title: Age-dependent expression of DNMT1 and DNMT3B in PBMCs from a large European population enrolled in the MARK-AGE study.
abstract: Aging is associated with alterations in the content and patterns of DNA methylation virtually throughout the entire human lifespan. Reasons for these variations are not well understood. However, several lines of evidence suggest that the epigenetic instability in aging may be traced back to the alteration of the expression of DNA methyltransferases. Here, the association of the expression of DNA methyltransferases DNMT1 and DNMT3B with age has been analysed in the context of the MARK-AGE study, a large-scale cross-sectional study of the European general population. Using peripheral blood mononuclear cells, we assessed the variation of DNMT1 and DNMT3B gene expression in more than two thousand age-stratified women and men (35-75 years) recruited across eight European countries. Significant age-related changes were detected for both transcripts. The level of DNMT1 gradually dropped with aging but this was only observed up to the age of 64 years. By contrast, the expression of DNMT3B decreased linearly with increasing age and this association was particularly evident in females. We next attempted to trace the age-related changes of both transcripts to the influence of different variables that have an impact on changes of their expression in the population, including demographics, dietary and health habits, and clinical parameters. Our results indicate that age affects the expression of DNMT1 and DNMT3B as an almost independent variable in respect of all other variables evaluated.
authors.affiliation: Faculty of Pharmacy and Medicine, Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Rome, 00161, Italy.|Pasteur Institute-Fondazione Cenci Bolognetti, Rome, 00161, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Ciccarone
authors.affiliation: National Institute of Health and Science on Aging (INRCA), Nutrition and Ageing Centre, Scientific and Technological Research Area, 60100, Ancona, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Malavolta
authors.affiliation: Faculty of Pharmacy and Medicine, Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Rome, 00161, Italy.|Pasteur Institute-Fondazione Cenci Bolognetti, Rome, 00161, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Calabrese
authors.affiliation: Faculty of Pharmacy and Medicine, Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Rome, 00161, Italy.|Pasteur Institute-Fondazione Cenci Bolognetti, Rome, 00161, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Guastafierro
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum-University of Bologna, Bologna, 40126, Italy.|CIG-Interdepartmental Center 'L. Galvani', Alma Mater Studiorum, University of Bologna, 40126, Bologna, Italy.
authors.forename: Maria Giulia
authors.initials: MG
authors.lastname: Bacalini
authors.affiliation: Faculty of Pharmacy and Medicine, Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Rome, 00161, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Reale
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum-University of Bologna, Bologna, 40126, Italy.|CIG-Interdepartmental Center 'L. Galvani', Alma Mater Studiorum, University of Bologna, 40126, Bologna, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Franceschi
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum-University of Bologna, Bologna, 40126, Italy.|CIG-Interdepartmental Center 'L. Galvani', Alma Mater Studiorum, University of Bologna, 40126, Bologna, Italy.
authors.forename: Miriam
authors.initials: M
authors.lastname: Capri
authors.affiliation: The School of Medicine, The University of Tampere, 33014, Tampere, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Hervonen
authors.affiliation: The School of Medicine, The University of Tampere, 33014, Tampere, Finland.
authors.forename: Mikko
authors.initials: M
authors.lastname: Hurme
authors.affiliation: Research Institute for Biomedical Aging Research, Universität Innsbruck, Rennweg, 10, 6020, Innsbruck, Austria.
authors.forename: Beatrix
authors.initials: B
authors.lastname: Grubeck-Loebenstein
authors.affiliation: Department for Internal Medicine, University Teaching Hospital Hall in Tirol, Milserstr. 10, 6060, Hall in Tirol, Austria.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Koller
authors.affiliation: BioTeSys GmbH, 73728, Esslingen, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Bernhardt
authors.affiliation: BioTeSys GmbH, 73728, Esslingen, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Schӧn
authors.affiliation: Department of Molecular Epidemiology, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: P Eline
authors.initials: PE
authors.lastname: Slagboom
authors.affiliation: Research Unit on Cellular Biology, University of Namur, Rue de Bruxelles, 61, Namur, B-5000, Belgium.
authors.forename: Olivier
authors.initials: O
authors.lastname: Toussaint
authors.affiliation: Laboratory of the Molecular Bases of Ageing, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur Street, 02-093, Warsaw, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Sikora
authors.affiliation: National Hellenic Research Foundation, Institute of Biology, Medicinal Chemistry and Biotechnology, Athens, Greece.
authors.forename: Efstathios S
authors.initials: ES
authors.lastname: Gonos
authors.affiliation: Institute of Nutritional Medicine (180c), University of Hohenheim, Fruwirthstraße 12, 70599, Stuttgart, Germany.
authors.forename: Nicolle
authors.initials: N
authors.lastname: Breusing
authors.affiliation: German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany.
authors.forename: Tilman
authors.initials: T
authors.lastname: Grune
authors.affiliation: Centre for Health Protection, National Institute for Public Health and the Environment, PO Box 1, 3720, BA Bilthoven, The Netherlands.
authors.forename: Eugène
authors.initials: E
authors.lastname: Jansen
authors.affiliation: Centre for Health Protection, National Institute for Public Health and the Environment, PO Box 1, 3720, BA Bilthoven, The Netherlands.
authors.forename: Martijn
authors.initials: M
authors.lastname: Dollé
authors.affiliation: Molecular Toxicology Group, Department of Biology, University of Konstanz, 78457, Konstanz, Germany.
authors.forename: María
authors.initials: M
authors.lastname: Moreno-Villanueva
authors.affiliation: Molecular Toxicology Group, Department of Biology, University of Konstanz, 78457, Konstanz, Germany.
authors.forename: Thilo
authors.initials: T
authors.lastname: Sindlinger
authors.affiliation: Molecular Toxicology Group, Department of Biology, University of Konstanz, 78457, Konstanz, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Bürkle
authors.affiliation: Faculty of Pharmacy and Medicine, Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Rome, 00161, Italy.|Pasteur Institute-Fondazione Cenci Bolognetti, Rome, 00161, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Zampieri
authors.affiliation: Faculty of Pharmacy and Medicine, Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Rome, 00161, Italy.|Pasteur Institute-Fondazione Cenci Bolognetti, Rome, 00161, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Caiafa
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000235:genetics*; D015992:Body Mass Index; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics* / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D063990:Gene Ontology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000201:enzymology*; D008019:Life Style; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012044:Regression Analysis; D012307:Risk Factors; D044465:White People / Q000235:genetics*; D000097584:DNA Methyltransferase 3B
chemical_list: D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D012333:RNA, Messenger; D000097584:DNA Methyltransferase 3B; C000619380:DNMT1 protein, human
keywords: DNA methylation; DNMT1; DNMT3B; aging