The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Cross-sectional and longitudinal changes in DNA methylation with age: an epigenome-wide analysis revealing over 60 novel age-associated CpG sites
Open accessAbstract
Understanding the role of epigenetic modifications, e.g. DNA methylation, in the process of aging requires the characterization of methylation patterns in large cohorts. We analysed >480 000 CpG sites using Infinium HumanMethylation450 BeadChip (Illumina) in whole blood DNA of 965 participants of a population-based cohort study aged between 50 and 75 years. In an exploratory analysis in 400 individuals, 200 CpG sites with the highest Spearman correlation coefficients for the association between methylation and age were identified. Of these 200 CpGs, 162 were significantly associated with age, which was verified in an independent cohort of 498 individuals using mixed linear regression models adjusted for gender, smoking behaviour, age-related diseases and random batch effect and corrected for multiple testing by Bonferroni. In another independent cohort of 67 individuals without history of major age-related diseases and with a follow-up of 8 years, we observed a gain in methylation at 96% (52%, significant) of the positively age-associated CpGs and a loss at all (89%, significant) of the negatively age-associated CpGs in each individual while getting 8 years older. A regression model for age prediction based on 17 CpGs as predicting variables explained 71% of the variance in age with an average accuracy of 2.6 years. In comparison with cord blood samples obtained from the Ulm Birth Cohort Study, we observed a more than 2-fold change in mean methylation levels from birth to older age at 86 CpGs. We were able to identify 65 novel CpG sites with significant association of methylation with age.
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Cites
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources
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Functions of DNA methylation: islands, start sites, gene bodies and beyond
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Genome-wide methylation profiles reveal quantitative views of human aging rates
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High density DNA methylation array with single CpG site resolution
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Validation of a DNA methylation microarray for 450,000 CpG sites in the human genome
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“Of the 155 significantly age-associated CpG sites, 70% were located in CpG islands, 19% in CpG island shores or shelves and 11% outside CpG islands (‘open sea’), whereas of all CpG sites on the Infinum HumanMethylation450 BeadChip, 31% were located in CpG islands, 33% in island shores or shelves and 36% in ‘open sea’…”
BackgroundThe aging of the immune system
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Distinct DNA methylomes of newborns and centenarians
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“epigenetic modification in humans and have been associated with age-related diseases such as diabetes mellitus (type 2) (1), cardiovascular disease (2,3) and cancer (4,5).”
BackgroundMethod
Cited by
DNA methylation-based biomarkers and the epigenetic clock theory of ageing
Horvath, S., & Raj, K. (2018) · Nature Reviews Genetics · doi:10.1038/s41576-018-0004-3 · Cited by 3,095
DNA methylation and healthy human aging
Jones, M. J., Goodman, S. J., & Kobor, M. S. (2015) · Aging Cell · doi:10.1111/acel.12349 · Cited by 928
Epigenetic modulators, modifiers and mediators in cancer aetiology and progression
Feinberg, A. P., Koldobskiy, M. A., & Göndör, A. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2016.13 · Cited by 841
Perna, L., Zhang, Y., Mons, U., Holleczek, B., Saum, K.-U., & Brenner, H. (2016) · Clinical Epigenetics · doi:10.1186/s13148-016-0228-z · Cited by 572
Self-citationDNA methylation signatures in peripheral blood strongly predict all-cause mortality
Zhang, Y., Wilson, R., Heiss, J., Breitling, L. P., Saum, K.-U., Schöttker, B., Holleczek, B., Waldenberger, M., Peters, A., & Brenner, H. (2017) · Nature Communications · doi:10.1038/ncomms14617 · Cited by 382
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Metadata
- Authors
- Florath, I., Butterbach, K., Muller, H., Bewerunge-Hudler, M., & Brenner, H.
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-10-26
- Volume
- 23
- Issue
- 5
- Pages
- 1186-1201
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2168880641
- Cited by
- 335
- References
- 9
- FWCI
- 12.78
- Type
- journal article
- Language
- en
- Open access
- green
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- Florath, I., Butterbach, K., Muller, H., Bewerunge-Hudler, M., & Brenner, H. (2014). Cross-sectional and longitudinal changes in DNA methylation with age: an epigenome-wide analysis revealing over 60 novel age-associated CpG sites. Human Molecular Genetics. https://doi.org/10.1093/hmg/ddt531
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