An elt-3/elt-5/elt-6 GATA transcription circuit guides aging in C. elegans

Cell. 2008 Jul 25;134(2):291-303. doi: 10.1016/j.cell.2008.05.044.

Abstract

To define the C. elegans aging process at the molecular level, we used DNA microarray experiments to identify a set of 1294 age-regulated genes and found that the GATA transcription factors ELT-3, ELT-5, and ELT-6 are responsible for age regulation of a large fraction of these genes. Expression of elt-5 and elt-6 increases during normal aging, and both of these GATA factors repress expression of elt-3, which shows a corresponding decrease in expression in old worms. elt-3 regulates a large number of downstream genes that change expression in old age, including ugt-9, col-144, and sod-3. elt-5(RNAi) and elt-6(RNAi) worms have extended longevity, indicating that elt-3, elt-5, and elt-6 play an important functional role in the aging process. These results identify a transcriptional circuit that guides the rapid aging process in C. elegans and indicate that this circuit is driven by drift of developmental pathways rather than accumulation of damage.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / genetics
  • Aging / metabolism
  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / metabolism*
  • GATA Transcription Factors / metabolism*
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental*
  • Gene Regulatory Networks
  • Oligonucleotide Array Sequence Analysis

Substances

  • Caenorhabditis elegans Proteins
  • GATA Transcription Factors
  • egl-18 protein, C elegans
  • elt-3 protein, C elegans
  • elt-6 protein, C elegans

Associated data

  • GEO/GSE12094