Age-dependent expression of DNMT1 and DNMT3B in PBMCs from a large European population enrolled in the MARK-AGE study.

Fabio Ciccarone, Marco Malavolta, Roberta Calabrese, Tiziana Guastafierro, Maria Giulia Bacalini, Anna Reale, Claudio Franceschi, Miriam Capri, Antti Hervonen, Mikko Hurme, Beatrix Grubeck-Loebenstein, Bernhard Koller, Jürgen Bernhardt, Christiane Schӧn, P Eline Slagboom, Olivier Toussaint, Ewa Sikora, Efstathios S Gonos, Nicolle Breusing, Tilman Grune, Eugène Jansen, Martijn Dollé, María Moreno-Villanueva, Thilo Sindlinger, Alexander Bürkle, Michele Zampieri, Paola Caiafa

Journal: Aging cell 2017;15(4):755-65

PMID: 27169697

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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.

Address: 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.; National Institute of Health and Science on Aging (INRCA), Nutrition and Ageing Centre, Scientific and Technological Research Area, 60100, Ancona, Italy.; 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.; Faculty of Pharmacy and Medicine, Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Rome, 00161, Italy.; The School of Medicine, The University of Tampere, 33014, Tampere, Finland.; Research Institute for Biomedical Aging Research, Universität Innsbruck, Rennweg, 10, 6020, Innsbruck, Austria.; Department for Internal Medicine, University Teaching Hospital Hall in Tirol, Milserstr. 10, 6060, Hall in Tirol, Austria.; BioTeSys GmbH, 73728, Esslingen, Germany.; Department of Molecular Epidemiology, Leiden University Medical Centre, Leiden, The Netherlands.; Research Unit on Cellular Biology, University of Namur, Rue de Bruxelles, 61, Namur, B-5000, Belgium.; Laboratory of the Molecular Bases of Ageing, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur Street, 02-093, Warsaw, Poland.; National Hellenic Research Foundation, Institute of Biology, Medicinal Chemistry and Biotechnology, Athens, Greece.; Institute of Nutritional Medicine (180c), University of Hohenheim, Fruwirthstraße 12, 70599, Stuttgart, Germany.; German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany.; Centre for Health Protection, National Institute for Public Health and the Environment, PO Box 1, 3720, BA Bilthoven, The Netherlands.; Molecular Toxicology Group, Department of Biology, University of Konstanz, 78457, Konstanz, Germany.

DOI: 10.1111/acel.12485

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MeSH Terms: Adult, Aged, Aging, Body Mass Index, DNA (Cytosine-5-)-Methyltransferase 1, DNA (Cytosine-5-)-Methyltransferases, Female, Gene Expression Regulation, Developmental, Gene Expression Regulation, Enzymologic, Gene Ontology, Humans, Leukocytes, Mononuclear, Life Style, Male, Middle Aged, RNA, Messenger, Regression Analysis, Risk Factors, White People, DNA Methyltransferase 3B