Epigenetics and aging: the targets and the marks
Abstract
'Aging epigenetics' is an emerging field that promises exciting revelations in the near future. Here we focus on the functional and biological significance of the epigenetic alterations that accumulate during aging and are important in tumorigenesis. Paradigmatic examples are provided by the global loss of DNA methylation in aging and cancer and by the promoter hypermethylation of genes with a dual role in tumor suppression and progeria, such as the Werner syndrome (WRN) and lamin A/C genes. Another twist is provided by sirtuins, a family of NAD-dependent deacetylases that act on Lys16 of histone H4, which are emerging as a link between cellular transformation and lifespan.
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Global hypomethylation of DNA may lead to genomic instability.
“It is recognized that epigenetic stability is proportional related to DNA methylation, as global hypomethylation of DNA may lead to genomic instability [179, 180].”
From Air pollution and children’s health—a review of adverse effects associated with prenatal exposure from fine to ultrafine particulate matter (2021) · cites this paper as [179]
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BackgroundResultLong noncoding RNAs (lncRNAs) and the molecular hallmarks of aging
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“Histone modifications The most common epigenetic alterations during aging and senescence include enhanced histone H4K16 acetylation, H4K20 trimethylation and H3K4 trimethylation, and decreased histone H3K9 methylation and H3K27 trimethylation [66, 67, 68, 69].”
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“DNA methylation is an epigenetic modification of DNA that has an important role in embryonic development, tumorigenesis, aging, and other diseases [60–62].”
BackgroundZbieć-Piekarska, R., Spólnicka, M., Kupiec, T., Makowska, Ż., Spas, A., Parys-Proszek, A., Kucharczyk, K., Płoski, R., & Branicki, W. (2015) · Forensic Science International: Genetics · doi:10.1016/j.fsigen.2014.10.002 · Cited by 203 · see citing works
“[12].”
Chromatin structure as a mediator of aging
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“Aging is accompanied by gross changes in DNA methylation, but this will not be discussed further here as this subject has been covered comprehensively in recent reviews [9,10].”
BackgroundGenome-wide screen of promoter methylation identifies novel markers in melanomaPreprint
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“Epigenetic change can be stochastic [95] or internally orchestrated as part of aging [96].”
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“Tissues and cells of aging organisms also show age-associated changes in histone chromatin marks such as increased histone H4 lysine(K)16 acetylation, H4K20 trimethylation, or H3K4 trimethylation, as well as decreased H3K9 methylation [73-75].”
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“increasing heterogeneity within a cell population and can also contribute to tumor development (Fraga and Esteller, 2007).”
InfluentialAge influences DNA methylation and gene expression of COX7A1 in human skeletal muscle.
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“Our findings are supported by previous results showing accumulation of epigenetic alterations with ageing [47–49].”
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BackgroundAging and reprogramming: a two-way street
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“Reported age-related changes to DNA methylation have typically included a general loss of methylation, or hypomethylation, across the genome (6,8,9), accompanied by site-specific hypermethylation at several gene promoters (10,11).”
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“SIRT1 binds directly to one or more constituents in the chromatin complex, resulting in structural reorganization, and therefore has the ability to establish silent chromatin domains (24, 79).”
Signaling networks determining life span
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“Several well-characterized histone modifications have been associated with aging; these modifications include increased histone H4K16 acetylation, H4K20 trimethylation, or H3K4 trimethylation, and decreased H3K9 methylation or H3K27 trimethylation (135).”
BackgroundA genome-wide CRISPR-based screen identifies KAT7 as a driver of cellular senescence
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“Age-related changes in DNA methylation have been reported, with a general trend toward a decrease in methylation level with aging (48).”
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BackgroundNature or nurture: Let food be your epigenetic medicine in chronic inflammatory disorders
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“which accumulate during life following exposure to different environmental conditions [6-8].”
BackgroundInfluentialConcordant and discordant DNA methylation signatures of aging in human blood and brain
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“Epigenetic aging consists principally of two distinct types of changes, termed ‘epigenetic drift’ and the ‘epigenetic clock’ [21-24].”
BackgroundIdentification of body fluid-specific DNA methylation markers for use in forensic science.
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“DNA methylation changes during aging [43].”
DAMPs, ageing, and cancer: The ‘DAMP Hypothesis’
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“, 2008) has been found in a variety of age-related diseases (Fraga et al., 2005; Fraga and Esteller, 2007), but little information is available on changes in promoter DNA methylation patterns during normal lens aging and ARCs (Palsamy et al.”
Early-Life Stress Reduces DNA Methylation of the Pomc Gene in Male Mice
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“differences in DNA methylation profile have been observed in aged monozygotic twins with a history of non-shared environments [125–127].”
BackgroundDynamic DNA methylation during aging: A "prophet" of age-related outcomes
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Specific Age-Associated DNA Methylation Changes in Human Dermal Fibroblasts
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“However, a number of specific loci become hyper-methylated during aging, such as the INK4A/ARF/ INK4b locus, the ribosomal gene cluster, estrogen receptor (ER), runt-related transcription factor 3 (RUNX3), insulin growth factor II (IGF2), E-cadherin, c-fos and others [1,10–13].”
BackgroundHistone Modifications in Senescence-Associated Resistance to Apoptosis by Oxidative Stress
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“Chromatin structure is important in regulating gene expression; it is under dynamic changes throughout life span [11].”
BackgroundInfluential
- Authors
- Fraga, M. F., & Esteller, M.
- Affiliations
- Spanish National Cancer Research Centre (ES)
- Corresponding author
- Esteller, Manel
- Venue
- Trends in Genetics
- Publisher
- Elsevier BV
- Published
- 2007-08
- Volume
- 23
- Issue
- 8
- Pages
- 413-418
- ISSN
- 0168-9525 (ISSN-L)
- OpenAlex
- W1990916340
- Cited by
- 690
- References
- 75
- Citations by year
- 2026: 11 · 2025: 23 · 2024: 19 · 2023: 31 · 2022: 29 · 2021: 30 · 2020: 49 · 2019: 52 · 2018: 43 · 2017: 30 · 2016: 32 · 2015: 46 · 2014: 43 · 2013: 48 · 2012: 47
- FWCI
- 3.14
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Trends in Genetics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- DNA methylation loss, promoter hypermethylation, tumor suppression genes, Hutchinson-Gilford progeria syndrome, Werner syndrome, lamin A/C, sirtuins, cell transformation, lifespan, carcinogenesis
- MeSH terms
- Animals, Histones, Humans, Models, Biological, Cellular Senescence, DNA Methylation, Gene Silencing, Epigenesis, Genetic
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