miR-17, miR-19b, miR-20a, and miR-106a are down-regulated in human aging.
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.
Hackl
Matthias
M
Department of Biotechnology, University of Natural Resources and Applied Life Sciences, Vienna, Austria.
Brunner
Stefan
S
Fortschegger
Klaus
K
Schreiner
Carina
C
Micutkova
Lucia
L
Mück
Christoph
C
Laschober
Gerhard T
GT
Lepperdinger
Günter
G
Sampson
Natalie
N
Berger
Peter
P
Herndler-Brandstetter
Dietmar
D
Wieser
Matthias
M
Kühnel
Harald
H
Strasser
Alois
A
Rinnerthaler
Mark
M
Breitenbach
Michael
M
Mildner
Michael
M
Eckhart
Leopold
L
Tschachler
Erwin
E
Trost
Andrea
A
Bauer
Johann W
JW
Papak
Christine
C
Trajanoski
Zlatko
Z
Scheideler
Marcel
M
Grillari-Voglauer
Regina
R
Grubeck-Loebenstein
Beatrix
B
Jansen-Dürr
Pidder
P
Grillari
Johannes
J
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
C542541:MIRN106 microRNA, human; C524941:MIRN17 microRNA, human; C549214:MIRN19A microRNA, human; C534451:MIRN20a microRNA, human; D035683:MicroRNAs