Persistent Link:
http://hdl.handle.net/10150/321459
Title:
Lifespan Extension, Nutrient Sensing and Immune Competence
Author:
Goldberg, Emily L.
Issue Date:
2014
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
Immune protection wanes during aging. This is evidenced by increased morbidity and mortality from infectious disease in aged individuals. As the aging population continues to increase worldwide, it will become increasingly important to determine both causes and therapeutic strategies for defects in the aged immune response. In particular, CD8 T cells have been shown to be highly susceptible to age-related defects. Recently, metabolic pathways have been implicated as critical factors in T cell fate decisions during immune responses. Of note, metabolic pathways are also considered primary determinants of lifespan in mammals. Therefore, we hypothesized that metabolic manipulations to extend lifespan would have significant effects on the aging immune system and protection during infection. In particular, we investigated the impact of rapamycin (rapa), both acute and chronic treatment regimens, on adult and old mice. Specifically, we tested how T cell development, peripheral homeostasis, and effector immunity became altered during treatment. We made side-by-side comparisons in calorically restricted (CR) old mice as a gold standard model of longevity extension. Importantly, both of these interventions have been reported to benefit immune function and extend lifespan in mice. However, our data strongly indicate that both rapa and CR induce distinct but deleterious consequences to overall immunity in mice. We conclude that neither rapa nor CR may be ideal candidates for extending lifespan in humans.
Type:
text; Electronic Dissertation
Keywords:
CD8 T cell; Healthspan; metabolism; nutrient sensing; Nutritional Sciences; Aging
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Nutritional Sciences
Degree Grantor:
University of Arizona
Advisor:
Nikolich-Zugich, Janko

Full metadata record

DC FieldValue Language
dc.language.isoen_USen
dc.titleLifespan Extension, Nutrient Sensing and Immune Competenceen_US
dc.creatorGoldberg, Emily L.en_US
dc.contributor.authorGoldberg, Emily L.en_US
dc.date.issued2014-
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractImmune protection wanes during aging. This is evidenced by increased morbidity and mortality from infectious disease in aged individuals. As the aging population continues to increase worldwide, it will become increasingly important to determine both causes and therapeutic strategies for defects in the aged immune response. In particular, CD8 T cells have been shown to be highly susceptible to age-related defects. Recently, metabolic pathways have been implicated as critical factors in T cell fate decisions during immune responses. Of note, metabolic pathways are also considered primary determinants of lifespan in mammals. Therefore, we hypothesized that metabolic manipulations to extend lifespan would have significant effects on the aging immune system and protection during infection. In particular, we investigated the impact of rapamycin (rapa), both acute and chronic treatment regimens, on adult and old mice. Specifically, we tested how T cell development, peripheral homeostasis, and effector immunity became altered during treatment. We made side-by-side comparisons in calorically restricted (CR) old mice as a gold standard model of longevity extension. Importantly, both of these interventions have been reported to benefit immune function and extend lifespan in mice. However, our data strongly indicate that both rapa and CR induce distinct but deleterious consequences to overall immunity in mice. We conclude that neither rapa nor CR may be ideal candidates for extending lifespan in humans.en_US
dc.typetexten
dc.typeElectronic Dissertationen
dc.subjectCD8 T cellen_US
dc.subjectHealthspanen_US
dc.subjectmetabolismen_US
dc.subjectnutrient sensingen_US
dc.subjectNutritional Sciencesen_US
dc.subjectAgingen_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplineNutritional Sciencesen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorNikolich-Zugich, Jankoen_US
dc.contributor.committeememberNikolich-Zugich, Jankoen_US
dc.contributor.committeememberLimesand, Kirstenen_US
dc.contributor.committeememberThomson, Cynthiaen_US
dc.contributor.committeememberFrelinger, Jeffreyen_US
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