Neurosecretory control of aging in Caenorhabditis elegans

Abstract

In the nematode Caenorhabditis elegans, an insulin receptor signaling pathway regulates adult life span and developmental arrest at the dauer larval stage. Here we show that the unc-64 and unc-31 genes also function in this pathway. These two genes are involved in mediating Ca2+-regulated secretion. Mutations in unc-64 and unc-31 increase adult life span and cause constitutive dauer formation. Both phenotypes are suppressed by mutations in daf-16, which also suppresses other mutations in this pathway. We present evidence that the site of action of unc-64 is neuronal, suggesting that a neurosecretory signal regulates life span and dauer formation.

Figure 1

unc-64 and unc-31 mutants have increased life spans and are suppressed by daf-16. Assays were performed at 20°. unc-64 and unc-31 have significantly longer life spans than N2 (P < 0.0001 for unc-64 and P = 0.0004 for unc-31). This figure uses the same data set as Table 1.

Figure 2

Mutations in unc-64 and unc-31 do not enhance the longevity of daf-2 mutants. Animals were grown at 15° to allow development past the dauer stage and then were shifted to 20°. unc-64; unc-31 had a significantly longer life span than either unc-64 (P = 0.0002) or unc-31 (P = 0.0005). The daf-2 unc-64 double mutant and daf-2 were not significantly different (P = 0.5139). The maximum life span of daf-2 unc-64 was extended to >100 days by a single animal. We have not investigated whether this has any possible significance. This figure uses the same data set as Table 2.