An elt-3/elt-5/elt-6 GATA transcription circuit guides aging in C. elegans.
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An elt-3/elt-5/elt-6 GATA transcription circuit guides aging in C.
elegans.Budovskaya YV, Wu K, Southworth LK, Jiang M, Tedesco P,
Johnson TE, Kim SK.
Department of Developmental Biology, Stanford University Medical
Center, Stanford, CA 94305, USA.
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.
PMID: 18662544 [PubMed - indexed for MEDLINE]