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|Title:||Developing a Model for Stress-Associated Telomere Shortening: Effects of Stress-Related Mediators on Telomerase Activity|
|Abstract:||Telomere length is inversely correlated with aging, risk of chronic diseases, and exposure to chronic stress. Chronic stress is also associated with detrimental outcomes including cardiovascular disease and cancer. Prior work indicates that exposure to the stress hormone, cortisol, decreases the activity of telomerase (a ribonucleoprotein complex) in human foreskin fibroblasts (HFF) and T-lymphocytes. However, little is known about the mechanism by which cortisol and other stress hormones might affect telomerase activity and telomere length. To evaluate the mechanism underlying stress-associated telomere attrition, we employed a model in which HFF were exposed to stress-related mediators. We investigated the effects of 48 hours of hydrocortisone treatment on telomerase activity, telomere length, and RNA expression of several telomere-associated genes in HFF cells. Since telomerase is expressed during the S-phase, flow cytometry was used to determine the number of cells in the S-phase to correct for telomerase activity. To broaden our understanding of the physiological effects of stress, we also examined the effects of TNF-alpha, a key mediator of inflammation, on HFF telomerase activity and cell cycle. HFF telomerase activity decreased significantly in response to hydrocortisone treatment, whereas telomere length did not differ. RNA expression of TRF2, TPP1, POT1, and TNKS in HFF were significantly down-regulated after hydrocortisone treatment. A suggestive decrease was seen in TERC expression. The addition of TNF-alpha did not significantly alter HFF telomerase activity. Variability among results call for further experimentation and optimization. Nevertheless, these findings offers a starting point to uncovering the mechanistic dynamics of telomerase activity, which can reinforce our understanding of stress-associated telomere shortening.|
|Type of Material:||Princeton University Senior Theses|
|Appears in Collections:||Molecular Biology, 1954-2020|
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