specific age-associated dna methylation changes in human dermal fibroblasts人类皮肤成纤维细胞特定的与年龄有关的dna甲基化的变化.pdf

Specific Age-Associated DNA Methylation Changes in Human Dermal Fibroblasts 1. 2. 1 3,4 2 Carmen M. Koch , Christoph V. Suschek , Qiong Lin , Simone Bork , Maria Goergens , Sylvia 1 2 3 1 1 Joussen , Norbert Pallua , Anthony D. Ho , Martin Zenke , Wolfgang Wagner * 1 Helmholtz-Institute for Biomedical Engineering, RWTH Aachen University Medical School, Aachen, Germany, 2 Department of Plastic and Reconstructive Surgery, Hand Surgery, Burn Center, RWTH Aachen University Medical School, Aachen, Germany, 3 Department of Medicine V, University of Heidelberg, Heidelberg, Germany, 4 Heidelberg Academy of Sciences and Humanities, Heidelberg, Germany Abstract Epigenetic modifications of cytosine residues in the DNA play a critical role for cellular differentiation and potentially also for aging. In mesenchymal stromal cells (MSC) from human bone marrow we have previously demonstrated age-associated methylation changes at specific CpG-sites of developmental genes. In continuation of this work, we have now isolated human dermal fibroblasts from young (,23 years) and elderly donors (.60 years) for comparison of their DNA methylation profiles using the Infinium HumanMethylation27 assay. In contrast to MSC, fibroblasts could not be induced towards adipogenic, osteogenic and chondrogenic lineage and this is reflected by highly significant differences between the two cell types: 766 CpG sites were hyper-methylated and 752 CpG sites were hypo-methylated in fibroblasts in comparison to MSC. Strikingly, global DNA methylation profiles of fibroblasts from the same dermal region clustered c