title: miR-17, miR-19b, miR-20a, and miR-106a are down-regulated in human aging.
abstract: 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.
authors.affiliation: Department of Biotechnology, University of Natural Resources and Applied Life Sciences, Vienna, Austria.
authors.forename: Matthias
authors.initials: M
authors.lastname: Hackl
authors.forename: Stefan
authors.initials: S
authors.lastname: Brunner
authors.forename: Klaus
authors.initials: K
authors.lastname: Fortschegger
authors.forename: Carina
authors.initials: C
authors.lastname: Schreiner
authors.forename: Lucia
authors.initials: L
authors.lastname: Micutkova
authors.forename: Christoph
authors.initials: C
authors.lastname: Mück
authors.forename: Gerhard T
authors.initials: GT
authors.lastname: Laschober
authors.forename: Günter
authors.initials: G
authors.lastname: Lepperdinger
authors.forename: Natalie
authors.initials: N
authors.lastname: Sampson
authors.forename: Peter
authors.initials: P
authors.lastname: Berger
authors.forename: Dietmar
authors.initials: D
authors.lastname: Herndler-Brandstetter
authors.forename: Matthias
authors.initials: M
authors.lastname: Wieser
authors.forename: Harald
authors.initials: H
authors.lastname: Kühnel
authors.forename: Alois
authors.initials: A
authors.lastname: Strasser
authors.forename: Mark
authors.initials: M
authors.lastname: Rinnerthaler
authors.forename: Michael
authors.initials: M
authors.lastname: Breitenbach
authors.forename: Michael
authors.initials: M
authors.lastname: Mildner
authors.forename: Leopold
authors.initials: L
authors.lastname: Eckhart
authors.forename: Erwin
authors.initials: E
authors.lastname: Tschachler
authors.forename: Andrea
authors.initials: A
authors.lastname: Trost
authors.forename: Johann W
authors.initials: JW
authors.lastname: Bauer
authors.forename: Christine
authors.initials: C
authors.lastname: Papak
authors.forename: Zlatko
authors.initials: Z
authors.lastname: Trajanoski
authors.forename: Marcel
authors.initials: M
authors.lastname: Scheideler
authors.forename: Regina
authors.initials: R
authors.lastname: Grillari-Voglauer
authors.forename: Beatrix
authors.initials: B
authors.lastname: Grubeck-Loebenstein
authors.forename: Pidder
authors.initials: P
authors.lastname: Jansen-Dürr
authors.forename: Johannes
authors.initials: J
authors.lastname: Grillari
mesh_terms: D000375:Aging; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D015536:Down-Regulation; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: C542541:MIRN106 microRNA, human; C524941:MIRN17 microRNA, human; C549214:MIRN19A microRNA, human; C534451:MIRN20a microRNA, human; D035683:MicroRNAs