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

Autor: Strasser, A., Trost, A., Grubeck-Loebenstein, B., Mück, C., Papak, C., Schreiner, C., Herndler-Brandstetter, D., Tschachler, E., Laschober, G., Lepperdinger, G., Kühnel, H., Grillari, J., Bauer, J.W., Fortschegger, K., Eckhard, L., Micutkova, L., Breitenbach, M., Hackl, M., Mildner, M., Rinnerthaler, M., Scheideler, M., Wieser, M., Sampson, N., Berger, P., Jansen-Dürr, P., Grillari-Voglauer, R., Brunner, S., Trajanoski, Z.
Jazyk: angličtina
Rok vydání: 2009
Předmět:
Popis: Aging is a multifactorial process where deterioration of body functions is driven by stochastic damage while counteracted by distinct genetically encoded repair systems. In order 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 4 replicative cell aging models including endothelial cells, replicated CD8+ 13 T cells, renal proximal tubular epithelial cells, and skin fibroblasts. Further included were three organismal aging models including foreskin, mesenchymal stem cells and CD8+ 16 T cell populations from old and young donors. Using LNA-based miRNA microarrays we identified four commonly regulated miRNAs, miR-17 down-regulated in all 7, miR-19b and miR-20a, down-regulated in 6 models and miR-106a down19 regulated in 5 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.
Databáze: OpenAIRE