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. 2010 Apr 8;26(2):91–103. doi: 10.1007/s12264-010-0162-6

Genes required for the functions of olfactory AWA neuron regulate the longevity of Caenorhabditis elegans in an insulin/IGF signaling-dependent fashion

嗅觉神经元AWA功能必需基因以胰岛素信号依赖的方式调控秀丽线虫的衰老

Lu-Lu Shen 1, Min Du 1, Xing-Feng Lin 1, Ting Cai 1, Da-Yong Wang 1,✉
PMCID: PMC5552603  PMID: 20332814

Abstract

Objective

To investigate the interaction between the genes required for the functions of AWA olfactory neuron and insulin/IGF signaling in regulating the longevity of nematode Caenorhabditis elegans (C. elegans).

Methods

The mutants that had loss-of-function mutation of the genes required for AWA, AWC, ASE, and AFD sensory neurons were employed. Lifespan, the speed of pharynx pumping, the intestinal autofluorescence, the dauer formation, and the brood size were examined. Rescue experiments were performed to confirm the role of the genes required for the functions of AWA neuron in regulating lifespan. Moreover, genetic interactions between genes required for the functions of AWA neuron and insulin/IGF signaling were investigated.

Results

Mutations of odr-7, odr-2, and odr-3 genes required for the functions of AWA neuron significantly increased the mean lifespan of nematodes and slowed the accumulation of intestinal autofluorescence. Besides, these mutations were closely associated with higher pumping rates during aging. However, mutation of odr-7, odr-2, or odr-3 did not obviously affect the brood size or the dauer formation, and the regulation of longevity by odr-7, odr-2, and odr-3 was temperature-independent. In contrast, mutations of genes required for the functions of ASE, AWC, and AFD sensory neurons did not influence the nematode lifespan. Moreover, expression of odr-7, odr-2 and odr-3 in AWA neuron could completely or largely restore the altered lifespan in odr-7, odr-2 and odr-3 mutants. Furthermore, genetic interaction assay demonstrated that the extended lifespan in odr-7 mutant could be suppressed by daf-16 mutation and enhanced by daf-2 or age-1 mutation, whereas mev-1 and pha-4 were not required for the long lifespan of odr-7 mutant.

Conclusion

The genes required for the function of AWA sensory neuron could regulate the nematode longevity in an insulin/IGF signaling-dependent fashion in C. elegans.

Keywords: longevity, ODR-7, AWA olfactory neuron, insulin/IGF signaling, genetic interaction, C. elegans

