Figure 1.

Crossed signals? During development, the elt-3/elt-5/elt-6 transcriptional circuit guides cell-fate determination in the hypodermis. During adulthood, however, ELT-3 activity appears necessary for stress responses (and for the lifespan-prolonging effects of dietary restriction), and is repressed by insulin/IFG-I-like signaling. As individual C. elegans age, however, expression of elt-5 and elt-6 drifts upward. This drift reduces lifespan by decreasing the levels of ELT-3.