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The Effects of Aging on Circadian Rhythms and the Gut Microbiome
The Effects of Aging on Circadian Rhythms and the Gut Microbiome
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20250211151341
- ISBN
- 9798382830346
- DDC
- 576
- 서명/저자
- The Effects of Aging on Circadian Rhythms and the Gut Microbiome
- 발행사항
- [Sl] : University of Pennsylvania, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 119 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 85-12, Section: B.
- 주기사항
- Advisor: Thaiss, Christoph A.;Li, Mingyao;Bushman, Frederic D.
- 학위논문주기
- Thesis (Ph.D.)--University of Pennsylvania, 2024.
- 초록/해제
- 요약Advanced age is the greatest risk factor for the most devastating diseases of our time, including cancer, neurodegeneration, and cardiovascular disease. A better understanding of aging may help us to understand and treat these diseases. Here, I examine in mice how aging affects two aspects of health: circadian rhythms and the gut microbiome. First, I show that aging impairs the diurnal rhythmicity of immune function and gene expression in macrophages. Chromatin accessibility, unlike gene expression, shows no diurnal rhythmicity, suggesting that changes in chromatin accessibility do not drive rhythmic cellular function. Second, I examine a large cohort of genetically diverse mice to assess how aging influences the gut microbiome. This cohort consists of 960 mice assigned to various lifespan-extending dietary interventions. The health of these mice was assessed longitudinally with numerous readouts, and stool samples were collected for characterization of the gut microbiome. I performed metagenomic sequencing of 2997 stool samples to generate the largest-to-date mouse gut microbiome dataset. I find that the microbiome changes with age but that these changes appear to result from stochastic community development, rather than the influence of an aging host. Lastly, I leverage this dataset to describe how dietary restriction and host genetics influence the gut microbiome and, in turn, how the microbiome influences health. I find that the microbiome is associated with several host phenotypes, including body weight and composition, but not with lifespan. In summary, my work advances our understanding of how aging influences two key aspects of health (circadian rhythms and the gut microbiome); cautions against attempting to extend lifespan via gut microbiome interventions; and produced a valuable dataset for the microbiome community.
- 일반주제명
- Microbiology
- 일반주제명
- Aging
- 일반주제명
- Health sciences
- 일반주제명
- Immunology
- 일반주제명
- Nutrition
- 키워드
- Gut microbiome
- 기타저자
- University of Pennsylvania Genomics and Computational Biology
- 기본자료저록
- Dissertations Abstracts International. 85-12B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■00520250211151341
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■020 ▼a9798382830346
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■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a576
■1001 ▼aLitichevskiy, Lev.
■24510▼aThe Effects of Aging on Circadian Rhythms and the Gut Microbiome
■260 ▼a[Sl]▼bUniversity of Pennsylvania▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a119 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 85-12, Section: B.
■500 ▼aAdvisor: Thaiss, Christoph A.;Li, Mingyao;Bushman, Frederic D.
■5021 ▼aThesis (Ph.D.)--University of Pennsylvania, 2024.
■520 ▼aAdvanced age is the greatest risk factor for the most devastating diseases of our time, including cancer, neurodegeneration, and cardiovascular disease. A better understanding of aging may help us to understand and treat these diseases. Here, I examine in mice how aging affects two aspects of health: circadian rhythms and the gut microbiome. First, I show that aging impairs the diurnal rhythmicity of immune function and gene expression in macrophages. Chromatin accessibility, unlike gene expression, shows no diurnal rhythmicity, suggesting that changes in chromatin accessibility do not drive rhythmic cellular function. Second, I examine a large cohort of genetically diverse mice to assess how aging influences the gut microbiome. This cohort consists of 960 mice assigned to various lifespan-extending dietary interventions. The health of these mice was assessed longitudinally with numerous readouts, and stool samples were collected for characterization of the gut microbiome. I performed metagenomic sequencing of 2997 stool samples to generate the largest-to-date mouse gut microbiome dataset. I find that the microbiome changes with age but that these changes appear to result from stochastic community development, rather than the influence of an aging host. Lastly, I leverage this dataset to describe how dietary restriction and host genetics influence the gut microbiome and, in turn, how the microbiome influences health. I find that the microbiome is associated with several host phenotypes, including body weight and composition, but not with lifespan. In summary, my work advances our understanding of how aging influences two key aspects of health (circadian rhythms and the gut microbiome); cautions against attempting to extend lifespan via gut microbiome interventions; and produced a valuable dataset for the microbiome community.
■590 ▼aSchool code: 0175.
■650 4▼aMicrobiology
■650 4▼aAging
■650 4▼aHealth sciences
■650 4▼aImmunology
■650 4▼aNutrition
■653 ▼aDietary restriction
■653 ▼aDiversity Outbred mice
■653 ▼aGut microbiome
■653 ▼aCircadian rhythms
■690 ▼a0410
■690 ▼a0493
■690 ▼a0566
■690 ▼a0982
■690 ▼a0570
■71020▼aUniversity of Pennsylvania▼bGenomics and Computational Biology.
■7730 ▼tDissertations Abstracts International▼g85-12B.
■790 ▼a0175
■791 ▼aPh.D.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17161331▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
