Distinct DNA methylomes of newborns and centenarians.
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.
Cancer Epigenetics and Biology Program, Spanish Biomedical Research Centre Network for Epidemiology and Public Health, Catalan Institute of Oncology, Bellvitge Biomedical Research Institute, L’Hospitalet, Barcelona, Catalonia 08908, Spain.
Holger
H
Heyn
Ning
N
Li
Humberto J
HJ
Ferreira
Sebastian
S
Moran
David G
DG
Pisano
Antonio
A
Gomez
Javier
J
Diez
Jose V
JV
Sanchez-Mut
Fernando
F
Setien
F Javier
FJ
Carmona
Annibale A
AA
Puca
Sergi
S
Sayols
Miguel A
MA
Pujana
Jordi
J
Serra-Musach
Isabel
I
Iglesias-Platas
Francesc
F
Formiga
Agustin F
AF
Fernandez
Mario F
MF
Fraga
Simon C
SC
Heath
Alfonso
A
Valencia
Ivo G
IG
Gut
Jun
J
Wang
Manel
M
Esteller
D000368:Aged; D000369:Aged, 80 and over; D019175:DNA Methylation; D006801:Humans; D007231:Infant, Newborn