Author: Unnikrishnan A1, Freeman WM2, Jackson J3, Wren JD4, Porter H5, Richardson A6
Affiliation:
1Reynolds 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: archana-unnikrishnan@ouhsc.edu.
2Reynolds 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.
3Reynolds Oklahoma Center on Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
4Department 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.
5Reynolds 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.
6Reynolds 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.
Conference/Journal: Pharmacol Ther.
Date published: 2018 Nov 9
Other:
Pages: S0163-7258(18)30198-0 , Special Notes: doi: 10.1016/j.pharmthera.2018.11.001. [Epub ahead of print] , Word Count: 329
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
PMID: 30419258 DOI: 10.1016/j.pharmthera.2018.11.001
