Signatures of Aging and Environment in the DNA Methylome of Rhesus Macaques
| dc.contributor.advisor | Sterner, Kirstin | |
| dc.contributor.author | Goldman, Elisabeth | |
| dc.date.accessioned | 2022-10-04T20:40:49Z | |
| dc.date.issued | 2022-10-04 | |
| dc.description.abstract | While the link between aging and metabolic function is well recognized, little is known about how variables like diet are able to drive variation in health and longevity through interaction with molecular mechanisms of aging. Because aging does not occur uniformly throughout the body, tissue-specific analyses are necessary to elucidate patterns of age-related decline in organs with distinct physiological roles. Multi-tissue clocks have gained popularity in human clinical and biomedical research, but these models provide just one estimate of systemic health and cannot indicate where early, sub-clinical signs of disease may be starting to subtly manifest. Here, I took a targeted, tissue-specific approach and constructed two generalizable epigenetic clock models using genome-wide methylation data generated from blood (n=563) and liver (n=96) samples from rhesus macaques. I tested the blood-based model in an independent group of female rhesus macaques (n=43) as well as a group of wild yellow baboons (n=271) and found it predicted age with high accuracy in both populations. Next, I applied the liver clock to test whether long-term dietary restriction, a known pro-longevity intervention, delayed the pace of epigenetic aging in 63 rhesus macaques from a 33-year study conducted at the National Institute on Aging (NIA). Monkeys entered the study at one of three developmental time points. I found that males who entered the diet study at older ages (>15 years) reaped the greatest longevity benefit but did not show slower rates of epigenetic aging. Both males and females who started the restricted diet as juveniles showed slower rates of epigenetic aging but saw no improvement in life expectancy, suggesting the clock may track trade-offs in energy allocation and could, in later life, become decoupled from an individual's risk of mortality. Finally, I found that all individuals in the dietary restriction study showed significantly less age-related loss of methylation compared to age-matched controls from the original liver dataset, suggesting diet-modification effectively delays age-related deterioration in the methylome. This dissertation includes previously unpublished co-authored material. | en_US |
| dc.description.embargo | 2023-08-09 | |
| dc.identifier.uri | https://hdl.handle.net/1794/27644 | |
| dc.language.iso | en_US | |
| dc.publisher | University of Oregon | |
| dc.rights | All Rights Reserved. | |
| dc.subject | Aging | en_US |
| dc.subject | Bioinformatics | en_US |
| dc.subject | Epigenetic clock | en_US |
| dc.subject | Epigenomics | en_US |
| dc.subject | Methylation | en_US |
| dc.subject | Primates | en_US |
| dc.title | Signatures of Aging and Environment in the DNA Methylome of Rhesus Macaques | |
| dc.type | Electronic Thesis or Dissertation | |
| thesis.degree.discipline | Department of Anthropology | |
| thesis.degree.grantor | University of Oregon | |
| thesis.degree.level | doctoral | |
| thesis.degree.name | Ph.D. |
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