响因子：
14.9
作者：
Griffiths-Jones, Sam;Saini, Harpreet Kaur;van Dongen, Stijn;Enright, Anton J.
通讯作者：
Enright, Anton J.
影响因子：
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作者：
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影响因子：
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影响因子：
3.7
作者：
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通讯作者：
LEHMAN, JM
影响因子：
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作者：
Brazma A
通讯作者：
Brazma A