Testing Two Evolutionary Theories of Human Aging with DNA Methylation Data

被引：9

作者：

Robins, Chloe ^{[1
,2
]}

McRae, Allan F. ^{[3
,4
]}

Powell, Joseph E. ^{[3
,4
]}

Wiener, Howard W. ^{[5
]}

Aslibekyan, Stella ^{[5
]}

Kennedy, Elizabeth M. ^{[1
]}

Absher, Devin M. ^{[6
]}

Arnett, Donna K. ^{[7
]}

Montgomery, Grant W. ^{[3
]}

Visscher, Peter M. ^{[3
,4
]}

Cutler, David J. ^{[1
]}

Conneely, Karen N. ^{[1
]}

机构：

[1] Emory Univ, Sch Med, Dept Human Genet, 615 Michael St NE, Atlanta, GA 30322 USA

[2] Emory Univ, Laney Grad Sch, Grad Program Populat Biol Ecol & Evolut, Atlanta, GA 30322 USA

[3] Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4072, Australia

[4] Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia

[5] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL 35205 USA

[6] HudsonAlpha Inst Biotechnol, Huntsville, AL 35806 USA

[7] Univ Kentucky, Coll Publ Hlth, Lexington, KY 40536 USA

来源：

GENETICS | 2017年 / 207卷 / 04期

基金：

英国医学研究理事会;

关键词：

aging; evolution; DNA methylation; mutation accumulation; disposable soma; LIPID-LOWERING DRUGS; EPIGENETIC DRIFT; GENETIC-VARIATION; AGE; SENESCENCE; EXPRESSION; LONGEVITY; BLOOD;

D O I：

10.1534/genetics.117.300217

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

The evolutionary theories of mutation accumulation (MA) and disposable soma (DS) provide possible explanations for the existence of human aging. To better understand the relative importance of these theories, we devised a test to identify MA-and DS-consistent sites across the genome using familial DNA methylation data. Two key characteristics of DNA methylation allowed us to do so. First, DNA methylation exhibits distinct and widespread changes with age, with numerous age-differentially-methylated sites observed across the genome. Second, many sites show heritable DNA methylation patterns within families. We extended heritability predictions of MA and DS to DNA methylation, predicting that MA-consistent age-differentially-methylated sites will show increasing heritability with age, while DS-consistent sites will show the opposite. Variance components models were used to test for changing heritability of methylation with age at 48,601 age-differentially-methylated sites across the genome in 610 individuals from 176 families. Of these, 102 sites showed significant MA-consistent increases in heritability with age, while 2266 showed significant DS-consistent decreases in heritability. These results suggest that both MA and DS play a role in explaining aging and aging-related changes, and that while the majority of DNA methylation changes observed in aging are consistent with epigenetic drift, targeted changes exist and may mediate effects of aging-related genes.

引用

页码：1547 / 1560

页数：14