2026-09-21T07:36:31Zhttps://api.mountainscholar.org/server/oai/request

oai:mountainscholar.org:10217/2384662026-06-11T19:59:39Zcom_10217_100532com_10217_100000com_10217_100447com_10217_100303col_10217_182111col_10217_100449

Walsh, Maureen Ann, author Hamilton, Karyn L., advisor Fling, Brett W., committee member Moreno, Julie A., committee member LaRocca, Thomas J., committee member Santangelo, Kelly S., committee member 2024-05-27T10:32:46Z 2026-05-20 2024 Walsh_colostate_0053A_18205.pdf https://hdl.handle.net/10217/238466 https://doi.org/10.25675/3.02614 There is a growing population of older adults (>65+ years) worldwide that is projected to increase in coming decades, presenting both a challenge and an opportunity. Specifically, age is the number one risk factor for chronic diseases like sarcopenia, the loss of muscle mass and function, and neurodegenerative diseases such as Alzheimer's Disease. The twelve hallmarks of aging are a collection of cellular changes that drive the aging process. Two highly interconnected hallmarks of aging that drive the development and progression of sarcopenia and neurodegeneration are loss of proteostasis (protein homeostasis) and mitochondrial dysfunction. While progress has been made in understanding the etiology of chronic diseases, treatments for age-related chronic diseases affecting skeletal muscle and the brain are lacking. One reason for the lack of effective treatments in humans is the absence of preclinical animal models that recapitulate human aging. However, our group previously identified the Hartley guinea pig as a novel model of brain and skeletal muscle aging. We then treated these guinea pigs with a phytochemical compound to delay the onset and/or slow the progression of brain and skeletal muscle aging. Through the experiments in this dissertation, I observed that: 1.) phytochemical compounds, branded as Protandim, can improve mechanisms of proteostasis independent of changes in mitochondrial respiration in muscle precursor cells; 2.) the phytochemical compound, branded as PB125, can improve mechanisms of skeletal muscle proteostasis in the Hartley guinea pig; 3.) PB125 can also decrease neuroinflammation in the Hartley guinea pig; and 4.) despite the lack of declines in hippocampal mitochondrial respiration with age, Hartley guinea pigs exhibit decreased mitochondrial efficiency. Collectively, this dissertation builds on prior work suggesting that the Hartley guinea pig is a valuable model to test preclinical interventions. born digital doctoral dissertations English eng Colorado State University. Libraries 2020- Copyright 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. Targeting proteostatic maintenance and mitochondrial function with phytochemical compounds in models of brain and skeletal muscle aging Text 2026-05-20 2026-05-20 This 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). Doctor of Philosophy (Ph.D.) Doctoral Health and Exercise Science Colorado State University open.access