References

  • [1].Klass M.R. Aging in the nematode Caenorhabditis elegans: major biological and environmental factors influencing life span. Mech Ageing Dev. 1977;6:413–429. doi: 10.1016/0047-6374(77)90043-4. [DOI] [PubMed] [Google Scholar]
  • [2].Braeckman B.P., Vanfleteren J.R. Genetic control of longevity in C. elegans. Exp Gerontol. 2007;42:90–98. doi: 10.1016/j.exger.2006.04.010. [DOI] [PubMed] [Google Scholar]
  • [3].Shen L.L., Wang Y., Wang D.Y. Involvement of genes required for synaptic function in aging control in C. elegans. Neurosci Bull. 2007;23:21–29. doi: 10.1007/s12264-007-0003-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [4].Wolkow C.A., Kimura K.D., Lee M., Ruvkun G. Regulation of C. elegans life-span by insulinlike signaling in the nervous system. Science. 2000;290:147–150. doi: 10.1126/science.290.5489.147. [DOI] [PubMed] [Google Scholar]
  • [5].Apfeld J., Kenyon C. Regulation of lifespan by sensory perception in Caenorhabditis elegans. Nature. 1999;402:804–809. doi: 10.1038/45544. [DOI] [PubMed] [Google Scholar]
  • [6].White J.G., Southgate E., Thomson J.N., Brenner S. The structure of the nervous system of the nematode C. elegans. Phil Trans R Soc Lond B. 1986;314:1–340. doi: 10.1098/rstb.1986.0056. [DOI] [PubMed] [Google Scholar]
  • [7].Mori I., Ohshima Y. Molecular neurogenetics of chemotaxis and thermotaxis in the nematode Caenorhabditis elegans. BioEssays. 1997;19:1055–1064. doi: 10.1002/bies.950191204. [DOI] [PubMed] [Google Scholar]
  • [8].Hu Y.O., Sun Y., Ye B.P., Wang D.Y. Computational analysis of genetic loci required for amphid structure and functions and their possibly corresponding microRNAs in C. elegans. Neurosci Bull. 2007;23:9–20. doi: 10.1007/s12264-007-0002-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [9].Fujii M., Matsumoto Y., Tanaka N., Miki K., Suzuki T., Ishii N., et al. Mutations in chemosensory cilia cause resistance to paraquat in nematode Caenorhabditis elegans. J Biol Chem. 2004;279:20277–20282. doi: 10.1074/jbc.M313119200. [DOI] [PubMed] [Google Scholar]
  • [10].Alcedo J., Kenyon C. Regulation of C. elegans longevity by specific gustatory and olfactory neurons. Neuron. 2004;41:45–55. doi: 10.1016/S0896-6273(03)00816-X. [DOI] [PubMed] [Google Scholar]
  • [11].Brenner S. The genetics of Caenorhabditis elegans. Genetics. 1974;77:71–94. doi: 10.1093/genetics/77.1.71. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [12].Donkin S., Williams P.L. Influence of developmental stage, salts and food presence on various end points using Caenorhabditis elegans for aquatic toxicity testing. Environ Appl Toxicol. 1995;14:2139–2147. [Google Scholar]
  • [13].Wilson M.A., Shukitt-Hale B., Kalt W., Ingram D.K., Joseph J.A., Wolkow C.A. Blueberry polyphenols increase lifespan and thermotolerance in Caenorhabditis elegans. Aging Cell. 2006;5:59–68. doi: 10.1111/j.1474-9726.2006.00192.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [14].Huang C., Xiong C., Kornfeld K. Measurements of age-related changes of physiological processes that predict lifespan of Caenorhabditis elegans. Proc Natl Acad Sci U S A. 2004;101:8084–8089. doi: 10.1073/pnas.0400848101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [15].Rui Q., Lu Q., Wang D.Y. Administration of Bushenkangshuai Tang alleviates the UV irradiation- and oxidative stress-induced lifespan defects in nematode Caenorhabditis elegans. Front Med China. 2009;3:76–90. doi: 10.1007/s11684-009-0002-0. [DOI] [Google Scholar]
