Recent studies reveal a role of fatty acid metabolism in ageing. Oleic acid synthesis influences longevity in the gonadal pathway and polyunsaturated fatty acids (PUFA) have the potential to regulate insulin/IGF-1 signal (IIS). However, the function of fatty acids in ageing is poorly understood. Prostaglandins (PGs) are known as local hormones synthesized from PUFA, which are involved in inflammation and thermogenesis in mammals. Milller and colleagues recently showed that PGs contribute to sperm guidance in worms. We hypothesized that PGs can act as signaling molecules downstream of PUFA metabolism and influence IIS. Several homologs of PG synthase are present in worms: gst family, PGDS; R11A8.5, a PGES-2; ZC395.10, a
p23/PGES-3; and the aldo-keto reductase family, PGFS. To begin a functional analysis, we first looked into dauer formation of mutants of the various homologs. We found that
p23(ok3052) potently formed dauer at 27 deg C, whereas the other mutants did not. We then performed epistasis analysis to investigate how
p23 regulates dauer formation. We found that the Daf-c phenotype of
p23(ok3052) was suppressed by Daf-d mutants in
daf-10(sensory neuron),
daf-12(steroid signal) and
daf-16(IIS) mutations, but not
daf-5(TGF-b).
p23 is also known as a co-chaperone of HSP-90, which is encoded by the worm
daf-21 gene. It was previously shown that
daf-21(
p673) is Daf-c, and work at a similar step in dauer neurosensory processing as
daf-11/guanylyl cyclase. It was revealed that dauer formation of both
daf-11(
m47) and
daf-21(
p673) is suppressed with
daf-10,
daf-12 and
daf-16 mutations, and by cGMP treatment. We thus hypothesized that
p23 works in a complex with
daf-21, to regulate dauer neurosensory processing either through its activity as a PGES-3 or as a chaperone complex. To test this hypothesis, we next analyzed interactions between
p23,
daf-21 and cGMP signal. Surprisingly, cGMP did not rescue the Daf-c phenotypes of
p23(ok3052). We also performed the dauer formation assay with double mutants. We found that
p23(ok3052) modestly enhanced dauer formation of
daf-21(
p673). Unexpectedly, mutations of
pges-2 and
gst-4 enhanced
daf-21 dauer formation more strongly than
p23;
daf-21. These results suggest that
p23 regulates dauer but not via cGMP signal, and that
pges-2 and
gst-4 might have an unknown associated function with
daf-21 upstream of cGMP signal pathways. Finally, we analyzed longevity in these mutants. No significant changes were observed in any mutants at 20 deg C, whereas
p23 and
pges-2 mutants were significantly short lived at 15 deg C. We speculate that PGs signal has an unknown function in thermosensory neurons, and could be involved in ageing due to temperature adaptation mechanisms.