Investigating the relationship between DNA damage and hormesis in saccharomyces cerevisiae chronological aging

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Authors
Ross, Emily Morgan
Issue Date
2017-08
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Electronic thesis
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ENG
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Biology
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Abstract
In addition, a preliminary analysis of expression levels of DNA damage response genes found that they were upregulated during normal aging, but exposure to an exogenous stress did not further activate these genes in aged cells, providing evidence for a decline in DNA damage response with age in S. cerevisiae. We found that low doses of several DNA damaging agents induce a hormetic lifespan extension in S. cerevisiae when administered to cells during growth. Hormesis is a widespread phenomenon in which organisms that are exposed to low doses of stressors exhibit a beneficial cellular response. There are many possible mechanisms behind hormesis, including upregulated stress responses, mitochondrial activity leading to elevated ROS, and increased levels of autophagy. The increase in chronological lifespan induced by DNA damaging agents was not associated with increased stress resistance, but was associated with improved entry into quiescence, a temporary arrest of the cell cycle that is important for healthy aging. Knocking out genes that are involved in promoting quiescence prevented lifespan extension, providing further evidence that the hormetic lifespan extension after exposure to low doses of DNA damaging agents during growth is linked to quiescence. Further studying these factors may be relevant to promoting healthy aging in humans.
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August 2017
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Rensselaer Polytechnic Institute, Troy, NY
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