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Abstract
Aging is a universal biological process connecting an organism’s life history along a common thread of time. However, the proximal mechanisms which govern aging, integrate environmental signals, and ultimately determine maximum lifespan are poorly resolved. Over the last decade, age-associated variation in epigenetic modifications, including DNA methylation, has emerged as a likely mediator of environmental influences on biological aging. DNA methylation is known to respond both rapidly and persistently to environmental conditions, promote genomic stability, control aspects of gene expression, and guide developmental processes. Most interestingly, predictable changes in DNA methylation are strongly correlated with chronological age in a variety of organisms. Here, we use DNA methylation as a lens through which the fundamental aging process can be observed and a molecular context in which questions related to the modulation of life history strategies and the determination of species-specific maximum lifespans can be explored. To do this, we first develop a novel epigenetic age predictor in a model teleost species, the Japanese medaka fish (Oryzias latipes) and use this system to investigate the integration of environmental conditions into epigenetic aging and life history trajectories. We then use the same model to elucidate the role of stress hormone mediated life-stage specificity to environmental stressors. Expanding on our knowledge of the aging epigenome, we then use the mouse model (Mus musculus) to add an additional dimension to epigenetic aging by describing how the disorder of methylation patterns changes with age at a global and regional scale. In describing epigenetic disorder, we draw both similarities and contrasts to canonical epigenetic aging. Lastly, we apply our metric of epigenetic disorder to four different mammal species with maximum lifespans ranging from 3.8 to 26.7 years and test the hypothesis that the rate of epigenetic drift explains species-specific maximum lifespan and is mediated by CpG density. Overall, the work within this dissertation adds to our understanding of how DNA methylation patterns change with age and modulate aspects of biological aging at the individual and species levels.