Using DNA Methylation Data to Understand the Evolutionary Basis of Human Aging Public

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

About this Dissertation

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School	Laney Graduate School
Department	Biological and Biomedical Sciences
Subfield / Discipline	Population Biology, Ecology & Evolution
Degree	Ph.D.
Submission	Dissertation
Language	English
Research Field	Biology, Genetics Biology, Evolution and Development
Mot-clé	mutation accumulation disposable soma DNA methylation aging evolution
Committee Chair / Thesis Advisor	Conneely, Karen, Emory University
Committee Members	Epstein, Michael, Emory University Beck, Christopher, Emory University Cutler, David, Emory University Antia, Rustom, Emory University

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