  • [16].Garigan D., Hsu A.L., Fraser A.G., Kamath R.S., Ahringer J., Kenyon C. Genetic analysis of tissue aging in Caenorhabditis elegans: a role for heat-shock factor and bacterial proliferation. Genetics. 2002;161:1101–1112. doi: 10.1093/genetics/161.3.1101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [17].Boehm M., Slack F.A. A developmental timing microRNA and its target regulate life span in C. elegans. Science. 2005;310:1954–1957. doi: 10.1126/science.1115596. [DOI] [PubMed] [Google Scholar]
  • [18].Wang X.Y., Shen L.L., Yu H.X., Wang D.Y. Toxicity evaluation in a paper recycling mill effluent by coupling bioindicator of aging with the toxicity identification evaluation method in nematode Caenorhabditis elegans. J Environ Sci. 2008;20:1373–1380. doi: 10.1016/S1001-0742(08)62235-4. [DOI] [PubMed] [Google Scholar]
  • [19].Guo Y.L., Yang Y.C., Wang D.Y. Induction of reproductive deficits in nematode Caenorhabditis elegans exposed to metals at different developmental stages. Reprod Toxicol. 2009;28:90–95. doi: 10.1016/j.reprotox.2009.03.007. [DOI] [PubMed] [Google Scholar]
  • [20].Xiao J., Rui Q., Guo Y.L., Chang X.Y., Wang D.Y. Prolonged manganese exposure induces severe deficits in lifespan, development and reproduction possibly by altering oxidative stress response in Caenorhabditis elegans. J Environ Sci. 2009;21:842–848. doi: 10.1016/S1001-0742(08)62350-5. [DOI] [PubMed] [Google Scholar]
  • [21].Mello C.C., Kramer J.M., Stinchcomb D., Ambros V. Efficient gene transfer in C. elegans: extrachromosomal maintenance and integration of transforming sequence. EMBO J. 1991;10:3959–3970. doi: 10.1002/j.1460-2075.1991.tb04966.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [22].Wang D.Y., Wang Y. HLB-1 functions as a new regulator for the organization and function of neuromuscular junctions in nematode Caenorhabditis elegans. Neurosci Bull. 2009;25:75–86. doi: 10.1007/s12264-009-0119-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [23].Sengupta P., Colbert H.A., Bargmann C.I. The C. elegans gene odr-7 encodes an olfactory-specific member of the nuclear receptor superfamily. Cell. 1994;79:971–980. doi: 10.1016/0092-8674(94)90028-0. [DOI] [PubMed] [Google Scholar]
  • [24].Sengupta P., Chou J.H., Bargmann C.I. odr-10 encodes a seven transmembrane domain olfactory receptor required for responses to the odorant diacetyl. Cell. 1996;84:899–909. doi: 10.1016/S0092-8674(00)81068-5. [DOI] [PubMed] [Google Scholar]
  • [25].Roayaie K., Crump J.G., Sagasti A., Bargmann C.I. The Gα protein ODR-3 mediates olfactory and nociceptive function and controls cilium morphogenesis in C. elegans olfactory neurons. Neuron. 1998;20:55–67. doi: 10.1016/S0896-6273(00)80434-1. [DOI] [PubMed] [Google Scholar]
  • [26].Chou J.H., Bargmann C.I., Sengupta P. The Caenorhabditis elegans odr-2 gene encodes a novel Ly-6-related protein required for olfaction. Genetics. 2001;157:211–224. doi: 10.1093/genetics/157.1.211. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [27].Uchida O., Nakano H., Koga M., Ohshima Y. The C. elegans che-1 gene encodes a zinc finger transcription factor required for specification of the ASE chemosensory neurons. Development. 2001;130:1215–1224. doi: 10.1242/dev.00341. [DOI] [PubMed] [Google Scholar]
  • [28].Chang S., Johnson R.J., Jr, Frokjaer-Jensen C., Lockery S., Hobert O. MicroRNAs act sequentially and asymmetrically to control chemosensory laterality in the nematode. Nature. 2004;430:785–789. doi: 10.1038/nature02752. [DOI] [PubMed] [Google Scholar]
  • [29].Satterlee J.S., Sasakura H., Kuhara A., Berkeley M., Mori I., Sengupta P. Specification of thermosensory neuron fate in C. elegans requires ttx-1, a homolog of otd/Otx. Neuron. 2001;31:943–956. doi: 10.1016/S0896-6273(01)00431-7. [DOI] [PubMed] [Google Scholar]
