Aging and epigenetic drift: a vicious cycle
Open accessAbstract
The term epigenetics refers to stable patterns of gene expression that are seen during differentiation or X chromosome inactivation and are not dependent on dynamic changes in coding DNA. These gene expression states are encoded in the epigenome - a collection of marks on DNA or on histone tails that are established during embryogenesis. Genome-wide studies in aging cells and tissues have uncovered stochastic DNA methylation drift (gradual increases or decreases at specific loci) that reflects imperfect maintenance of epigenetic marks. Drift creates epigenetic mosaicism in aging stem cells that could potentially restrict their plasticity and worsen phenotypes such as stem cell exhaustion and focal proliferative defects that can lead to cancer.
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Cytosine methylation tends to decrease slowly with aging over large, gene-poor regions enriched for heterochromatin and repetitive sequences, whereas methylation at gene-associated CpG islands can increase or decrease more dramatically with tissue-specific effects.
“Cytosine methylation tends to decrease slowly with aging over large, gene-poor regions of the genome that are enriched for heterochromatin and repetitive sequences, whereas methylation at gene-associated CpG islands can increase or decrease more dramatically, with pronounced tissue-specific effects70, 71.”
From The role of retrotransposable elements in ageing and age-associated diseases (2021) · cites this paper as [70]
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- Authors
- Issa, J.-P.
- Affiliations
- Temple University (US)
- Corresponding author
- Issa, Jean-Pierre
- ORCID
- Issa, Jean-Pierre
- Venue
- Journal of Clinical Investigation
- Published
- 2014-01-02
- Volume
- 124
- Issue
- 1
- Pages
- 24-29
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC3871228
- OpenAlex
- W2113296450
- Cited by
- 419
- References
- 87
- Citations by year
- 2026: 38 · 2025: 20 · 2024: 27 · 2023: 21 · 2022: 41 · 2021: 32 · 2020: 36 · 2019: 23 · 2018: 45 · 2017: 39 · 2016: 35 · 2015: 42 · 2014: 20
- FWCI
- 4.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ellison Medical Foundation
- F. M. Kirby Foundation
- Temple University
- James N. Kirby Foundation
- National Institutes of Health
- National Cancer Institute (P50CA100632, CA158112, R01CA158112)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- aging, epigenetic drift, stem cell aging, stem cell exhaustion, histone modifications, cancer risk, cellular heterogeneity
- MeSH terms
- Aging, Animals, Histones, Humans, Neoplasms, Protein Processing, Post-Translational, DNA Methylation, Epigenesis, Genetic
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