Lifespan and dauer arrest in C. elegans are controlled by the
daf-2 /insulin-like signaling pathway. In adults, mutations in
daf-2 , an insulin/IGF-I receptor homolog, or
age-1 , a homolog of the
p110 catalytic subunit of PI(3)K, significantly extend lifespan. In addition, null mutations in these genes cause constitutive arrest as dauer larvae. Previously, we showed that the long lifespan of
daf-2 and
age-1 mutants is rescued by restoring
daf-2 or
age-1 activity to neurons. In addition, dauer arrest in these mutants is rescued by
daf-2 or
age-1 expression in either neuronal or non-neuronal cell types, although rescue from neurons was most potent. To identify specific neurons that control dauer arrest and lifespan, we have expressed an
age-1 cDNA from several neuronal subtype-specific promoters in
age-1 null mutants. Expressing
age-1 from the promoters for
mec-7 (mechanosensory neurons),
unc-4 (motor neurons) or
osm-3 (chemosensory neurons) can rescue
age-1(0) dauer arrest, but not lifespan. This suggests that
daf-2 pathway signaling in these cell types is not sufficient for wild-type lifespan. We are currently investigating whether wild-type lifespan requires
age-1 activity in other neurons, or in combinations of neurons. The
daf-2 pathway controls lifespan and dauer arrest non-cell autonomously from neurons, suggesting that the
daf-2 pathway may regulate downstream genes for dauer remodeling and aging of target cells. To identify these genes, we screened for mutations that revert the ability of the neuronally-expressed
unc-14 promoter ::
age-1 transgene to rescue dauer arrest in
age-1 null mutants. This screen is predicted to identify mutations in genes that are required for signaling from the neuronal
daf-2 pathway to the target cells that are remodeled during dauer morphogenesis, such as the pharynx, hypodermis, gonad and intestine. In addition, these genes may act in the
daf-2 lifespan pathway. We are currently mapping and characterizing the mutants we identified in this screen.