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Hormesis in Caenorhabditis elegans dauer-defective mutants

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Abstract

We have shown that increased longevity and stress resistance can be induced by sub-lethal exposure to stressors (hormesis). Here we ask whether genes of the dauer formation pathway that are known to modulate life span in Caenorhabditis elegans are required for this hormesis. We find that loss-of-function mutations in any of three genes (daf-16,daf-18, or daf-12) not only reduce or abolish the ability to form dauers but also block the hormetic response increasing life span following sub-lethal heat stress. Indeed, the life expectancy of these dauer-defective mutants is decreased by the same pretreatments that increase the life expectancy of wild-type animals. Additionally, we find that daf-16 and daf-12 are not required for the induction of thermotolerance, but daf-18 is required for its full induction. Our results underscore the importance of the dauer-formation pathway in specifying life span by demonstrating a similar, but not identical, role in life extension attributed to hormesis.

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References

  • Anderson GL (1978) Response of dauerlarvae of Caenorhabditis elegans (Nematoda: Rhabditidae) to thermal stress and oxygen deprivation. Can J Zool 56: 1786-1791

    Google Scholar 

  • Anderson GL (1982) Superoxide dismutase activity in dauerlarvae of C. elegans (Nematoda: Rhabditidae). Can J Zool 60: 288-291

    Google Scholar 

  • Antebi A, Yeh W-H, Tait D, Hedgecock EM and Riddle DL (2000) daf-12 encodes a nuclear receptor that regulates the dauer diapause and developmental age in C. elegans. Genes Dev 14: 1512-1527

    PubMed  Google Scholar 

  • Babar P, Adamson C, Walker GA, Walker DW and Lithgow GJ (1999) PI3-kinase inhibition induces dauer formation, thermotolerance and longevity in C. elegans. Neurobiol Aging 20: 513-519

    Article  PubMed  Google Scholar 

  • Barsyte D, Lovejoy DA and Lithgow GJ (2001) Longevity and heavy metal resistance in daf-2 and age-1 long-lived mutants of Caenorhabditis elegans. FASEB J 15: 627-634

    Article  PubMed  Google Scholar 

  • Bartke A (2000) Delayed aging in Ames dwarf mice: Relationships to endocrine function and body size. In: Hekimi S (ed) The Molecular Genetics of Aging, pp 181-202. Springer-Verlag, Heidelberg

    Google Scholar 

  • Bartke A, Coschigano KT, Kopchick JJ, Chandrashekar V, Mattison J, Kinney B and Hauck S (2001) Genes that prolong life: relationships of growth hormone and growth to aging and life span. J Gerontol 56: B340-B349

    Google Scholar 

  • Bluher M, Kahn BB and Kahn CR (2003) Extended longevity in mice lacking the insulin receptor in adipose tissue. Science 299: 572-574

    Article  PubMed  Google Scholar 

  • Braeckman BP, Houthoofd K and Vanfleteren JR (2001) Insulin-like signaling, metabolism, stress resistance and aging in Caenorhabditis elegans. Mech Ageing Dev 122: 673-693

    Article  PubMed  Google Scholar 

  • Butov AA, Johnson TE, Cypser JR, Sannikov IA, Volkov MA, Sehl ME and Yashin AI (2001) Hormesis and debilitation effects in stress experiments using the nematode worm Caenorhabditis elegans: the model of balance between cell damage and HSP levels. Exp Gerontol 37: 57-66

    Article  PubMed  Google Scholar 

  • Calabrese EJ and Baldwin LA (2001) Hormesis: a generalizable and unifying hypothesis. Crit Rev Toxicol 31: 353-424

    Article  PubMed  Google Scholar 

  • Calabrese EJ, Baldwin LA and Holland CD (1999) Hormesis: a highly generalizable and reproducible phenomenon with important implications for risk assessment. Risk Anal 19: 261-281

    Article  PubMed  Google Scholar 

  • Clancy DJ, Gems D, Harshman LG, Oldham S, Stocker H, Hafen E, Leevers SJ and Partridge L (2001) Extension of life-span by loss of CHICO, a Drosophila insulin receptor substrate protein. Science 292: 104-106

    Article  PubMed  Google Scholar 

  • Coschigano KT, Clemmons D, Bellush L and Kopchick JJ (2000) Assessment of growth parameters and life span of GHR/BP gene-disrupted mice. Endocrinology 141: 2608-2613

    Article  PubMed  Google Scholar 

  • Cypser JR and Johnson TE (2002) Multiple stressors in Caenorhabditis elegans induce stress hormesis and extended longevity. J Gerontol 57A: B109-B114

