Distinct DNA methylomes of newborns and centenarians

Holger Heyn, Ning Li, Humberto J. Ferreira, Sebastian Moran, David G. Pisano, Antonio Gomez, Javier Diez, Jose V. Sanchez-Mut, Fernando Setien, F. Javier Carmona, Annibale A. Puca, Sergi Sayols, Miguel A. Pujana, Jordi Serra-Musach, Isabel Iglesias-Platas, Francesc Formiga, Agustin F. Fernandez, Mario F. Fraga, Simon C. Heath, Alfonso ValenciaIvo G. Gut, Jun Wang, Manel Esteller

Research output: Contribution to journalArticlepeer-review

Abstract

Human aging cannot be fully understood in terms of the constrained genetic setting. Epigenetic drift is an alternative means of explaining age-associated alterations. To address this issue, we performed whole-genome bisulfite sequencing (WGBS) of newborn and centenarian genomes. The centenarian DNA had a lower DNA methylation content and a reduced correlation in the methylation status of neighboring cytosine - phosphate - guanine (CpGs) throughout the genome in comparison with the more homogeneously methylated newborn DNA. The more hypomethylated CpGs observed in the centenarian DNA compared with the neonate covered all genomic compartments, such as promoters, exonic, intronic, and intergenic regions. For regulatory regions, the most hypomethylated sequences in the centenarian DNA were present mainly at CpG-poor promoters and in tissue-specific genes, whereas a greater level of DNA methylation was observed in CpG island promoters. We extended the study to a larger cohort of newborn and nonagenarian samples using a 450,000 CpG-site DNA methylation microarray that reinforced the observation of more hypomethylated DNA sequences in the advanced age group. WGBS and 450,000 analyses of middle-age individuals demonstrated DNA methylomes in the crossroad between the newborn and the nonagenarian/centenarian groups. Our study constitutes a unique DNA methylation analysis of the extreme points of human life at a single-nucleotide resolution level.

Original languageEnglish
Pages (from-to)10522-10527
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number26
DOIs
Publication statusPublished - Jun 26 2012

Keywords

  • Epigenomics
  • Longevity

ASJC Scopus subject areas

  • General

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