Date of Award

January 2023

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biomedical Engineering

First Advisor

Sandeep K. Singhal

Abstract

If humans continue to push to be a space exploring species, time and radiation pose the most significant barriers. While not a new idea, approaching a rad-age association with today’s technology offers a fresh look at treating and monitoring both as a similar challenge. To get to that point, starting from square one helps shape the project and avoid common pitfalls. Each chapter is an incremental step to developing this association using multi-omics by building theoretical knowledge of the relationship between radioactive damage and aging processes, building technical knowledge by developing bioinformatic pipelines to integrate different -omes, using genetics data to create a new foundation for associative studies, then integrating epigenetic data to identify potential control mechanisms and corroborate a rad-age assessment. Results of each chapter include (1) a better understanding of how to develop an association and a comprehensive table of biological age indicators, (2) three submodules on processing genetic data, epigenetic data, and integrating the two, (3) using human genetics data to define a 29-year-old threshold between young and old patients to then identify 664 genes from various statistical analyses of age, radiation, sex, and dependent interactions of age and radiation, and (4) integrating human DNA methylation data with previous gene expression findings to narrow the list of genes of interest to 17 statistically significant genes with regard to p-value <0.05 and |fold-change|>2. Functional analysis emphasize pathways dealing with DNA repair, mitochondrial function, immune response, and metabolism with diseases including cardiovascular diseases, cognitive disfunction, and a multitude of cancers. These 17 genes could serve as future starting points for dedicated studies on controlling rad-age outcomes and benefit outlooks on the radiation workforce, cancer radiotherapy, geriatrics, and general aerospace medicine.

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