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020 ▼a 9781085671446
035 ▼a (MiAaPQ)AAI27536481
035 ▼a (MiAaPQ)umichrackham002312
040 ▼a MiAaPQ ▼c MiAaPQ ▼d 247004
0820 ▼a 616
1001 ▼a Mau, Theresa.
24514 ▼a The Effects of Early-Life Drug and Dietary Interventions on Late-Life Disease Development.
260 ▼a [S.l.]: ▼b University of Michigan., ▼c 2019.
260 1 ▼a Ann Arbor: ▼b ProQuest Dissertations & Theses, ▼c 2019.
300 ▼a 130 p.
500 ▼a Source: Dissertations Abstracts International, Volume: 81-02, Section: A.
500 ▼a Advisor: Moore, Bethany B.
5021 ▼a Thesis (Ph.D.)--University of Michigan, 2019.
506 ▼a This item must not be sold to any third party vendors.
506 ▼a This item must not be added to any third party search indexes.
520 ▼a This dissertation is a culmination of several projects that each explore how early-life diet or drug can impact later-life health outcomes. The first chapter is an introduction to provide important context or supplementary information (in addition to the introduction in each chapter).Chapter 2 is a collaborative project testing the adipose-tissue specific effect of three Interventions Testing Program (ITP) drugs that extend median lifespan in mice: acarbose (ACA), 17慣-estradiol (17aE2), and rapamycin (Rapa). We hypothesized these three ITP drugs may extend life through the reduction of adipose tissue inflammation. We found ACA and 17aE2 do not alter adipose tissue inflammation. Rapa-treated HET3 mice have increased M1 adipose tissue macrophages. We conclude that Rapa's lifespan extension benefits occur in the context of exacerbated adipose tissue inflammation.Chapter 3 documents the spontaneous outbreak of C. difficile infection (CDI) in our mouse colony. During this outbreak, methyl-donor supplementation (MS) diet F1 mice had higher mortality than control diet F1 mice. We hypothesized the MS diet alters F1 gut microbiota in a way that increases CDI susceptibility. In Chapter 4, we tested if MS diet affects gut microbiota, and if so, whether these changes affect colonization resistance. We found the MS diet F1 mice gut microbiota is enriched with Lactobacillus, Porphyromonadaceae, and Bacteroides and decreased abundance of certain types of Bacteroides, Akkermansia, and Alistipes. We show that F0 diet can lead to an altered F1 gut microbiota. Interestingly, the altered gut microbiota does not compromise F1 colonization resistance to the 16N203 C. difficile spore dosage we tested.The MS diet is modeled after the diet, epigenetic, and obesity link established in the agouti viable yellow (Avy) mice. In Chapter 5, we hypothesized the MS diet can protect C57BL/6J F1 mice from diet-induced obesity in adult life through reduction of adipose tissue inflammation. We found that the MS diet generally does not alter obesity susceptibility nor metabolic inflammation outcomes in C57BL/6J F1 mice.
590 ▼a School code: 0127.
650 4 ▼a Gerontology.
650 4 ▼a Health sciences.
650 4 ▼a Immunology.
690 ▼a 0982
690 ▼a 0566
690 ▼a 0351
71020 ▼a University of Michigan. ▼b Immunology.
7730 ▼t Dissertations Abstracts International ▼g 81-02A.
773 ▼t Dissertation Abstract International
790 ▼a 0127
791 ▼a Ph.D.
792 ▼a 2019
793 ▼a English
85640 ▼u http://www.riss.kr/pdu/ddodLink.do?id=T15494278 ▼n KERIS ▼z 이 자료의 원문은 한국교육학술정보원에서 제공합니다.
980 ▼a 202002 ▼f 2020
990 ▼a ***1008102
991 ▼a E-BOOK