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Is exercise-induced redox signaling affected by aging?

Ostrom, Ethan Lambert (2021) Is exercise-induced redox signaling affected by aging? Doctoral thesis, Northern Arizona University.

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Redox signaling dysfunction is a key characteristic of aging cells and tissues and has wide ranging cellular and physiological effects. Exercise is one of the best tools available to promote healthy aging and reduce disease burden, however some evidence suggests exercise is not as effective in older populations. This is likely driven by redox signaling dysfunction because of the critical involvement of redox signaling mechanisms in exercise adaptations. In this work, I have used several studies in humans and mice with multiple methods to elucidate the mechanisms of Nrf2-mediated redox stress response to exercise and the effects of aging on this response. I demonstrate that exercise induced Nrf2 activation is impaired in older compared to younger adults, and that exercise training only partially reverses these effects. Redox stress responses to a non-exercise stressor, a forearm ischemia-reperfusion challenge, is not different between ages, but exercise training does improve the response compared to controls in humans. Finally, acute contractile stimulation of skeletal muscle increases Nrf2 signaling within the muscle, and high intensity stimulation activates Nrf2 in contralateral unstimulated muscle, but low intensity stimulation does not. These effects appear to occur through inhibiting the negative regulator, Keap1. Taken together, these data indicate that exercise is a powerful inducer of the redox stress response transcription factor, Nrf2, but that aging impairs our ability to respond to an acute exercise bout. Future work should aim to discover and utilize therapeutics that act synergistically with exercise to restore redox homeostasis and redox signaling function.

Item Type: Thesis (Doctoral)
Publisher’s Statement: © Copyright is held by the author. Digital access to this material is made possible by the Cline Library, Northern Arizona University. Further transmission, reproduction or presentation of protected items is prohibited except with permission of the author.
Keywords: Aging; Exercise; Redox Biology
Subjects: Q Science > QP Physiology
MeSH Subjects: A Anatomy > A02 Musculoskeletal System
NAU Depositing Author Academic Status: Student
Department/Unit: Graduate College > Theses and Dissertations
College of the Environment, Forestry, and Natural Sciences > Biological Sciences
Date Deposited: 05 Jul 2022 22:12
Last Modified: 06 Jul 2022 08:30
URI: https://openknowledge.nau.edu/id/eprint/5804

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