자료유형  

 학위논문

Control Number  

0016934506

International Standard Book Number  

9798380484251

Dewey Decimal Classification Number  

330

Main Entry-Personal Name  

Buckley, Matthew T.

Publication, Distribution, etc. (Imprint  

[S.l.] : Stanford University., 2021

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2021

Physical Description  

1 online resource(132 p.)

General Note  

Source: Dissertations Abstracts International, Volume: 85-04, Section: A.

General Note  

Advisor: Engreitz, Jesse;Kundaje, Anshul;Wyss-Coray, Tony;Brunet, Anne.

Dissertation Note  

Thesis (Ph.D.)--Stanford University, 2021.

Restrictions on Access Note  

This item must not be sold to any third party vendors.

Summary, Etc.  

요약Aging is the gradual deterioration of molecular, cellular, and organismal function that occurs over a lifetime. Half of the global adult disease burden is driven by diseases with incidence rates that scale quadratically with age. Understanding and countering the many mechanisms of aging has the potential to reduce or postpone the onset of many diseases simultaneously. However, we are still early in the process of understanding aging and rejuvenating mechanisms, and the tools to achieve this are rapidly improving. In this dissertation I present the work I have undertaken to leverage recent advances in single cell transcriptomics to quantify aging and rejuvenating interventions at the cellular level. I focus on the subventricular zone of the mammalian brain which provides a window into how aging impacts neurogenesis and glial cells critical to brain function. In the second chapter I concentrate on age-associated tissue composition changes; in the third chapter I concentrate on cell type-specific effects. The primary finding I present in the second chapter is the discovery of brain infiltrating CD8+ T cells in the aged neurogenic niche. These T cells are clonally expanded and secrete interferon gamma which negatively impacts the neurogenic potential of the niche. In chapter three, I describe my work building a suite of cell type-specific transcriptomic aging clocks that accurately predict chronological and biological age. I use these clocks to quantify and compare the rejuvenating effects of heterochronic parabiosis and exercise on SVZ cell types. Doing so reveals the particularly striking transcriptomic rejuvenation that young blood exposure imparts on aged neural stem cells. Together, these chapters demonstrate the power of single cell transcriptomics and computational analysis to illuminate processes of aging and their reversal.

Subject Added Entry-Topical Term  

Sparsity.

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DNA methylation.

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Disease.

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Brain research.

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Genomes.

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Epigenetics.

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Ribosomal DNA.

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Genomics.

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Genes.

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Cell cycle.

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T cell receptors.

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Life expectancy.

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Aging.

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Lymphocytes.

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Antigens.

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Stem cells.

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Interferon.

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Cell division.

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Biochemistry.

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Cellular biology.

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Developmental biology.

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Genetics.

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Gerontology.

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Immunology.

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Neurosciences.

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Pharmaceutical sciences.

Added Entry-Corporate Name  

Stanford University.

Host Item Entry  

Dissertations Abstracts International. 85-04A.

Host Item Entry  

Dissertation Abstract International

Electronic Location and Access  

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Control Number  

joongbu:643555