Distinct DNA methylomes of newborns and centenarians

被引:579
|
作者
Heyn, Holger [2 ]
Li, Ning [4 ,5 ]
Ferreira, Humberto J. [2 ,6 ]
Moran, Sebastian [2 ]
Pisano, David G. [7 ]
Gomez, Antonio [2 ]
Diez, Javier [2 ]
Sanchez-Mut, Jose V. [2 ]
Setien, Fernando [2 ]
Javier Carmona, F. [2 ]
Puca, Annibale A. [8 ,9 ]
Sayols, Sergi [2 ]
Pujana, Miguel A. [3 ]
Serra-Musach, Jordi [3 ]
Iglesias-Platas, Isabel [10 ]
Formiga, Francesc [11 ]
Fernandez, Agustin F. [12 ]
Fraga, Mario F. [12 ,13 ]
Heath, Simon C. [14 ]
Valencia, Alfonso [7 ]
Gut, Ivo G. [14 ]
Wang, Jun [1 ,15 ]
Esteller, Manel [2 ,16 ,17 ]
机构
[1] Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark
[2] Bellvitge Biomed Res Inst, Catalan Inst Oncol, Canc Epigenet & Biol Program, Barcelona 08908, Catalonia, Spain
[3] Bellvitge Biomed Res Inst, Catalan Inst Oncol, Biomarkers & Susceptibil Unit, Spanish Biomed Res Ctr Network Epidemiol & Publ H, Barcelona 08908, Catalonia, Spain
[4] Beijing Genom Inst Europe, DK-2200 Copenhagen N, Denmark
[5] Beijing Genom Inst, Shenzhen, Guangdong, Peoples R China
[6] Univ Coimbra, Ctr Neurosci & Cell Biol, Programme Expt Biol & Biomed, P-3000 Coimbra, Portugal
[7] Spanish Natl Canc Res Ctr, Struct Biol & Biocomp Programme, Madrid, Spain
[8] Univ Salerno, Fac Med, I-84081 Baronissi, Italy
[9] Ist Ricovero Cura Carattere Sci Multimed, Genet Unit, Cardiovasc Res Inst, Sesto San Giovanni, Italy
[10] Univ Barcelona, Fundacio St Joan de Deu, Hosp St Joan de Deu, Neonatal Unit, Barcelona, Catalonia, Spain
[11] Univ Hosp Bellvitge, Internal Med Serv, Barcelona, Catalonia, Spain
[12] Univ Oviedo, Inst Univ Oncol Principado Asturias, Hosp Univ Cent Asturias, Oviedo, Spain
[13] Ctr Nacl Biotecnol, Dept Immunol & Oncol, Madrid, Spain
[14] Ctr Nacl Anal Genom, Barcelona, Catalonia, Spain
[15] Univ Copenhagen, Dept Biol, DK-1168 Copenhagen, Denmark
[16] Univ Barcelona, Sch Med, Dept Physiol Sci 2, Barcelona, Catalonia, Spain
[17] Inst Catalana Recerca & Estudis Avancats, Barcelona, Catalonia, Spain
基金
欧洲研究理事会;
关键词
epigenomics; longevity; STEM-CELLS; METHYLATION; CANCER; GENES; HYPERMETHYLATION;
D O I
10.1073/pnas.1120658109
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:10522 / 10527
页数:6
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