title: The GATA transcription factor egl-27 delays aging by promoting stress resistance in Caenorhabditis elegans.
abstract: 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 Caenorhabditis 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.
authors.affiliation: Cancer Biology Program and Department of Developmental Biology, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Xiao
authors.initials: X
authors.lastname: Xu
authors.forename: Stuart K
authors.initials: SK
authors.lastname: Kim
mesh_terms: D000375:Aging / Q000235:genetics / Q000502:physiology; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D051858:Forkhead Transcription Factors; D050980:GATA Transcription Factors / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D008136:Longevity / Q000235:genetics / Q000502:physiology; D018384:Oxidative Stress; D013312:Stress, Physiological / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology
chemical_list: D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; C118081:EGL-27 protein, C elegans; D051858:Forkhead Transcription Factors; D050980:GATA Transcription Factors; D007328:Insulin; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; C118721:elt-3 protein, C elegans; D007334:Insulin-Like Growth Factor I