Partial reprogramming of the aging neurogenic niche as a potential rejuvenation strategy
Abstract/Contents
- Abstract
- Aging is associated with a decline in function of cells and tissues, accompanied by a dramatic increase in the incidence of many diseases including neurodegenerative diseases and cancers. Importantly, the accumulation of age-associated changes is not inevitable. Understanding how to slow down or potentially even reverse the process of aging in different cell types is critical to the goal of preserving tissue function and organism health during aging. One interesting strategy to reverse aging is reprogramming, through the forced expression of the Yamanaka reprogramming factors OCT4, SOX2, KLF4, and c-MYC (OSKM). Reprogramming of somatic cells by constant expression of OSKM results in embryonic stem cell-like cells and erases many hallmarks of aging in vitro. However, the impact of OSKM expression on cell function and heterogeneity in specific cell types in old animals is not fully known. In this dissertation, I present my work on aging and reprogramming. First, I discuss several categories of rejuvenation strategies that have recently been studied in mice, including soluble blood factors, manipulation of diet and metabolism, killing of senescent cells, and reprogramming. Next, I explore how partial reprogramming affects the subventricular zone (SVZ), a conserved neurogenic niche in mammalian brains. Partial reprogramming, achieved by expression OSKM in a time- or cell-restricted manner, has been shown to improve function in a variety of cell types from aging mice without permanent loss of cell identity. But the impact of partial reprogramming on the aging brain is largely unknown. I focus on the SVZ, a neurogenic niche which holds intrinsic regenerative potential, as neural stem cells from the SVZ can give rise to newborn neurons and astrocytes throughout adulthood. Lastly, I examine the impact of aging and heterogeneity on reprogramming of fibroblasts, the most commonly used cell type for reprogramming to pluripotency. Together, these studies demonstrate the complex interplay between aging and reprogramming, and the potential for reprogramming to be applied as a tool to counteract age-related decline.
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 | 2022; ©2022 |
| Publication date | 2022; 2022 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Xu, Lucy |
|---|---|
| Degree supervisor | Brunet, Anne, 1972- |
| Thesis advisor | Brunet, Anne, 1972- |
| Thesis advisor | Dixon, Scott James, 1977- |
| Thesis advisor | Nakauchi, Hiromitsu, 1952- |
| Thesis advisor | Shen, Kang, 1972- |
| Thesis advisor | Wyss-Coray, Anton |
| Degree committee member | Dixon, Scott James, 1977- |
| Degree committee member | Nakauchi, Hiromitsu, 1952- |
| Degree committee member | Shen, Kang, 1972- |
| Degree committee member | Wyss-Coray, Anton |
| Associated with | Stanford University, Department of Biology |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Lucy Xu. |
|---|---|
| Note | Submitted to the Department of Biology. |
| Thesis | Thesis Ph.D. Stanford University 2022. |
| Location | https://purl.stanford.edu/ck834ff5386 |
Access conditions
- Copyright
- © 2022 by Lucy Xu
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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