An elt-3/elt-5/elt-6 GATA transcription circuit guides aging in C. elegans.
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.
Budovskaya
Yelena V
YV
Department of Developmental Biology, Stanford University Medical Center, Stanford, CA 94305, USA.
Wu
Kendall
K
Southworth
Lucinda K
LK
Jiang
Min
M
Tedesco
Patricia
P
Johnson
Thomas E
TE
Kim
Stuart K
SK
D000375:Aging / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D050980:GATA Transcription Factors / Q000378:metabolism*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D020411:Oligonucleotide Array Sequence Analysis
D029742:Caenorhabditis elegans Proteins; D050980:GATA Transcription Factors; C434745:egl-18 protein, C elegans; C118721:elt-3 protein, C elegans; C434746:elt-6 protein, C elegans