Widespread and tissue specific age-related DNA methylation changes in mice
Open accessAbstract
Aberrant methylation of promoter CpG islands in cancer is associated with silencing of tumor-suppressor genes, and age-dependent hypermethylation in normal appearing mucosa may be a risk factor for human colon cancer. It is not known whether this age-related DNA methylation phenomenon is specific to human tissues. We performed comprehensive DNA methylation profiling of promoter regions in aging mouse intestine using methylated CpG island amplification in combination with microarray analysis. By comparing C57BL/6 mice at 3-mo-old versus 35-mo-old for 3627 detectable autosomal genes, we found 774 (21%) that showed increased methylation and 466 (13%) that showed decreased methylation. We used pyrosequencing to quantitatively validate the microarray data and confirmed linear age-related methylation changes for all 12 genomic regions examined. We then examined 11 changed genomic loci for age-related methylation in other tissues. Of these, three of 11 showed similar changes in lung, seven of 11 changed in liver, and six of 11 changed in spleen, though to a lower degree than the changes seen in colon. There was partial conservation between age-related hypermethylation in human and mouse intestines, and Polycomb targets in embryonic stem cells were enriched among the hypermethylated genes. Our findings demonstrate a surprisingly high rate of hyper- and hypomethylation as a function of age in normal mouse small intestine tissues and a strong tissue-specificity to the process. We conclude that epigenetic deregulation is a common feature of aging in mammals.
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Dynamic changes in DNA methylation occur across tissues during aging in humans, nonhuman primates, and mice.
“it is shown that dynamic changes in DNA methylation occur across tissues during aging in humans10, nonhuman primates11, and mice12,13.”
From Integrated analysis of behavioral, epigenetic, and gut microbiome analyses in AppNL-G-F, AppNL-F, and wild type mice (2021) · cites this paper as [12]
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- Authors
- Maegawa, S., Hinkal, G., Kim, H. S., Shen, L., Zhang, L., Zhang, J., Zhang, N., Liang, S., Donehower, L. A., & Issa, J.-P. J.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Baylor College of Medicine (US)
- Venue
- Genome Research
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2010-01-27
- Volume
- 20
- Issue
- 3
- Pages
- 332-340
- ISSN
- 1088-9051 (ISSN-L)
- PMC
- PMC2840983
- OpenAlex
- W2149585679
- Cited by
- 553
- References
- 4
- Citations by year
- 2026: 7 · 2025: 20 · 2024: 33 · 2023: 35 · 2022: 36 · 2021: 23 · 2020: 32 · 2019: 42 · 2018: 26 · 2017: 36 · 2016: 33 · 2015: 51 · 2014: 43 · 2013: 38 · 2012: 38
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genome Research (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- F. M. Kirby Foundation
- James N. Kirby Foundation
- National Institutes of Health (CA-16 672, CA100632)
- National Cancer Institute (P50CA100632, CA-16672, CA105346, CA100632, R01CA098006, K25CA123344, R01CA105346, CA098006, P30CA016672)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- promoter CpG islands, tissue-specific methylation, hypermethylation, hypomethylation, colon cancer risk, embryonic stem cells
- MeSH terms
- Aging, Animals, Colonic Neoplasms, Female, Male, Neoplasms, Organ Specificity, CpG Islands, DNA Methylation, Mice
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