Lifespan Modulation By TRPA-1 Via Immune Signals In C.elegans

There are a variety of factors affecting aging,and it is of great scientific and practical significance to understand aging and its mechanisms.Caenorhabditis elegans is a soil-free nematode.It usually feeds on Escherichia coli OP50 under the laboratory conditions.Its short life cycle,large number of progeny and completed whole genome sequence make C.elegans a classic model animal for studying aging and its mechanisms.It has been reported that temperature has an important effect on aging.Our previous studies have shown that TRPA-1 is a temperature-sensitive receptor in C.elegans,which regulates the lifespan of C.elegans in a temperature dependent manner.TRPA-1 does not have an obvious effect on C.elegans lifespan at high temperatures;while TRPA-1 in the intestine and neurons are activated to extend the lifespan of C.elegans at low temperatures through downstream signaling factors.Here,our research found that TRPA-1 regulated the lifespan of C.elegans,which was related to the food they ingest.Feeding C.elegans with live bacteria at low temperature could activate TRPA-1 and prolong its lifespan,while TRPA-1 could not significantly prolong the lifespan of C.elegans fed with UV-killed bacteria.In addition,we also found that TRPA-1 was not able to change the lifespan of C.elegans on either live bacteria or UV-killed bacteria at high temperature.Further studies found that intestinal TRPA-1,but not neuronal TRPA-1,was involved in this unique longevity regulation process.Next,through RNA interference technology,we found that DBL-1 and DAF-16 participated in the life regulation of TRPA-1 in response to different temperature,but not to different diet(live vs dead diet).Our further analysis found that knocking down some key molecules of classic immune signaling pathways,such as PMK-1,MPK-1,KGB-1 and JNK-1,did not affect the longevity modulation by TRPA-1.In addition,via real-time quantitative PCR and in vivo fluorescent microscopy imaging,we figured out that the expression level changes of 9 immune signal-related factors(IRG-1,IRG-2,LYS-1,CLEC-67,MUL-1,K08D8.5,GST-4,F35E12.5 and SOD-3)in response to different diet(live vs dead diet)did not dependent on TRPA-1,which indicated that the relevant immune signaling pathways were most likely not necessary for longevity modulation in response to different diet by TRPA-1.Thus,we had found that those 15 immune factors were not required for TRPA-1 to modulate the lifespan of C.elegans in response to different diet(live vs dead diet).As those 15 immune factors are involved in almost all known immune signaling pathways in C.elegans,so we could draw a conclusion: known immune response signaling pathways/factors are not required for TRPA-1 to regulate the lifespan of C.elegans in diet(live or dead)dependent manner at low temperature.