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Targeting skeletal muscle mitochondrial function with a Nrf2 activator in a novel model of musculoskeletal decline

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dc.contributor.authorMusci, Robert Vincent, author
dc.contributor.authorHamilton, Karyn L., advisor
dc.contributor.authorHickey, Matthew S., committee member
dc.contributor.authorLark, Daniel S., committee member
dc.contributor.authorSantangelo, Kelly S., committee member
dc.date.accessioned2020-06-22T11:53:47Z
dc.date.available2021-06-15T11:53:47Z
dc.date.issued2020
dc.description.abstractThis dissertation describes a series of three experiments with an overall objective to understand how targeting mitochondrial function with a phytochemical Nrf2 activator can prevent the onset of or mitigate the progression of mitochondrial dysfunction and sarcopenia in a novel model of musculoskeletal aging. The specific aims of the three experiments were to 1) characterize the age-related changes in skeletal muscle in Dunkin-Hartley guinea pigs; 2) assess the effect of Nrf2 activator treatment on skeletal muscle energetics by measuring mitochondrial function; and 3) determine how Nrf2 activator treatment influences components of skeletal muscle proteostasis. Dunkin-Hartley guinea pigs exhibit several characteristics reflective of human musculoskeletal aging including a decline in the proportion of type II muscle fibers, a shift towards a smaller myofiber size distribution, and a decline in muscle density in the gastrocnemius, as well as a decline in protein synthesis in both the soleus and gastrocnemius. In the second experiment, Nrf2 activator treatment improved mitochondrial respiration in both 5- and 15-month-old male and female guinea pigs. Moreover, Nrf2 activator treatment attenuated the age-related decline in mitochondrial respiration. In the third experiment, Nrf2 activator treatment attenuated the age-related decline in protein synthesis in Dunkin-Hartley guinea pigs. Altogether, these data demonstrate 1) Dunkin-Hartley guinea pigs experience age-related changes in skeletal muscle consistent with the aged musculoskeletal phenotype in humans 2) this phytochemical Nrf2 activator can improve mitochondrial function and 3) targeting mitochondrial dysfunction is an efficacious intervention to mitigate age-related declines in components of proteostasis in skeletal muscle and improve overall musculoskeletal function.
dc.format.mediumborn digital
dc.format.mediumdoctoral dissertations
dc.identifierMusci_colostate_0053A_15966.pdf
dc.identifier.urihttps://hdl.handle.net/10217/208559
dc.languageEnglish
dc.language.isoeng
dc.publisherColorado State University. Libraries
dc.relation.ispartof2020-
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.subjectenergetics
dc.subjectproteostasis
dc.subjectaging
dc.subjectskeletal muscle
dc.subjectmitochondria
dc.titleTargeting skeletal muscle mitochondrial function with a Nrf2 activator in a novel model of musculoskeletal decline
dc.typeText
dcterms.embargo.expires2021-06-15
dcterms.embargo.terms2021-06-15
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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