  • [30].L’Etoile N.D., Bargmann C.I. Olfaction and odor discrimination are mediated by the C. elegans guanylyl cyclase ODR-1. Neuron. 2000;25:575–586. doi: 10.1016/S0896-6273(00)81061-2. [DOI] [PubMed] [Google Scholar]
  • [31].Vowels J.J., Thomas J.H. Multiple chemosensory defects in daf-11 and daf-21 mutants of Caenorhabditis elegans. Genetics. 1994;138:303–316. doi: 10.1093/genetics/138.2.303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [32].Inoue T., Thomas J.H. Suppressors of transforming growth factor-â pathway mutants in the Caenorhabditis elegans dauer formation pathway. Genetics. 2000;156:1035–1046. doi: 10.1093/genetics/156.3.1035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [33].Simmer F., Moorman C., van der Linden A.M., Kuijk E., van der Berghe P.V., Kamath R.S., et al. Genome-wide RNAi of C. elegans using the hypersensitive rrf-3 strain reveals novel gene functions. PLoS Biol. 2003;1:e12. doi: 10.1371/journal.pbio.0000012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [34].Kenyon C., Chang J., Gensch E., Rudner A., Tabtiang R. C. elegans mutant that lives twice as long as wild type. Nature. 1993;366:461–464. doi: 10.1038/366461a0. [DOI] [PubMed] [Google Scholar]
  • [35].Ogg S., Paradis S., Gottlieb S., Patterson G.I., Lee L., Tissenbaum H.A., et al. The fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans. Nature. 1997;389:994–999. doi: 10.1038/40194. [DOI] [PubMed] [Google Scholar]
  • [36].Lin K., Dorman J.B., Rodan A., Kenyon C. daf-16: an HNF-3/forkhead family member that can function to double the lifespan of Caenorhabditis elegans. Science. 1997;278:1319–1322. doi: 10.1126/science.278.5341.1319. [DOI] [PubMed] [Google Scholar]
  • [37].Murphy C.T., McCarroll S.A., Bargmann C.I., Fraser A., Kamath R.S., Ahringer J., et al. Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans. Nature. 2003;424:277–284. doi: 10.1038/nature01789. [DOI] [PubMed] [Google Scholar]
  • [38].Ishii N., Fujii M., Hartman P.S., Tsuda M., Yasuda K., Senoo-Matsuda N., et al. A mutation in succinate dehydrogenase cytochrome b causes oxidative stress and ageing in nematodes. Nature. 1998;394:694–697. doi: 10.1038/29331. [DOI] [PubMed] [Google Scholar]
  • [39].Panowski S.H., Wolff S., Aguilaniu H., Durieux J., Dillin A. PHA-4/Foxa mediates diet-restriction-induced longevity of C. elegans. Nature. 2007;447:550–556. doi: 10.1038/nature05837. [DOI] [PubMed] [Google Scholar]
  • [40].Kimura K.D., Tissenbaum H.A., Liu Y., Ruvkun G. daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans. Science. 1997;277:942–946. doi: 10.1126/science.277.5328.942. [DOI] [PubMed] [Google Scholar]
  • [41].Morris J.Z., Tissenbaum H.A., Ruvkun G. A phosphatidylinositol-3-OH kinase family member regulating longevity and diapause in Caenorhabditis elegans. Nature. 1996;382:536–539. doi: 10.1038/382536a0. [DOI] [PubMed] [Google Scholar]
  • [42].Gems D., Sutton A.J., Sundermeyer M.L., Albert P.S., King K.V., Eddley M.L., et al. Two pleiotropic classes of daf-2 mutations affect larval arrest, adult behavior, reproduction and longevity in Caenorhabditis elegans. Genetics. 1998;150:129–155. doi: 10.1093/genetics/150.1.129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [43].Sampayo J.N., Olsen A., Lithgow G.J. Oxidative stress in Caenorhabditis elegans: protective effects of superoxide dismutase/catalase mimetics. Aging Cell. 2003;2:319–326. doi: 10.1046/j.1474-9728.2003.00063.x. [DOI] [PubMed] [Google Scholar]
  • [44].Mukhopadhyay A., Deplancke B., Walhout A.J.M., Tissenbaum H.A. C. elegans tubby regulates life span and fat storage by two independent mechanisms. Cell Metab. 2005;2:35–42. doi: 10.1016/j.cmet.2005.06.004. [DOI] [PubMed] [Google Scholar]

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