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Vitamin D, Klotho, and FOXO3 have all been linked to have anti-aging and anti-cancerous effects as separate pathways. Specifically, mice with knockout Klotho in their genes have displayed signs of premature aging, humans who are vitamin D deficient have been shown to develop cardiovascular disease and cognitive impairments, and those who have displayed overexpression of FOXO3 have shown to have a longer lifespan. Here we took each pathway and attempted to formulate a feedback mechanism loop linking all three separate pathways. We propose that vitamin D levels modulate klotho activity, including the expression of the s-klotho and m-klotho isoforms. Moreover, the anti-oxidation transcription factor FOXO3 is also thought to participate in crosstalk with VDR signaling. Through the connection between 1,25D and Klotho, we probed at their interactions with FOXO3 signaling in kidney and colon cells, and proposed that vitamin D and klotho may reduce oxidative stress and suppress the onset of epithelial cancers through it effects on FOXO3. Results showed a strong support for the cooperation between FOXO3 and 1,25D to stimulate both superoxide dismutase (a FOXO3 response element) and XDR3/ROC (vitamin D response elements). This cooperation was mostly seen in embryonic kidney cells (HEK293) and not in the colon cancer cells (HCT116), which has led to the conclusion that vitamin D and FOXO3 cooperation mainly occurs in kidney tissue and/or in tissue that is not yet been overtaken by cancer. Differences in the Klotho isoforms were seen when measuring FOXO3 and vitamin D activity, but experiments manipulating other components will need to be conducted to further understand the function of Klotho in maintaining reactive oxygenated species levels.
ContributorsSandoval, Ruby (Author) / Jurutka, Peter (Thesis director) / Sandrin, Todd R. (Committee member) / Heck, Michael (Committee member) / School of Social and Behavioral Sciences (Contributor) / School of Mathematical and Natural Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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Increasing prices of pharmaceutical grade prescription drugs have caused hospitals, insurance companies, and patients to search for alternative methods of treating illness. The pharmaceutical industry must find ways of lowering the costs associated with prescription drugs to avoid further scrutiny, increased regulation, and staggering profits. The use of RFID technology will increase transparency of information flow within the supply chain and reduce costs associated with recalls, counterfeits, and expired products. The failure to reduce costs in pharmaceuticals and decreased profits have introduced natural supplements into the market. Without the need for FDA regulation and clinical trials, the pharmaceutical industry has developed supplements with the potential benefits of increasing lifespan. The organic molecule, resveratrol, and its ability to mimic the effects of caloric restriction increasing lifespan in smaller organisms has translated to its use in humans. With the future of increased lifespan and youthful aging, the study of sirtuin activating compounds (STACS) and telomere lengthening will become the future of anti-aging cosmetics.
ContributorsOrtega, Victor (Author) / Printezis, Antonios (Thesis director) / Garg, Vikas (Committee member) / Barrett, The Honors College (Contributor)
Created2015-12