Using DNA Methylation Data to Understand the Evolutionary Basis of Human Aging Open Access
Chloe Robins (Spring 2018)
Abstract
The evolutionary basis of human biological aging is not yet well understood. The evolutionary theories of 1) mutation accumulation, 2) antagonistic pleiotropy, and 3) disposable soma provide possible explanations for existence and evolution of aging. These three theories are not mutually exclusive, and it is likely that all three play some role in explaining how and why humans age. My dissertation work increases our understanding of human aging by testing predictions of evolutionary models in new ways. After reviewing the assumptions, predictions, and past empirical tests of each theory, I suggested the novel use of DNA methylation data to test previously unexplored theory predictions related to aging as a lifelong process. DNA methylation patterns are known to be highly dynamic throughout life and have recently been proposed as a biomarker of aging. Using DNA methylation data, I specifically tested: 1) whether the heritability of DNA methylation is consistent with disposable soma or mutation accumulation models; and 2) whether DNA methylation data support a stochastic aging process implied by the disposable soma model. The results of both tests suggest that most age-related DNA methylation changes are consistent with the disposable soma model of aging and may result from random environmental insults and methylation maintenance and repair errors, while a small number of aging-related changes are consistent with the mutation accumulation model and may be targeted to mediate the deleterious age-specific effects of aging genes. This indicates that both the mutation accumulation and disposable soma models play a role in explaining aging and aging-related changes, but that disposable soma is more important in understanding the age-related changes of DNA methylation.
Table of Contents
Chapter 1: Introduction....................................................................................................................................1
REFERENCES....................................................................................................................................................3
Chapter 2: Testing evolutionary models of senescence: traditional approahces and future directions.............................................................................................................................................................4
TABLES..............................................................................................................................................................30
FIGURES............................................................................................................................................................31
REFERENCES...................................................................................................................................................33
Chapter 3: Testing two evolutionary theories of human aging with DNA methylation data....................39
TABLES.............................................................................................................................................................70
FIGURES...........................................................................................................................................................71
REFERENCES...................................................................................................................................................77
SUPPLEMENTARY MATERIAL.....................................................................................................................81
Chapter 4: Testing a stochastic model of epigenetic drift against longitudinal DNA methylation data....................................................................................................................................................................89
TABLES...........................................................................................................................................................112
FIGURES.........................................................................................................................................................113
REFERENCES.................................................................................................................................................117
SUPPLEMENTARY MATERIAL...................................................................................................................119
Chapter 5: Conclusions.................................................................................................................................129
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