Identifying a new driver of aging in C. elegans

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Aging is a fundamental biological process seen in nearly all organisms. While research has discovered hundreds of genes whose dosage can modify lifespan, it is unclear how many of these genes play a role in the normal transition from the young state to the old state. To better understand aging, it is critical to identify which processes are driving aging in wildtype organisms. Our approach is to search for direct regulators of molecular changes that appear over time in the nematode worm Caenorhabditis elegans. This is a quantitative, global, and relatively unbiased way to find potential drivers of aging. We begin with a set of over 1,000 gene expression changes between young and old worms. In this work, we used a computational screen to identify transcription factors that directly bind to our list of age-regulated genes. The top hit from our screen is a conserved GATA transcription factor called ELT-2 that functions during development to effect the terminal differentiation of the intestine. The expression of ELT-2 and its direct transcriptional targets decline during aging. Lifespan can be either extended or shortened by increasing or decreasing the dosage of ELT-2. Together, these findings provide strong evidence to support the idea that changes in the expression of ELT-2 drive transcriptional changes during aging and limit lifespan.


Type of resource text
Form electronic; electronic resource; remote
Extent 1 online resource.
Publication date 2016
Issuance monographic
Language English


Associated with Mann, Frederick George, Jr
Associated with Stanford University, Department of Genetics.
Primary advisor Kim, Stuart
Thesis advisor Kim, Stuart
Thesis advisor Brunet, Anne, 1972-
Thesis advisor Fire, Andrew Zachary
Thesis advisor Villeneuve, Anne, 1959-
Advisor Brunet, Anne, 1972-
Advisor Fire, Andrew Zachary
Advisor Villeneuve, Anne, 1959-


Genre Theses

Bibliographic information

Statement of responsibility Frederick George Mann, Jr.
Note Submitted to the Department of Genetics.
Thesis Thesis (Ph.D.)--Stanford University, 2016.
Location electronic resource

Access conditions

© 2016 by Frederick George Mann
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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