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Novel insights into protein synthesis rates in the brain following two lifespan-extending treatments

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dc.contributor.authorReid, Justin, author
dc.contributor.authorHamilton, Karyn, advisor
dc.contributor.authorMiller, Benjamin, advisor
dc.contributor.authorTsunoda, Susan, committee member
dc.date.accessioned2018-09-10T20:04:31Z
dc.date.available2018-09-10T20:04:31Z
dc.date.issued2018
dc.description.abstractThe number of individuals 65 years or older is rapidly increasing. Aging is the predominant risk factor for chronic disease and disability. Dramatic increases in the number of individuals living with chronic disease or disability will present unique societal challenges. Accordingly, much research has focused on treatments that slow the aging process to prevent many chronic diseases simultaneously. Treatments using two pharmaceuticals, rapamycin and rapamycin plus metformin, have been shown to extend lifespan and improve health in model organisms. Neurodegenerative diseases represent an important subset of debilitating chronic diseases, for which treatment is currently limited. The use of slowed aging treatments in research of neurological function may provide insight into causes of neurodegenerative disease. Protein homeostasis (proteostasis) is crucial for cell and organismal health. Loss of proteostasis is characteristic of aging and chronic disease, and slowed aging treatments improve proteostasis-related outcomes. Protein synthesis is a necessary component of proteostasis. The effect of rapamycin and rapamycin plus metformin on protein synthesis rates in vivo is unexplored. Investigation into the effect of both slowed aging treatments on protein synthesis rates in the brain could inform effects on neuronal health, which may have implications for neurodegeneration. The purpose of the current study is to establish the use of deuterium oxide as a stable isotopic tracer for brain protein synthesis rates in vivo, and to determine the effect of two slowed aging treatments on brain protein synthesis rates. Supportive measurements related to proteostasis were also made. Deuterium oxide labeling allowed for measurement of subcellular brain protein synthesis rates with ample sensitivity to detect sex differences and responses to treatment. The results demonstrated a strong influence of sex in response to both rapamycin and rapamycin plus metformin. Both slowed aging treatments had differing effects on protein synthesis as well as other markers of proteostasis. This study is the first to demonstrate the use of deuterium oxide for protein synthesis rates in the brain, which represents a novel methodology for evaluating proteostasis in neuronal tissue. Further, this is the first study to explore and reveal the effects of rapamycin and rapamycin with metformin on protein synthesis rates in the brain. Future studies using these methods and slowed aging interventions in models of neurodegenerative disease may prove insightful in determining causes, pathologies, and treatments of age-related neurological disorders.
dc.format.mediumborn digital
dc.format.mediummasters theses
dc.identifierReid_colostate_0053N_14910.pdf
dc.identifier.urihttps://hdl.handle.net/10217/191325
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.titleNovel insights into protein synthesis rates in the brain following two lifespan-extending treatments
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.levelMasters
thesis.degree.nameMaster of Science (M.S.)

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