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Oxidative and energetic stress: regulation of Nrf2 and mitochondrial biogenesis for slowed aging interventions

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dc.contributor.authorBruns, Danielle Reuland, author
dc.contributor.authorHamilton, Karyn L., advisor
dc.contributor.authorMiller, Benjamin F., advisor
dc.contributor.authorWilusz, Carol J., committee member
dc.contributor.authorPagliassotti, Michael J., committee member
dc.date.accessioned2007-01-03T06:08:42Z
dc.date.available2007-01-03T06:08:42Z
dc.date.issued2013
dc.description.abstractThe following dissertation describes a series of experiments with the overall aim to understand the cellular energetic and oxidative stresses associated with aging, and to investigate treatments which may attenuate these stresses and promote healthspan. The specific aims of the four sets of experiments were 1) to determine if treatment with the phytochemicals in Protandim activates Nrf2 and 2) the mechanisms by which this activation occurs; 3) to assess sexually dimorphic Nrf2 signaling across three rodent models of longevity; and 4) to determine if mitochondrial related proteins are preferentially translated under energetic stress. In Experiments #1 and #2, we found that phytochemicals activate Nrf2 and protect cells against oxidant stress. None of the mechanisms we investigated appear to be responsible for phytochemical-induced Nrf2 activation, and continued investigations must be undertaken to identify how Protandim robustly induces Nrf2 nuclear accumulation. In Experiment #3, we found that Nrf2 signaling was not consistently upregulated in tissues from long-lived models compared to controls, but we did elucidate important sex differences, with female mice generally displaying greater Nrf2 signaling than male mice. We believe this finding, in the context of sexual dimorphism in aging, warrants future investigations into Nrf2, stress resistance, and longevity between males and females. In Experiment #4, we found that mitochondrial proteins were preferentially translated upon pharmaceutical energetic stress, and that this selective translation occurred in the vicinity of the mitochondria. Our results indicate activation of Nrf2 protects cells against oxidant stress, and may be a therapeutic target for cardiovascular diseases and other age-related diseases. Further, we assess selective translation of mitochondrial proteins during energetic stress as a means of understanding how energetic stress mimetics selectively facilitate the translation of key mitochondrial proteins. Taken together, these studies provide the basis for future work aimed at attenuating diseases with oxidant stress and mitochondrial dysfunction components.
dc.format.mediumborn digital
dc.format.mediumdoctoral dissertations
dc.identifierBruns_colostate_0053A_12066.pdf
dc.identifierETDF2013500290HAES
dc.identifier.urihttp://hdl.handle.net/10217/80934
dc.languageEnglish
dc.language.isoeng
dc.publisherColorado State University. Libraries
dc.relation.ispartof2000-2019
dc.rightsCopyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see https://libguides.colostate.edu/copyright.
dc.subjectaging
dc.subjectoxidative stress
dc.subjectNrf2
dc.subjectmitochondria
dc.titleOxidative and energetic stress: regulation of Nrf2 and mitochondrial biogenesis for slowed aging interventions
dc.typeText
dcterms.rights.dplaThis Item is protected by copyright and/or related rights (https://rightsstatements.org/vocab/InC/1.0/). You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).
thesis.degree.disciplineHealth and Exercise Science
thesis.degree.grantorColorado State University
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy (Ph.D.)

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