Authors: Budovskaya YV; Wu K; Southworth LK; Jiang M; Tedesco P; Johnson TE; Kim SK
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.Keywords: Aging/genetics/metabolism; Animals; Caenorhabditis elegans/genetics/*physiology; Caenorhabditis elegans Proteins/*metabolism; GATA Transcription Factors/*metabolism; Gene Expression Profiling; *Gene Expression Regulation, Developmental; Gene Regulatory Networks; Oligonucleotide Array Sequence Analysis
Date: July 30, 2008
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Budovskaya YV, Wu K, Southworth LK, Jiang M, Tedesco P, Johnson TE, Kim SK (2008) An elt-3/elt-5/elt-6 GATA transcription circuit guides aging in C. elegans. Cell 134: 291-303.