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Folate Metabolism in Yeast Cell Cycle and Mouse Healthspan
Abstract
Folate, or vitamin B9, is a key component in one-carbon (1C) metabolism that supports precursor molecules required for growth and development. Folate is found in some natural foods, and its synthetic form is called folic acid (FA). Insufficient folate levels in pregnant women cause fetal neural tube defects (NTDs) and other birth defects. To increase folate intake, FDA mandated in 1998 that FA be included in fortified processed food. My dissertation work queries aspects of 1C enzyme roles in cell cycle progression and dietary folate’s impact on healthspan in aging mice. In my first dissertation project, I used budding yeast S. cerevisiae as a cell cycle model. I measured levels of three 1C enzymes during the cell cycle to confirm previous predictions of their translational control. Next, I used individual knockout strains to determine individual 1C enzyme effects on cell size, cell cycle progression, and metabolome profiles. These results contribute to the understanding of processes in cell growth and division. In my second dissertation project, I introduced a completely folate- and choline-deficient (FC-) diet in aged mice of a long-lived wildtype strain. Standardized phenotyping protocols were used to evaluate healthspan before the diet switch and periodically after until death. I show that healthspan phenotypes either improved or did not change on the FC- diet. This study serves as a preliminary test to re-evaluate FA fortification in an aging general population. Overall, my dissertation work unveils folate cycle impacts at both cellular and physiological levels that invite more questions to answer.
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Citation
Hammer, Staci Elizabeth (2023). Folate Metabolism in Yeast Cell Cycle and Mouse Healthspan. Doctoral dissertation, Texas A&M University. Available electronically from https : / /hdl .handle .net /1969 .1 /203059.