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Research Paper|Volume 7, Issue 2|pp 97—109

A meta-analysis on age-associated changes in blood DNA methylation: results from an original analysis pipeline for Infinium 450k data

Maria Giulia Bacalini1,2,3, Alessio Boattini4, Davide Gentilini5, Enrico Giampieri6, Chiara Pirazzini1,2, Cristina Giuliani4, Elisa Fontanesi1,2, Daniel Remondini6, Miriam Capri1,2, Alberto Del Rio1,7, Donata Luiselli4, Giovanni Vitale5,8, Daniela Mari8,9, Gastone Castellani6, Anna Maria Di Blasio5, Stefano Salvioli1,2, Claudio Franceschi1,2,10, Paolo Garagnani1,2,11
  • 1Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna 40138, Italy
  • 2Interdepartmental Center “L. Galvani”, University of Bologna, Bologna 40126, Italy
  • 3Personal Genomics S.r.l., Verona 37134, Italy
  • 4Department of Biological, Geological and Environmental Sciences, University of Bologna, Bologna 40126, Italy
  • 5Centro di Ricerche e Tecnologie Biomediche, Istituto Auxologico Italiano IRCCS, Cusano Milanino 20095, Italy
  • 6Department of Physics and Astronomy, University of Bologna, Bologna 40126, Italy
  • 7Institute of Organic Synthesis and Photoreactivity (ISOF) National Research Council (CNR), Bologna 40126, Italy
  • 8Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
  • 9Geriatric Unit, IRCCS Ca’ Granda Foundation Maggiore Policlinico Hospital, Milan, Italy
  • 10IRCCS Institute of Neurological Sciences, Bologna, Italy
  • 11Applied Biomedical Research Center, S. Orsola-Malpighi Polyclinic, Bologna 40138, Italy

* * Equal contribution

Received: December 23, 2014Accepted: January 9, 2015Published: January 11, 2015
https://doi.org/10.18632/aging.100718

Copyright: © 2015 Bacalini et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Aging is characterized by a profound remodeling of the epigenetic architecture in terms of DNA methylation patterns. To date the most effective tool to study genome wide DNA methylation changes is Infinium HumanMethylation450 BeadChip (Infinium 450k). Despite the wealth of tools for Infinium 450k analysis, the identification of the most biologically relevant DNA methylation changes is still challenging. Here we propose an analytical pipeline to select differentially methylated regions (DMRs), tailored on microarray architecture, which is highly effective in highlighting biologically relevant results. The pipeline groups microarray probes on the basis of their localization respect to CpG islands and genic sequences and, depending on probes density, identifies DMRs through a single-probe or a region-centric approach that considers the concomitant variation of multiple adjacent CpG probes. We successfully applied this analytical pipeline on 3 independent Infinium 450k datasets that investigated age-associated changes in blood DNA methylation. We provide a consensus list of genes that systematically vary in DNA methylation levels from 0 to 100 years and that have a potentially relevant role in the aging process.