Distinct DNA methylomes of newborns and centenarians
Open accessAbstract
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.
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During aging, human brain DNA methylation levels gradually increase at genomic loci located at CpG islands and gene promoters, whereas intergenic CpG sites are marked with hypomethylation.
“These observations are consistent with the knowledge that during aging, human brain DNA methylation levels gradually increase (hypermethylation) at genomic loci located at CpG islands and gene promoters, whereas intergenic CpG sites are marked with hypomethylation [50, 51].”
From Sex-specific DNA methylation differences in Alzheimer’s disease pathology (2021) · cites this paper as [51]
The Results and Discussion (page not provided) report greater methylation at CpG-island promoters and lower methylation in intergenic regions in centenarian CD4+ T cells than in newborn cells. Middle-aged blood samples showed intermediate methylation at many age-associated sites. The paper does not establish this pattern in human brain, and its findings do not support an increase at gene promoters generally: CpG-poor promoters were less methylated with age. (LLM, conf=0.89)
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- Authors
- Heyn, H., Li, N., Ferreira, H. J., Moran, S., Pisano, D. G., Gomez, A., Diez, J., Sanchez-Mut, J. V., Setien, F., Carmona, F. J., Puca, A. A., Sayols, S., Pujana, M. A., Serra-Musach, J., Iglesias-Platas, I., Formiga, F., Fernandez, A. F., Fraga, M. F., Heath, S. C., Valencia, A., Gut, I. G., Wang, J., & Esteller, M.
- Affiliations
- Cancer Epigenetics and Biology Program;
- BGI Group (China) (CN)
- Centro de Neurociências e Biologia Celular (PT)
- Spanish National Cancer Research Centre (ES)
- University of Salerno (IT)
- Biomarkers and Susceptibility Unit, Spanish Biomedical Research Centre Network for Epidemiology and Public Health; Catalan Institute of Oncology, Bellvitge Biomedical Research Institute, L’Hospitalet, Barcelona, Catalonia 08908, Spain;
- Institut d'Investigació Biomédica de Bellvitge (ES)
- Neonatal Unit, Hospital Sant Joan de Déu, Fundació Sant Joan de Déu, Barcelona University, Barcelona, Catalonia, Spain;
- Internal Medicine Service, University Hospital of Bellvitge, L’Hospitalet, Barcelona, Catalonia, Spain;
- Instituto Universitario de Oncología del Principado de Asturias, Hospital Universitario Central de Asturias, Universidad de Oviedo, Oviedo, Spain;
- Universidad de Oviedo (ES)
- Centro Nacional de Análisis Genómico (ES)
- University of Copenhagen (DK)
- Institució Catalana de Recerca i Estudis Avançats (ES)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2012-06-11
- Volume
- 109
- Issue
- 26
- Pages
- 10522-10527
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3387108
- OpenAlex
- W2165101781
- Cited by
- 802
- References
- 3
- Citations by year
- 2026: 27 · 2025: 38 · 2024: 38 · 2023: 54 · 2022: 41 · 2021: 54 · 2020: 55 · 2019: 57 · 2018: 61 · 2017: 67 · 2016: 73 · 2015: 89 · 2014: 62 · 2013: 62 · 2012: 23
- FWCI
- 30.36
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Consultation of the Doctoral Thesis Database (TESEO) (Ministerio de Educación, Cultura y Deporte) (submittedVersion, cc-by-nc-nd)
- Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (submittedVersion, public-domain)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
- Keywords
- DNA methylation, epigenetic drift, centenarians, aging, neonates, CpG methylation, promoter methylation, CpG islands, tissue-specific genes
- MeSH terms
- Aged, Aged, 80 and over, Humans, Infant, Newborn, DNA Methylation
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