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DNA Hydroxymethylation Levels Are Altered in Blood Cells From Down Syndrome Persons Enrolled in the MARK-AGE Project

Down syndrome (DS) is caused by the presence of part or an entire extra copy of chromosome 21, a phenomenon that can cause a wide spectrum of clinically defined phenotypes of the disease. Most of the clinical signs of DS are typical of the aging process including dysregulation of immune system. Beyo...

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Autores principales: Ciccarone, Fabio, Valentini, Elisabetta, Malavolta, Marco, Zampieri, Michele, Bacalini, Maria Giulia, Calabrese, Roberta, Guastafierro, Tiziana, Reale, Anna, Franceschi, Claudio, Capri, Miriam, Breusing, Nicolle, Grune, Tilman, Moreno‐Villanueva, María, Bürkle, Alexander, Caiafa, Paola
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5946825/
https://www.ncbi.nlm.nih.gov/pubmed/29069286
http://dx.doi.org/10.1093/gerona/glx198
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author Ciccarone, Fabio
Valentini, Elisabetta
Malavolta, Marco
Zampieri, Michele
Bacalini, Maria Giulia
Calabrese, Roberta
Guastafierro, Tiziana
Reale, Anna
Franceschi, Claudio
Capri, Miriam
Breusing, Nicolle
Grune, Tilman
Moreno‐Villanueva, María
Bürkle, Alexander
Caiafa, Paola
author_facet Ciccarone, Fabio
Valentini, Elisabetta
Malavolta, Marco
Zampieri, Michele
Bacalini, Maria Giulia
Calabrese, Roberta
Guastafierro, Tiziana
Reale, Anna
Franceschi, Claudio
Capri, Miriam
Breusing, Nicolle
Grune, Tilman
Moreno‐Villanueva, María
Bürkle, Alexander
Caiafa, Paola
author_sort Ciccarone, Fabio
collection PubMed
description Down syndrome (DS) is caused by the presence of part or an entire extra copy of chromosome 21, a phenomenon that can cause a wide spectrum of clinically defined phenotypes of the disease. Most of the clinical signs of DS are typical of the aging process including dysregulation of immune system. Beyond the causative genetic defect, DS persons display epigenetic alterations, particularly aberrant DNA methylation patterns that can contribute to the heterogeneity of the disease. In the present work, we investigated the levels of 5-hydroxymethylcytosine and of the Ten-eleven translocation dioxygenase enzymes, which are involved in DNA demethylation processes and are often deregulated in pathological conditions as well as in aging. Analyses were carried out on peripheral blood mononuclear cells of DS volunteers enrolled in the context of the MARK-AGE study, a large-scale cross-sectional population study with subjects representing the general population in eight European countries. We observed a decrease in 5-hydroxymethylcytosine, TET1, and other components of the DNA methylation/demethylation machinery in DS subjects, indicating that aberrant DNA methylation patterns in DS, which may have consequences on the transcriptional status of immune cells, may be due to a global disturbance of methylation control in DS.
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spelling pubmed-59468252018-05-15 DNA Hydroxymethylation Levels Are Altered in Blood Cells From Down Syndrome Persons Enrolled in the MARK-AGE Project Ciccarone, Fabio Valentini, Elisabetta Malavolta, Marco Zampieri, Michele Bacalini, Maria Giulia Calabrese, Roberta Guastafierro, Tiziana Reale, Anna Franceschi, Claudio Capri, Miriam Breusing, Nicolle Grune, Tilman Moreno‐Villanueva, María Bürkle, Alexander Caiafa, Paola J Gerontol A Biol Sci Med Sci The Journal of Gerontology: Biological Sciences Down syndrome (DS) is caused by the presence of part or an entire extra copy of chromosome 21, a phenomenon that can cause a wide spectrum of clinically defined phenotypes of the disease. Most of the clinical signs of DS are typical of the aging process including dysregulation of immune system. Beyond the causative genetic defect, DS persons display epigenetic alterations, particularly aberrant DNA methylation patterns that can contribute to the heterogeneity of the disease. In the present work, we investigated the levels of 5-hydroxymethylcytosine and of the Ten-eleven translocation dioxygenase enzymes, which are involved in DNA demethylation processes and are often deregulated in pathological conditions as well as in aging. Analyses were carried out on peripheral blood mononuclear cells of DS volunteers enrolled in the context of the MARK-AGE study, a large-scale cross-sectional population study with subjects representing the general population in eight European countries. We observed a decrease in 5-hydroxymethylcytosine, TET1, and other components of the DNA methylation/demethylation machinery in DS subjects, indicating that aberrant DNA methylation patterns in DS, which may have consequences on the transcriptional status of immune cells, may be due to a global disturbance of methylation control in DS. Oxford University Press 2018-05 2017-10-21 /pmc/articles/PMC5946825/ /pubmed/29069286 http://dx.doi.org/10.1093/gerona/glx198 Text en © The Author(s) 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle The Journal of Gerontology: Biological Sciences
Ciccarone, Fabio
Valentini, Elisabetta
Malavolta, Marco
Zampieri, Michele
Bacalini, Maria Giulia
Calabrese, Roberta
Guastafierro, Tiziana
Reale, Anna
Franceschi, Claudio
Capri, Miriam
Breusing, Nicolle
Grune, Tilman
Moreno‐Villanueva, María
Bürkle, Alexander
Caiafa, Paola
DNA Hydroxymethylation Levels Are Altered in Blood Cells From Down Syndrome Persons Enrolled in the MARK-AGE Project
title DNA Hydroxymethylation Levels Are Altered in Blood Cells From Down Syndrome Persons Enrolled in the MARK-AGE Project
title_full DNA Hydroxymethylation Levels Are Altered in Blood Cells From Down Syndrome Persons Enrolled in the MARK-AGE Project
title_fullStr DNA Hydroxymethylation Levels Are Altered in Blood Cells From Down Syndrome Persons Enrolled in the MARK-AGE Project
title_full_unstemmed DNA Hydroxymethylation Levels Are Altered in Blood Cells From Down Syndrome Persons Enrolled in the MARK-AGE Project
title_short DNA Hydroxymethylation Levels Are Altered in Blood Cells From Down Syndrome Persons Enrolled in the MARK-AGE Project
title_sort dna hydroxymethylation levels are altered in blood cells from down syndrome persons enrolled in the mark-age project
topic The Journal of Gerontology: Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5946825/
https://www.ncbi.nlm.nih.gov/pubmed/29069286
http://dx.doi.org/10.1093/gerona/glx198
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