The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Continuous Aging of the Human DNA Methylome Throughout the Human Lifespan
Open accessAbstract
DNA methylation plays an important role in development of disease and the process of aging. In this study we examine DNA methylation at 476,366 sites throughout the genome of white blood cells from a population cohort (N = 421) ranging in age from 14 to 94 years old. Age affects DNA methylation at almost one third (29%) of the sites (Bonferroni adjusted P-value <0.05), of which 60.5% becomes hypomethylated and 39.5% hypermethylated with increasing age. DNA methylation sites that are located within CpG islands (CGIs) more often become hypermethylated compared to sites outside an island. CpG sites in promoters are more unaffected by age, whereas sites in enhancers more often becomes hypo- or hypermethylated. Hypermethylated sites are overrepresented among genes that are involved in DNA binding, transcription regulation, processes of anatomical structure and developmental process and cortex neuron differentiation (P-value down to P = 9.14*10(-67)). By contrast, hypomethylated sites are not strongly overrepresented among any biological function or process. Our results indicate that the 23% of the variation in DNA methylation is attributed chronological age, and that hypermethylation is more site-specific than hypomethylation. It appears that the change in DNA methylation partly overlap with regions that change histone modifications with age, indicating an interaction between the two major epigenetic mechanisms. Epigenetic modifications and change in gene expression over time most likely reflects the natural process of aging and variation between individuals might contribute to the development of age-related phenotypes and diseases such as type II diabetes, autoimmune and cardiovascular disease.
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Cites
GOrilla: a tool for discovery and visualization of enriched GO terms in ranked gene lists
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Mapping and analysis of chromatin state dynamics in nine human cell types
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Linking DNA methylation and histone modification: patterns and paradigms
Cedar, H., & Bergman, Y. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2540 · Cited by 2,267 · cited 1×
“The fact that the average gene expression level decrease by age and that decreased levels of DNMT1 and other enzymes has been shown to result in genome-wide loss of CpG methylation [24], support our results of the larger number and less site specificity of hypomethylation.”
ResultStability and flexibility of epigenetic gene regulation in mammalian development
Reik, W. (2007) · Nature · doi:10.1038/nature05918 · Cited by 1,963 · cited 1×
“Even small changes in the methylation of a promoter region can introduce stable changes in gene expression, leading to silencing of a gene [2,3].”
BackgroundHigh density DNA methylation array with single CpG site resolution
Bibikova, M., Barnes, B., Tsan, C., Ho, V., Klotzle, B., Le, J. M., Delano, D., Zhang, L., Schroth, G. P., Gunderson, K. L., et al. (2011) · Genomics · doi:10.1016/j.ygeno.2011.07.007 · Cited by 1,727
Distinct DNA methylomes of newborns and centenarians
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., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1120658109 · Cited by 802
Abundant quantitative trait loci exist for DNA methylation and gene expression in human brain
Gibbs, J. R., van der Brug, M. P., Hernandez, D. G., Traynor, B. J., Nalls, M. A., Lai, S.-L., Arepalli, S., Dillman, A., Rafferty, I. P., Troncoso, J., et al. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1000952 · Cited by 769
Cheung, I., Shulha, H. P., Jiang, Y., Matevossian, A., Wang, J., Weng, Z., & Akbarian, S. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1001702107 · Cited by 235
Histone methylation makes its mark on longevity
Han, S., & Brunet, A. (2012) · Trends in Cell Biology · doi:10.1016/j.tcb.2011.11.001 · Cited by 204
Cited by
Accounting for cellular heterogeneity is critical in epigenome-wide association studies
Jaffe, A. E., & Irizarry, R. A. (2014) · Genome Biology · doi:10.1186/gb-2014-15-2-r31 · Cited by 1,067
Epigenetic clock analysis of diet, exercise, education, and lifestyle factors
Quach, A., Levine, M. E., Tanaka, T., Lu, A. T., Chen, B. H., Ferrucci, L., Ritz, B., Bandinelli, S., Neuhouser, M. L., Beasley, J. M., et al. (2017) · Aging · doi:10.18632/aging.101168 · Cited by 801
An epigenetic clock analysis of race/ethnicity, sex, and coronary heart disease
Horvath, S., Gurven, M., Levine, M. E., Trumble, B. C., Kaplan, H., Allayee, H., Ritz, B. R., Chen, B., Lu, A. T., Rickabaugh, T. M., et al. (2016) · Genome Biology · doi:10.1186/s13059-016-1030-0 · Cited by 733
HIV-1 infection accelerates age according to the epigenetic clock
Horvath, S., & Levine, A. J. (2015) · Journal of Infectious Diseases · doi:10.1093/infdis/jiv277 · Cited by 556
Development of a forensically useful age prediction method based on DNA methylation analysis
Zbieć-Piekarska, R., Spólnicka, M., Kupiec, T., Parys-Proszek, A., Makowska, Ż., Pałeczka, A., Kucharczyk, K., Płoski, R., & Branicki, W. (2015) · Forensic Science International: Genetics · doi:10.1016/j.fsigen.2015.05.001 · Cited by 354
Metadata
- Authors
- Johansson, Å., Enroth, S., & Gyllensten, U.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-06-27
- Volume
- 8
- Issue
- 6
- Pages
- e67378
- ISSN
- 1932-6203 (ISSN-L)
- OpenAlex
- W1996968784
- Cited by
- 380
- References
- 9
- FWCI
- 12.37
- Type
- journal article
- Language
- en
- Open access
- gold
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