    Google Scholar 

  • Dalley BK and Golomb M (1992) Gene expression in the Caenorhabditis elegans dauer larva: developmental regulation of Hsp90 and other genes. Dev Biol 151: 80-90

    Article  PubMed  Google Scholar 

  • Dorman JB, Albinder B, Shroyer T and Kenyon C (1995) The age-1 and daf-2 genes function in a common pathway to control the life-span of Caenorhabditis elegans. Genetics 141: 1399-1406

    PubMed  Google Scholar 

  • Fabrizio P, Pozza F, Pletcher SD, Gendron CM and Longo VD (2001) Regulation of longevity and stress resistance by Sch9 in yeast. Science 292: 288-290

    Article  PubMed  Google Scholar 

  • Finkel T and Holbrook NJ (2000) Oxidants, oxidative stress and the biology of ageing. Nature 408: 239-247

    PubMed  Google Scholar 

  • Friedman DB and Johnson TE (1988a) A mutation in the age-1 gene in Caenorhabditis elegans lengthens life and reduces hermaphrodite fertility. Genetics 118: 75-86

    PubMed  Google Scholar 

  • Friedman DB and Johnson TE (1988b) Three mutants that extend both mean and maximum life span of the nematode, Caenorhabditis elegans, define the age-1 gene. J Gerontol 43: B102-B109

    PubMed  Google Scholar 

  • Gems D and Riddle DL (2000) Genetic, behavioral, and environmental determinants of male longevity in Caenorhabditis elegans. Genetics 154: 1597-1610

    PubMed  Google Scholar 

  • Gems D, Sutton AJ, Sundermeyer ML, Albert PS, King KV, Edgley ML, Larsen P and Riddle DL (1998) Two pleiotropic classes of daf-2 mutation affect larval arrest, adult behavior, reproduction and longevity in Caenorhabditis elegans. Genetics 150: 129-155

    PubMed  Google Scholar 

  • Gil EB, Malone Link E, Liu LX, Johnson CD and Lees JA (1999) Regulation of the insulin-like developmental pathway of Caenorhabditis elegans by a homolog of the PTEN tumor suppressor gene. Proc Natl Acad Sci USA 96: 2925-2930

    Article  PubMed  Google Scholar 

  • Golden JW and Riddle DL (1984) The Caenorhabditis elegans dauer larva: developmental effects of pheromone, food, and temperature. Dev Biol 102: 368-378

    Article  PubMed  Google Scholar 

  • Guarente L and Kenyon C (2000) Genetic pathways that regulate ageing in model organisms. Nature 408: 255-262

    Article  PubMed  Google Scholar 

  • Harshman LG, Moore KN, Sty MA and Magwire MM (1999) PatStress resistance and longevity in selected lines of Drosophila melanogaster. Neurobiol Aging 20: 521-529

    Article  PubMed  Google Scholar 

  • Henderson S and Johnson TE (2001) daf-16 integrates developmental and environmental inputs to mediate aging in the nematode Caenorhabditis elegans. Curr Biol 11: 1975-1980

    Article  PubMed  Google Scholar 

  • Holzenberger M, Dupont J, Ducos B, Leneuve P, Geloen A, Even PC, Cervera P and Le Bouc Y (2003) IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice. Nature 421: 182-187

    Article  PubMed  Google Scholar 

  • Hsin H and Kenyon C (1999) Signals from the reproductive system regulate the lifespan of C. elegans. Nature 399: 362-366

    Article  PubMed  Google Scholar 

  • Inoue T and Thomas JH (2000) Suppressors of transforming growth factor beta pathway mutants in the Caenorhabditis elegans dauer formation pathway. Genetics 156: 1035-1046

    PubMed  Google Scholar 

  • Jazwinski S (2001) New clues to old yeast. Mech Ageing Dev 122: 865-882

    Article  PubMed  Google Scholar 

  • Johnson TE (1990) Increased life-span of age-1 mutants in C. elegans and lower Gompertz rate of aging. Science 249: 908-912

    PubMed  Google Scholar 

  • Johnson TE and Hartman PS (1988) Radiation effects on life span in Caenorhabditis elegans. J Gerontol 43: B137-B141

    PubMed  Google Scholar 

  • Johnson TE and Wood WB (1982) Genetic analysis of life-span in Caenorhabditis elegans. Proc Natl Acad Sci USA 79: 6603-6607

