A GATA transcription factor, egl-27, delays aging by promoting stress resistance in C. elegans
- Xiao Xu.
- Aug. 2012.
- Physical description
- online resource (xiii, 118 pages) : illustrations (some color)
- Xu, Xiao.
- Brunet, Anne, 1972- thesis advisor.
- Chua, Katrin Faye. thesis advisor.
- Kim, Stuart thesis advisor (primary).
- Snyder, Michael, Ph. D. thesis advisor.
- Stanford University. Program in Cancer Biology.
- Stanford University. Committee on Graduate Studies. degree grantor.
- Includes bibliographical references (p. 107-118). 122 refs.
- Stress is a fundamental aspect of aging as accumulated damage from a lifetime of stress can limit lifespan, and protective responses to stress can extend lifespan. In this study, we identify a conserved C. elegans GATA transcription factor, egl-27, that is involved in several stress responses and aging. We found that overexpression of egl-27 extends the lifespan of wild-type animals. Furthermore, egl-27 is required for the pro-longevity effects from impaired insulin/IGF-1 like signaling (IIS), as reduced egl-27 activity fully suppresses the longevity of worms that are mutant for the IIS receptor, daf-2. egl-27 expression is inhibited by daf-2 and activated by pro-longevity factors daf-16/FOXO and elt-3/GATA, suggesting that egl-27 acts at the intersection of IIS and GATA pathways to extend lifespan. Consistent with its role in IIS signaling, we found that egl-27 is involved in stress response pathways. egl-27 expression is induced in the presence of multiple stresses, its targets are significantly enriched for many types of stress genes, and altering levels of egl-27 itself affects survival to heat and oxidative stress. Finally, we found that egl-27 expression increases between young and old animals, suggesting that increased levels of egl-27 in aged animals may act to promote stress resistance. These results identify egl-27 as a novel factor that links stress and aging pathways.
- Aging > genetics
- Caenorhabditis elegans > genetics
- Caenorhabditis elegans > metabolism
- Caenorhabditis elegans > physiology
- GATA Transcription Factors
- Stress, Physiological > genetics
- Insulin-Like Growth Factor I
- Oxidative Stress
- Publication date
- Submitted to the Program in Cancer Biology and the Committee on Graduate Studies of Stanford University.
- Thesis (Ph.D.)--Stanford University, 2012.