title: Deactivation of the GATA Transcription Factor ELT-2 Is a Major Driver of Normal Aging in C. elegans.
abstract: To understand the molecular processes underlying aging, we screened modENCODE ChIP-seq data to identify transcription factors that bind to age-regulated genes in C. elegans. The most significant hit was the GATA transcription factor encoded by elt-2, which is responsible for inducing expression of intestinal genes during embryogenesis. Expression of ELT-2 decreases during aging, beginning in middle age. We identified genes regulated by ELT-2 in the intestine during embryogenesis, and then showed that these developmental genes markedly decrease in expression as worms grow old. Overexpression of elt-2 extends lifespan and slows the rate of gene expression changes that occur during normal aging. Thus, our results identify the developmental regulator ELT-2 as a major driver of normal aging in C. elegans.
authors.affiliation: Departments of Genetics and Developmental Biology, Stanford University Medical Center, Stanford, California, United States of America.
authors.forename: Frederick G
authors.initials: FG
authors.lastname: Mann
authors.affiliation: Department of Cellular and Molecular Medicine, Institute of Genomic Medicine, University of California, San Diego, La Jolla, California, United States of America.
authors.forename: Eric L
authors.initials: EL
authors.lastname: Van Nostrand
authors.affiliation: Editas Medicine, Cambridge, Massachusetts, United States of America.
authors.forename: Ari E
authors.initials: AE
authors.lastname: Friedland
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Liu
authors.affiliation: Departments of Genetics and Developmental Biology, Stanford University Medical Center, Stanford, California, United States of America.
authors.forename: Stuart K
authors.initials: SK
authors.lastname: Kim
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D050980:GATA Transcription Factors / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics; D007422:Intestines / Q000254:growth & development; D009154:Mutation; D014158:Transcription, Genetic
chemical_list: D029742:Caenorhabditis elegans Proteins; C094134:ELT-2 protein, C elegans; D050980:GATA Transcription Factors