miR-17, miR-19b, miR-20a, and miR-106a are down-regulated in human aging

被引:306
作者
Hackl, Matthias [1 ]
Brunner, Stefan [2 ]
Fortschegger, Klaus [1 ]
Schreiner, Carina [1 ]
Micutkova, Lucia [3 ]
Mueck, Christoph [3 ]
Laschober, Gerhard T. [4 ]
Lepperdinger, Guenter [4 ]
Sampson, Natalie [5 ]
Berger, Peter [5 ]
Herndler-Brandstetter, Dietmar [2 ]
Wieser, Matthias [1 ]
Kuehnel, Harald [6 ]
Strasser, Alois [6 ]
Rinnerthaler, Mark [7 ]
Breitenbach, Michael [7 ]
Mildner, Michael [8 ]
Eckhart, Leopold [8 ]
Tschachler, Erwin [8 ]
Trost, Andrea [9 ]
Bauer, Johann W. [9 ]
Papak, Christine [10 ,11 ]
Trajanoski, Zlatko [10 ,11 ]
Scheideler, Marcel [10 ,11 ]
Grillari-Voglauer, Regina [1 ]
Grubeck-Loebenstein, Beatrix [2 ]
Jansen-Duerr, Pidder [3 ]
Grillari, Johannes [1 ]
机构
[1] Univ Nat Resources & Appl Life Sci, Dept Biotechnol, A-1190 Vienna, Austria
[2] Austrian Acad Sci, Inst Biomed Aging Res, Dept Immunol, A-6020 Innsbruck, Austria
[3] Austrian Acad Sci, Inst Biomed Aging Res, Dept Mol & Cell Biol, A-6020 Innsbruck, Austria
[4] Austrian Acad Sci, Inst Biomed Aging Res, Dept Extracellular Matrix Res, A-6020 Innsbruck, Austria
[5] Austrian Acad Sci, Inst Biomed Aging Res, Dept Endocrinol, A-6020 Innsbruck, Austria
[6] Univ Vet Med Vienna, Inst Physiol, Dept Nat Sci, A-1210 Vienna, Austria
[7] Salzburg Univ, Dept Genet, A-5020 Salzburg, Austria
[8] Med Univ Vienna, Dept Dermatol, A-1090 Vienna, Austria
[9] SALK & Paracelsus Med Univ, Dept Dermatol, Salzburg, Austria
[10] Graz Univ Technol, Inst Genom & Bioinformat, A-8010 Graz, Austria
[11] Graz Univ Technol, Christian Doppler Lab Genom & Bioinformat, A-8010 Graz, Austria
基金
奥地利科学基金会;
关键词
aging; miR-106a; miR-17; miR-17-92; cluster; miR-19b; miR-20a; miRNA microarray; p21 (CDKN1A); senescence; MESENCHYMAL STEM-CELLS; MICRORNA EXPRESSION; REPLICATIVE SENESCENCE; HUMAN FIBROBLASTS; P53; CLUSTER; AGE; REPRESSION; MIRNAS; CANCER;
D O I
10.1111/j.1474-9726.2010.00549.x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:291 / 296
页数:6
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