An Exploration of the Biology Underlying Epigenetic Clocks

Skvir, Nicholas John

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Year:: 2022
Contributor:: Skvir, Nicholas John (creator); Neretti, Nicola (Advisor); Wu, Zhijin (Reader); Kelsey, Karl (Reader); Istrail, Sorin (Reader); Brown University. Center for Computational Molecular Biology (sponsor)
Genre:: theses
Subject:: epigenetics; DNA--Methylation; Aging
Extent:: xv, 82 p.

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Abstract:: Abstract of An Exploration of the Biology Underlying Epigenetic Clocks by Nicholas J. Skvir, Ph.D., Brown University, October 2022. Epigenetic clocks have gained popularity over the years as an accurate way to predict the age of tissues by measuring the DNA methylation levels at specific CpG dinucleotides that have been determined to be predictive by underlying models. Models such as these are useful in the field of aging biology for their ability to measure changes in predicted ‘biological age’ relative to chronological age, and to observe whether changes are present with anti-aging interventions or with the onset of disease. Despite the widespread use of these models, it was not until very recently that specific explanations were offered to elucidate exactly how they worked and what biological mechanisms were being measured. Here we reconstruct one of the original predictors and expand upon it with over one hundred subsequently-generated clock models across multiple platforms, to create a larger, more comprehensive library of strongly age-predictive CpG sites for pan-tissue and whole-blood-specific datasets. We use this library to show correlation with specific genomic features from a large panel of references. We then compare our libraries of age-predictive CpGs with subsets of CpGs used in cell mixture deconvolution (as well as other significant lists from recent literature), to investigate whether proportional change in cell types with age is truly the primary factor contributing to the predictions made by these models.
Notes:: Thesis (Ph. D.)--Brown University, 2022

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Citation

Skvir, Nicholas John, "An Exploration of the Biology Underlying Epigenetic Clocks" (2022). Center for Computational Molecular Biology Theses and Dissertations. Brown Digital Repository. Brown University Library. https://repository.library.brown.edu/studio/item/bdr:h2d9cxec/

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Center for Computational Molecular Biology Theses and Dissertations

Theses and Dissertations for the Center for Computational Molecular Biology department.
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