Deactivation of the GATA Transcription Factor ELT-2 Is a Major Driver of Normal Aging in C. elegans

PLoS Genet. 2016 Apr 12;12(4):e1005956. doi: 10.1371/journal.pgen.1005956. eCollection 2016 Apr.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aging / genetics*
  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / genetics*
  • GATA Transcription Factors / genetics*
  • Gene Expression Regulation / genetics
  • Intestines / growth & development
  • Mutation
  • Transcription, Genetic

Substances

  • Caenorhabditis elegans Proteins
  • ELT-2 protein, C elegans
  • GATA Transcription Factors