The role of DNA methylation in epigenetics of aging

被引：230

作者：

Unnikrishnan, Archana ^{[1
,2
]}

Freeman, Willard M. ^{[1
,3
,5
,6
]}

Jackson, Jordan ^{[1
]}

Wren, Jonathan D. ^{[2
,4
,5
,7
]}

Porter, Hunter ^{[1
,5
]}

Richardson, Arlan ^{[1
,2
,6
]}

机构：

[1] Univ Oklahoma, Hlth Sci Ctr, Reynolds Oklahoma Ctr Aging, Oklahoma City, OK USA

[2] Univ Oklahoma, Hlth Sci Ctr, Dept Geriatr Med, Oklahoma City, OK 73104 USA

[3] Univ Oklahoma, Hlth Sci Ctr, Dept Physiol, Oklahoma City, OK USA

[4] Univ Oklahoma, Hlth Sci Ctr, Dept Biochem & Mol Biol, Oklahoma City, OK 73190 USA

[5] Univ Oklahoma, Hlth Sci Ctr, Oklahoma Ctr Neurosci, Oklahoma City, OK USA

[6] Oklahoma City VA Med Ctr, Oklahoma City, OK USA

[7] Oklahoma Med Res Fdn, Div Genom & Data Sci, Arthrit & Clin Immunol Program, 825 NE 13th St, Oklahoma City, OK 73104 USA

来源：

PHARMACOLOGY & THERAPEUTICS | 2019年 / 195卷

关键词：

DNA methylation; Epigenetics; Aging; Caloric restriction; 5-methyl cytosine; 5-hydroxymethyl cytosine; Epigenetic clocks; Gene Expression; LIFE-SPAN EXTENSION; TET PROTEINS; BIOLOGICAL AGE; LONGEVITY; MICE; 5-HYDROXYMETHYLCYTOSINE; RESTRICTION; EXPRESSION; GROWTH; GENES;

D O I：

10.1016/j.pharmthera.2018.11.001

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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 (similar to 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 similar to 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 rapamydn 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. (C) 2018 The Authors. Published by Elsevier Inc.

引用

页码：172 / 185

页数：14

共 112 条

[1]

ASDELL SA, 1967, J REPROD FERTIL, V14, P113, DOI 10.1530/jrf.0.0140113

[2] Mice expressing an error-prone DNA polymerase in mitochondria display elevated replication pausing and chromosomal breakage at fragile sites of mitochondrial DNA [J].

Bailey, Laura J. ;

Cluett, Tricia J. ;

Reyes, Aurelio ;

Prolla, Tom A. ;

Poulton, Joanna ;

Leeuwenburgh, Christiaan ;

Holt, Ian J. .

NUCLEIC ACIDS RESEARCH, 2009, 37 (07) :2327-2335

[3] DNA methylation patterns and epigenetic memory [J].

Bird, A .

GENES & DEVELOPMENT, 2002, 16 (01) :6-21

[4] Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice [J].

Bitto, Alessandro ;

Ito, Takashi K. ;

Pineda, Victor V. ;

LeTexier, Nicolas J. ;

Huang, Heather Z. ;

Sutlief, Elissa ;

Tung, Herman ;

Vizzini, Nicholas ;

Chen, Belle ;

Smith, Kaleb ;

Meza, Daniel ;

Yajima, Masanao ;

Beyer, Richard P. ;

Kerr, Kathleen F. ;

Davis, Daniel J. ;

Gillespie, Catherine H. ;

Snyder, Jessica M. ;

Treuting, Piper M. ;

Kaeberlein, Matt .

ELIFE, 2016, 5

[5] Telomere dynamics rather than age predict life expectancy in the wild [J].

Bize, Pierre ;

Criscuolo, Francois ;

Metcalfe, Neil B. ;

Nasir, Lubna ;

Monaghan, Pat .

PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, 2009, 276 (1662) :1679-1683

[6] Intra-individual change over time in DNA methylation with familial clustering [J].

Bjornsson, Hans T. ;

Sigurdsson, Martin I. ;

Fallin, M. Daniele ;

Irizarry, Rafael A. ;

Aspelund, Thor ;

Cui, Hengmi ;

Yu, Wenqiang ;

Rongione, Michael A. ;

Ekstrom, Tomas J. ;

Harris, Tamara B. ;

Launer, Lenore J. ;

Eiriksdottir, Gudny ;

Leppert, Mark F. ;

Sapienza, Carmen ;

Gudnason, Vilmundur ;

Feinberg, Andrew P. .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2008, 299 (24) :2877-2883

[7] Epigenetic Predictor of Age [J].

Bocklandt, Sven ;

Lin, Wen ;

Sehl, Mary E. ;

Sanchez, Francisco J. ;

Sinsheimer, Janet S. ;

Horvath, Steve ;

Vilain, Eric .

PLOS ONE, 2011, 6 (06)

[8] Epigenetic regulatory functions of DNA modifications: 5-methylcytosine and beyond [J].

Breiling, Achim ;

Lyko, Frank .

EPIGENETICS & CHROMATIN, 2015, 8

[9] Frailty is associated with the epigenetic clock but not with telomere length in a German cohort [J].

Breitling, Lutz Philipp ;

Saum, Kai-Uwe ;

Perna, Laura ;

Schoettker, Ben ;

Holleczek, Bernd ;

Brenner, Hermann .

CLINICAL EPIGENETICS, 2016, 8 :1-8

[10] Dwarf mice and the ageing process [J].

BrownBorg, HM ;

Borg, KE ;

Meliska, CJ ;

Bartke, A .

NATURE, 1996, 384 (6604) :33-33

← 1 2 3 4 5 6 7 8 9 10 →