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PMID: 30419258 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Review

The role of DNA methylation in epigenetics of aging.

Pharmacology & therapeutics ·Vol. 195 ·2019-00-00 ·Pages 172-185

Unnikrishnan A, Freeman WM, Jackson J, Wren JD, Porter H, Richardson A

Abstract

Recent research suggests that epigenetics, especially DNA methylation, plays a mechanistic role in aging. Epigenetic clocks, which measure changes in a few hundred specific CpG sites, can accurately predict chronological age in a variety of species, including humans. These clocks are currently the best biomarkers for predicting mortality in humans. Additionally, several studies have characterized the effects of aging across the methylome in a wide variety of tissues from humans and mice. A small fraction (~2%) of the CpG sites show age-related changes, either hypermethylation or hypomethylation with aging. Evaluation of non-CpG site methylation has only been examined in a few studies, with about ~0.5% of these sites showing a change with age. Therefore, while only a small fraction of cytosines in the genome show changes in DNA methylation with age, this represents 2 to 3 million cytosines in the genome. Importantly, the only study to compare the effect of aging on DNA methylation in male and female mice and humans found that >95% of the age-related changes in DNA methylation in the hippocampus were sexually divergent, i.e., the methylation did not differ between males and females at young age but age-related changes occurred in one sex but not the other. The age-related changes in DNA methylation tend to be enriched and under-represented in specific genomic contexts, with some commonalities between tissues and species that require further investigation. The strongest evidence that the age-related changes in DNA methylation play a role in aging comes from studies of anti-aging interventions (e.g., caloric restriction, dwarfism, and rapamycin treatment) in mice. These anti-aging interventions deaccelerate the epigenetic clocks and reverse/prevent 20 to 40% of the age-related changes in DNA methylation. It will be important in the future to demonstrate that at least some of the age-related changes in DNA methylation directly lead to alterations in the transcriptome of cells/tissues that could potentially contribute to aging.

Keywords
5-hydroxymethyl cytosine 5-methyl cytosine Aging Caloric restriction DNA methylation Epigenetic clocks Epigenetics Gene Expression
MeSH Terms
Aging/genetics Animals DNA Methylation Epigenesis, Genetic Epigenomics Humans
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Unnikrishnan Archana
Reynolds Oklahoma Center on Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. Electronic address: [email protected].
Freeman Willard M
Reynolds Oklahoma Center on Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Oklahoma City VA Medical Center, Oklahoma City, OK, USA.
Jackson Jordan
Reynolds Oklahoma Center on Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Wren Jonathan D
Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Department of Biochemistry & Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Arthritis & Clinical Immunology Program, Division of Genomics and Data Sciences, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
Porter Hunter
Reynolds Oklahoma Center on Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Richardson Arlan
Reynolds Oklahoma Center on Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Oklahoma City VA Medical Center, Oklahoma City, OK, USA.
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Article Info
Journal
Pharmacology & therapeutics
Abbr.
Pharmacol Ther
ISSN
1879-016X
DOI
10.1016/j.pharmthera.2018.11.001
Email
[email protected]
Published
2019-00-00
Epub
2018-00-09
Pages
172-185
Language
English
Region
England
NLM ID
7905840
PMCID
PMC6397707
Subset
IM
Grants
NEI NIH HHS · R21 EY024520 · United States
NEI NIH HHS · R01 EY021716 · United States
NIA NIH HHS · T32 AG052363 · United States
BLRD VA · I01 BX003906 · United States
NIA NIH HHS · R01 AG045693 · United States
NIA NIH HHS · P30 AG050911 · United States
NIA NIH HHS · R01 AG059430 · United States
External Links
PubMed source DOI: 10.1016/j.pharmthera.2018.11.001 PMC Full Text View journal details
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