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.
|Number of pages||14|
|State||Published - Dec 2017|
Bibliographical noteFunding Information:
The authors thank Benjamin Barwick for helpful discussions and for sharing his annotation and code for the gene ontology analysis. This research was supported by grants from the National Institute on Aging (NRSA 0000030423 to C.R.), the National Heart, Lung, and Blood Institute (RO1 HL104135 to D.K.A. and D.M.A.), and the National Health and Medical Research Council (grants 613608, 1046880, and 1078037 to P.M.V.; fellowship 1010374 and grant 1083656 to A.F.M.; and fellowship 110759 to J.E.P.). The authors have no conflicts of interest to declare.
© 2017 by the Genetics Society of America.
- DNA methylation
- Disposable soma
- Mutation accumulation
ASJC Scopus subject areas