Testing Two Evolutionary Theories of Human Aging with DNA Methylation Data

Robins, Chloe, McRae, Allan F., Powell, Joseph E., Wiener, Howard W., Aslibekyan, Stella, Kennedy, Elizabeth M., Absher, Devin M., Arnett, Donna K., Montgomery, Grant W., Visscher, Peter M., Cutler, David J. and Conneely, Karen N. (2017) Testing Two Evolutionary Theories of Human Aging with DNA Methylation Data. Genetics, 207 4: 1547-1560. doi:10.1534/genetics.117.300217


Author Robins, Chloe
McRae, Allan F.
Powell, Joseph E.
Wiener, Howard W.
Aslibekyan, Stella
Kennedy, Elizabeth M.
Absher, Devin M.
Arnett, Donna K.
Montgomery, Grant W.
Visscher, Peter M.
Cutler, David J.
Conneely, Karen N.
Title Testing Two Evolutionary Theories of Human Aging with DNA Methylation Data
Journal name Genetics   Check publisher's open access policy
ISSN 0016-6731
1943-2631
Publication date 2017-12-01
Year available 2017
Sub-type Article (original research)
DOI 10.1534/genetics.117.300217
Open Access Status Not yet assessed
Volume 207
Issue 4
Start page 1547
End page 1560
Total pages 14
Place of publication Bethesda, MD., United States
Publisher Genetics Society of America
Language eng
Subject 1311 Genetics
Abstract 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.
Keyword Lipid-Lowering Drugs
Epigenetic Drift
Diet Network
Natural-Selection
Genetic-Variation
Age
Senescence
Genome
Expression
Longevity
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID NRSA 0000030423
RO1 HL104135
613608
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Queensland Brain Institute Publications
Institute for Molecular Bioscience - Publications
 
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Created: Sat, 16 Dec 2017, 23:09:33 EST