Specific age-associated DNA methylation changes in human dermal fibroblasts.

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 development...

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Autores principales:	Carmen M Koch, Christoph V Suschek, Qiong Lin, Simone Bork, Maria Goergens, Sylvia Joussen, Norbert Pallua, Anthony D Ho, Martin Zenke, Wolfgang Wagner
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/552d19d59cd24deaa2c6dcc3df476c0e
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spelling	oai:doaj.org-article:552d19d59cd24deaa2c6dcc3df476c0e2021-11-18T06:59:07ZSpecific age-associated DNA methylation changes in human dermal fibroblasts.1932-620310.1371/journal.pone.0016679https://doaj.org/article/552d19d59cd24deaa2c6dcc3df476c0e2011-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21347436/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Epigenetic 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 closely together indicating that fibroblasts maintain positional memory even after in vitro culture. 75 CpG sites were more than 15% differentially methylated in fibroblasts upon aging. Very high hyper-methylation was observed in the aged group within the INK4A/ARF/INK4b locus and this was validated by pyrosequencing. Age-associated DNA methylation changes were related in fibroblasts and MSC but they were often regulated in opposite directions between the two cell types. In contrast, long-term culture associated changes were very consistent in fibroblasts and MSC. Epigenetic modifications at specific CpG sites support the notion that aging represents a coordinated developmental mechanism that seems to be regulated in a cell type specific manner.Carmen M KochChristoph V SuschekQiong LinSimone BorkMaria GoergensSylvia JoussenNorbert PalluaAnthony D HoMartin ZenkeWolfgang WagnerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 2, p e16679 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Carmen M Koch Christoph V Suschek Qiong Lin Simone Bork Maria Goergens Sylvia Joussen Norbert Pallua Anthony D Ho Martin Zenke Wolfgang Wagner Specific age-associated DNA methylation changes in human dermal fibroblasts.
description	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 closely together indicating that fibroblasts maintain positional memory even after in vitro culture. 75 CpG sites were more than 15% differentially methylated in fibroblasts upon aging. Very high hyper-methylation was observed in the aged group within the INK4A/ARF/INK4b locus and this was validated by pyrosequencing. Age-associated DNA methylation changes were related in fibroblasts and MSC but they were often regulated in opposite directions between the two cell types. In contrast, long-term culture associated changes were very consistent in fibroblasts and MSC. Epigenetic modifications at specific CpG sites support the notion that aging represents a coordinated developmental mechanism that seems to be regulated in a cell type specific manner.
format	article
author	Carmen M Koch Christoph V Suschek Qiong Lin Simone Bork Maria Goergens Sylvia Joussen Norbert Pallua Anthony D Ho Martin Zenke Wolfgang Wagner
author_facet	Carmen M Koch Christoph V Suschek Qiong Lin Simone Bork Maria Goergens Sylvia Joussen Norbert Pallua Anthony D Ho Martin Zenke Wolfgang Wagner
author_sort	Carmen M Koch
title	Specific age-associated DNA methylation changes in human dermal fibroblasts.
title_short	Specific age-associated DNA methylation changes in human dermal fibroblasts.
title_full	Specific age-associated DNA methylation changes in human dermal fibroblasts.
title_fullStr	Specific age-associated DNA methylation changes in human dermal fibroblasts.
title_full_unstemmed	Specific age-associated DNA methylation changes in human dermal fibroblasts.
title_sort	specific age-associated dna methylation changes in human dermal fibroblasts.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/552d19d59cd24deaa2c6dcc3df476c0e
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Specific age-associated DNA methylation changes in human dermal fibroblasts.

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