Quantification of aging and rejuvenation interventions on the neurogenic niche using single cell transcriptomics
Abstract/Contents
- Abstract
- Aging 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.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2021; ©2021 |
| Publication date | 2021; 2021 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Buckley, Matthew |
|---|---|
| Degree supervisor | Brunet, Anne, 1972- |
| Thesis advisor | Brunet, Anne, 1972- |
| Thesis advisor | Engreitz, Jesse |
| Thesis advisor | Kundaje, Anshul, 1980- |
| Thesis advisor | Wyss-Coray, Anton |
| Degree committee member | Engreitz, Jesse |
| Degree committee member | Kundaje, Anshul, 1980- |
| Degree committee member | Wyss-Coray, Anton |
| Associated with | Stanford University, Department of Genetics |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Matthew T. Buckley. |
|---|---|
| Note | Submitted to the Department of Genetics. |
| Thesis | Thesis Ph.D. Stanford University 2021. |
| Location | https://purl.stanford.edu/vr097zp4337 |
Access conditions
- Copyright
- © 2021 by Matthew Buckley
- License
- This work is licensed under a Creative Commons Attribution 3.0 Unported license (CC BY).
Also listed in
Loading usage metrics...