DNA hydroxymethylation levels are altered in blood cells from Down syndrome persons enrolled in the MARK-AGE project

Fabio Ciccarone, Elisabetta Valentini, Marco Malavolta, Michele Zampieri, Maria Giulia Bacalini, Roberta Calabrese, Tiziana Guastafierro, Anna Reale, Claudio Franceschi, Miriam Capri, Nicolle Breusing, Tilman Grune, María Moreno-Villanueva, Alexander Bürkle, Paola Caiafa

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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 ageing 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 (5hmC) and of the TET dioxygenase enzymes, which are involved in DNA demethylation processes and are often deregulated in pathological conditions as well as in ageing. 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 of 5hmC, 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.

Original languageEnglish
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
DOIs
Publication statusE-pub ahead of print - Oct 21 2017

Fingerprint

Down Syndrome
Blood Cells
DNA
DNA Methylation
Dioxygenases
Chromosomes, Human, Pair 21
Epigenomics
Methylation
Population
Volunteers
Immune System
Cross-Sectional Studies
Phenotype
Enzymes

Cite this

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.

In: Journals of Gerontology - Series A Biological Sciences and Medical Sciences, 21.10.2017.

Research output: Contribution to journalArticle

Ciccarone, F, Valentini, E, Malavolta, M, Zampieri, M, Bacalini, MG, Calabrese, R, Guastafierro, T, Reale, A, Franceschi, C, Capri, M, Breusing, N, Grune, T, Moreno-Villanueva, M, Bürkle, A & Caiafa, P 2017, 'DNA hydroxymethylation levels are altered in blood cells from Down syndrome persons enrolled in the MARK-AGE project', Journals of Gerontology - Series A Biological Sciences and Medical Sciences. https://doi.org/10.1093/gerona/glx198
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. In: Journals of Gerontology - Series A Biological Sciences and Medical Sciences. 2017.
@article{c5c0b5e635e140b3a2cdec84abf017a6,
title = "DNA hydroxymethylation levels are altered in blood cells from Down syndrome persons enrolled in the MARK-AGE project",
abstract = "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 ageing 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 (5hmC) and of the TET dioxygenase enzymes, which are involved in DNA demethylation processes and are often deregulated in pathological conditions as well as in ageing. 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 of 5hmC, 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.",
author = "Fabio Ciccarone and Elisabetta Valentini and Marco Malavolta and Michele Zampieri and Bacalini, {Maria Giulia} and Roberta Calabrese and Tiziana Guastafierro and Anna Reale and Claudio Franceschi and Miriam Capri and Nicolle Breusing and Tilman Grune and Mar{\'i}a Moreno-Villanueva and Alexander B{\"u}rkle and Paola Caiafa",
note = "{\circledC} The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America.",
year = "2017",
month = "10",
day = "21",
doi = "10.1093/gerona/glx198",
language = "English",
journal = "Journals of Gerontology - Series A Biological Sciences and Medical Sciences",
issn = "1079-5006",
publisher = "Oxford University Press",

}

TY - JOUR

T1 - DNA hydroxymethylation levels are altered in blood cells from Down syndrome persons enrolled in the MARK-AGE project

AU - Ciccarone, Fabio

AU - Valentini, Elisabetta

AU - Malavolta, Marco

AU - Zampieri, Michele

AU - Bacalini, Maria Giulia

AU - Calabrese, Roberta

AU - Guastafierro, Tiziana

AU - Reale, Anna

AU - Franceschi, Claudio

AU - Capri, Miriam

AU - Breusing, Nicolle

AU - Grune, Tilman

AU - Moreno-Villanueva, María

AU - Bürkle, Alexander

AU - Caiafa, Paola

N1 - © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America.

PY - 2017/10/21

Y1 - 2017/10/21

N2 - 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 ageing 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 (5hmC) and of the TET dioxygenase enzymes, which are involved in DNA demethylation processes and are often deregulated in pathological conditions as well as in ageing. 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 of 5hmC, 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.

AB - 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 ageing 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 (5hmC) and of the TET dioxygenase enzymes, which are involved in DNA demethylation processes and are often deregulated in pathological conditions as well as in ageing. 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 of 5hmC, 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.

U2 - 10.1093/gerona/glx198

DO - 10.1093/gerona/glx198

M3 - Article

C2 - 29069286

JO - Journals of Gerontology - Series A Biological Sciences and Medical Sciences

JF - Journals of Gerontology - Series A Biological Sciences and Medical Sciences

SN - 1079-5006

ER -