Revisiting the genomic hypomethylation hypothesis of aging
Open accessAbstract
The genomic hypomethylation hypothesis of aging proposes that an overall decrease in global DNA methylation occurs with age, and it has been argued that the decrease in global DNA methylation could be an important factor in aging, resulting in the relaxation of gene expression regulation and abnormal gene expression. Since it was initially observed that DNA methylation decreased with age in 1974, 16 articles have been published describing the effect of age on global DNA methylation in various tissues from rodents and humans. We critically reviewed the publications on the effect of age on DNA methylation and the expression of the enzymes involved in DNA methylation to evaluate the validity of the hypomethylation hypothesis of aging. On the basis of the current scientific literature, we conclude that a decrease in the global methylation of the genome occurs in most if not all tissues/cells as an animal ages. However, age‐related changes in DNA methylation in specific regions or at specific sites in the genome occur even though the global DNA methylation does not change.
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During aging, global DNA hypomethylation is observed in many species including rat, mouse, and human.
“During aging, global DNA hypomethylation is observed in many species including rat, mouse, and human [511].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [511]
A stable epigenome is reported to contribute to longevity and cancer resistance.
“In contrast, a stable epigenome is reported to contribute to longevity and cancer resistance 51 .”
From The roles of DNA, RNA and histone methylation in ageing and cancer (2019) · cites this paper as [51]
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- Authors
- Unnikrishnan, A., Hadad, N., Masser, D. R., Jackson, J., Freeman, W. M., & Richardson, A.
- Affiliations
- University of Oklahoma Health Sciences Center (US)
- Oklahoma City VA Medical Center (US)
- Corresponding author
- Richardson, Arlan
- Venue
- Annals of the New York Academy of Sciences
- Publisher
- Wiley
- Published
- 2018-01-24
- Volume
- 1418
- Issue
- 1
- Pages
- 69-79
- ISSN
- 0077-8923 (ISSN-L)
- 1749-6632
- PMC
- PMC5934293
- OpenAlex
- W2791213438
- Cited by
- 113
- References
- 71
- Citations by year
- 2026: 11 · 2025: 15 · 2024: 25 · 2023: 15 · 2022: 15 · 2021: 8 · 2020: 9 · 2019: 9 · 2018: 5
- FWCI
- 2.76
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annals of the New York Academy of Sciences (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Oklahoma Center for the Advancement of Science and Technology (HR14‐174)
- National Institutes of Health (AG045693)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
- Keywords
- DNA methylation, aging, global DNA methylation, DNA methylation enzymes, gene expression regulation
- MeSH terms
- Aging, Animals, Enzymes, Gene Expression Regulation, Humans, DNA Methylation, Genomics, Mice, Rats
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