Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

DNA methylomes of Newborns and Nonagenarians

ABSTRACT: DNA methylation differences between Newborns and Nonagenarians The study aimed to compare the DNA methylation differences between newborns and nonagenarians using methylation array technology (450K, Illumina). The identified differently methylated CpG were further analyzed for their presence in diseases related to the aging phenotype (Werner and Progeria syndrome).

ORGANISM(S): Homo sapiens

SUBMITTER: Antonio Gómez

PROVIDER: E-GEOD-30870 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Distinct DNA methylomes of newborns and centenarians.

Heyn Holger H Li Ning N Ferreira Humberto J HJ Moran Sebastian S Pisano David G DG Gomez Antonio A Diez Javier J Sanchez-Mut Jose V JV Setien Fernando F Carmona F Javier FJ Puca Annibale A AA Sayols Sergi S Pujana Miguel A MA Serra-Musach Jordi J Iglesias-Platas Isabel I Formiga Francesc F Fernandez Agustin F AF Fraga Mario F MF Heath Simon C SC Valencia Alfonso A Gut Ivo G IG Wang Jun J Wang Jun J Esteller Manel M

Proceedings of the National Academy of Sciences of the United States of America 20120611 26

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 homogeneous ...[more]

PMID: 22689993

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Project description:Human aging implies many phenotypic modifications and an increased susceptibility to many common diseases, phenomena that cannot be fully explained by the constrained genetic setting. An alternative pathway that could explain the age-associated alterations is epigenetic drifts. To address this issue, we performed Whole Genome Bisulfite Sequencing (WGBS) of a newborn and of a centenarian. The centenarian DNA exhibited a significant loss in DNA methylation and a poor correlation in the methylation status of neighboring CpGs throughout the genome. From a gene-regulatory region standpoint, we observed that the DNA hypomethylation events occurred mainly at CpG-poor promoters and in tissue-specific genes, whereas a greater level of DNA methylation was observed in CpG island promoters. Most importantly, we extended the study to a larger cohort of newborn and nonagenarian samples using a 450,000 CpG-site DNA methylation microarray. The 450K DNA methylation approach enabled validation of the WGBS data and revealed additional age-related DNA methylation events. Interestingly, we also observed the DNA methylation fingerprint characteristic of a healthy aged cell in samples from patients with premature-aging disorders such as Hutchinson-Gilford progeria and Werner syndrome. Overall, we suggest that defects in the physiological DNA methylation profile contribute to the process of human aging. As the disease associated cells were immortalized B cells, the effect of EBV immortalization was determined in advance to the study using immortalized and naive B cells. DNA was quantified by Quant-iT PicoGreen dsDNA Reagent (Invitrogen) and the integrity was analyzed in a 1.3% agarose gel. Bisulfite conversion of 600 ng of each sample was perform according to the manufacturer's recommendation for Illumina Infinium Assay. Effective bisulphite conversion was checked for three controls that were converted simultaneously with the samples. 4 ul of bisulfite converted DNA were used to hybridize on Infinium HumanMethylation 450 BeadChip, following Illumina Infinium HD Methylation protocol. Chip analysis was performed using Illumina HiScan SQ fluorescent scanner. The intensities of the images are extracted using GenomeStudio (2010.3) Methylation module (1.8.5) software. Methylation score of each CpG is represented as beta value.

Dataset Information

DNA methylomes of Newborns and Nonagenarians

Publications

Distinct DNA methylomes of newborns and centenarians.

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