자료유형  

 학위논문

Control Number  

0017161331

International Standard Book Number  

9798382830346

Dewey Decimal Classification Number  

576

Main Entry-Personal Name  

Litichevskiy, Lev.

Publication, Distribution, etc. (Imprint  

[S.l.] : University of Pennsylvania., 2024

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2024

Physical Description  

119 p.

General Note  

Source: Dissertations Abstracts International, Volume: 85-12, Section: B.

General Note  

Advisor: Thaiss, Christoph A.;Li, Mingyao;Bushman, Frederic D.

Dissertation Note  

Thesis (Ph.D.)--University of Pennsylvania, 2024.

Summary, Etc.  

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.

Subject Added Entry-Topical Term  

Microbiology.

Subject Added Entry-Topical Term  

Aging.

Subject Added Entry-Topical Term  

Health sciences.

Subject Added Entry-Topical Term  

Immunology.

Subject Added Entry-Topical Term  

Nutrition.

Index Term-Uncontrolled  

Dietary restriction

Index Term-Uncontrolled  

Diversity Outbred mice

Index Term-Uncontrolled  

Gut microbiome

Index Term-Uncontrolled  

Circadian rhythms

Added Entry-Corporate Name  

University of Pennsylvania Genomics and Computational Biology

Host Item Entry  

Dissertations Abstracts International. 85-12B.

Electronic Location and Access  

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Control Number  

joongbu:658667