An elt-3/elt-5/elt-6 GATA Transcription Circuit Guides Aging in C. elegans

• Published in: Cell Vol. 134; no. 2; pp. 291 - 303
• Main Authors: Budovskaya, Yelena V., Wu, Kendall, Southworth, Lucinda K., Jiang, Min, Tedesco, Patricia, Johnson, Thomas E., Kim, Stuart K.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 25-07-2008
• Subjects: Aging - genetics; Aging - metabolism; Animals; Caenorhabditis elegans - genetics; Caenorhabditis elegans - physiology; Caenorhabditis elegans Proteins - metabolism; CELLBIO; GATA Transcription Factors - metabolism; Gene Expression Profiling; Gene Expression Regulation, Developmental; Gene Regulatory Networks; HUMDISEASE; Oligonucleotide Array Sequence Analysis; RNA; CELLBIO; RNA; HUMDISEASE
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2008.05.044

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.