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The Effects of Aging on Circadian Rhythms and the Gut Microbiome.

紀錄類型:	書目-語言資料,手稿 : Monograph/item
正題名/作者:	The Effects of Aging on Circadian Rhythms and the Gut Microbiome./
作者:	Litichevskiy, Lev.
面頁冊數:	1 online resource (119 pages)
附註:	Source: Dissertations Abstracts International, Volume: 85-12, Section: B.
Contained By:	Dissertations Abstracts International85-12B.
標題:	Microbiology. -
電子資源:	click for full text (PQDT)
ISBN:	9798382830346

The Effects of Aging on Circadian Rhythms and the Gut Microbiome.
Litichevskiy, Lev.

The Effects of Aging on Circadian Rhythms and the Gut Microbiome. - 1 online resource (119 pages)

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

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

Includes bibliographical references

Advanced 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.

Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2024

Mode of access: World Wide Web

ISBN: 9798382830346Subjects--Topical Terms:

591510
Microbiology.
Subjects--Index Terms:

Dietary restrictionIndex Terms--Genre/Form:

554714
Electronic books.

The Effects of Aging on Circadian Rhythms and the Gut Microbiome.
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520 $a Advanced 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.
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