Aging is associated with a large number of both phenotypic and molecular changes, but for most of these, it is not known whether these changes are detrimental, neutral, or protective. We have identified a conserved Caenorhabditis elegans GATA transcription factor/MTA-1 homolog
egr-1 (
lin-40) that extends lifespan and promotes resistance to heat and UV stress when overexpressed. Expression of
egr-1 increases with age, suggesting that it may promote survival during normal aging. This increase in expression is dependent on the presence of the germline, raising the possibility that
egr-1 expression is regulated by signals from the germline. In addition, loss of
egr-1 suppresses the long lifespan of insulin receptor
daf-2 mutants. The DAF-16 FOXO transcription factor is required for the increased stress resistance of
egr-1 overexpression mutants, and
egr-1 is necessary for the proper regulation of
sod-3 (a reporter for DAF-16 activity). These results indicate that
egr-1 acts within the insulin signaling pathway.
egr-1 can also activate the expression of its paralog
egl-27, another factor known to extend lifespan and increase stress resistance, suggesting that the two genes act in a common program to promote survival. These results identify
egr-1 as part of a longevity-promoting circuit that changes with age in a manner that is beneficial for the lifespan of the organism.