    PubMed  Google Scholar 

  • Johnson TE, Friedman DB, Foltz N, Fitzpatrick PA and Shoemaker JE (1990) Genetic variants and mutations of Caenorhabditis elegans provide tools for dissecting the aging processes. In: Harrison DE (ed) Genetic Effects on Aging, pp 101-127. Telford Press, New York

    Google Scholar 

  • Johnson TE, de Castro E, de Castro SH, Cypser JR, Henderson S and Tedesco PM (2001a) Relationship between increased longevity and stress resistance as assessed through gerontogene mutations in Caenorhabditis elegans. Exp Gerontol 36: 1609-1617

    Article  PubMed  Google Scholar 

  • Johnson TE, Wu D, Tedesco PM, Dames S and Vaupel JW (2001b) Age-specific demographic profiles of longevity mutants in Caenorhabditis elegans show segmental effects. J Gerontol 56: B331-B339

    Google Scholar 

  • Jones SJM, Riddle DL, Pouzyrev AT, Velcules VE, Hillier L, Eddy SR, Strickli SL, Baillie DL, Waterston R and Marra MA (2001) Changes in gene-expression associated with developmental arrest and longevity in Caenorhabditis elegans. Genome Res 11: 1346-1352

    Article  PubMed  Google Scholar 

  • Kang HL, Benzer S and Min KT (2002) Life extension in Drosophila by feeding a drug. Proc Natl Acad Sci USA 99: 838-843

    Article  PubMed  Google Scholar 

  • Kenyon C, Chang J, Gensch E, Rudner A and Tabtiang R (1993) A C. elegans mutant that lives twice as long as wild type. Nature 366: 461-464

    Article  PubMed  Google Scholar 

  • Khazaeli AA, Tatar M, Pletcher SD and Curtsinger JW (1997) Heat-induced longevity extension in Drosophila. I. Heat treatment, mortality, and thermotolerance. J Gerontol 52A: B48-B52

    Google Scholar 

  • Klass MR (1977) Aging in the nematode Caenorhabditis elegans: major biological and environmental factors influencing life span. Mech Ageing Dev 6: 413-429

    Article  PubMed  Google Scholar 

  • Klass MR (1983) A method for the isolation of longevity mutants in the nematode Caenorhabditis elegans and initial results. Mech Ageing Dev 22: 279-286

    Article  PubMed  Google Scholar 

  • Klass MR and Hirsh D (1976) Nonaging developmental variant of Caenorhabditis elegans. Nature 260: 523-525

    Article  PubMed  Google Scholar 

  • Lakowski B and Hekimi S (1998) The genetics of caloric restriction in Caenorhabditis elegans. Proc Natl Acad Sci USA 95: 13091-13096

    Article  PubMed  Google Scholar 

  • Larsen P (1993) Aging and resistance to oxidative damage in Caenorhabditis elegans. Proc Natl Acad Sci USA 90: 8905-8909

    PubMed  Google Scholar 

  • Larsen P, Albert PS and Riddle DL (1995) Genes that regulate both development and longevity in Caenorhabditis elegans. Genetics 139: 1567-1583

    PubMed  Google Scholar 

  • Lin K, Dorman JB, Rodan A and Kenyon C (1997) daf-16: an HNF-3/forkhead family member that can function to double the life-span of Caenorhabditis elegans. Science 278: 1319-1322

    Article  PubMed  Google Scholar 

  • Lin Y-J, Seroude L and Benzer S (1998) Extended life-span and stress resistance in the Drosophila mutant methuselah. Science 282: 943-946

    Article  PubMed  Google Scholar 

  • Lithgow GJ, White TM, Hinerfeld DA and Johnson TE (1994) Thermotolerance of a long-lived mutant of Caenorhabditis elegans. J Gerontol 49: B270-B276

    PubMed  Google Scholar 

  • Lithgow GJ, White TM, Melov S and Johnson TE (1995) Thermotolerance and extended life-span conferred by single-gene mutations and induced by thermal stress. Proc Natl Acad Sci USA 92: 7540-7544

    PubMed  Google Scholar 

  • Mahajan-Miklos S, Tan M-W, Rahme LG and Ausubel SM (1999) Molecular mechanisms of bacterial virulence elucidated using a Pseudomonas aeruginosa-Caenorhabditis elegans pathogenesis model. Cell 96: 47-56

    Article  PubMed  Google Scholar 

  • Martin GM, Austed SN and Johnson TE (1996) Genetic analysis of ageing: role of oxidative damage and environmental stresses. Nat Genetics 13: 25-34

    Article  Google Scholar 

  • Melov S, Ravenscroft J, Malik S, Gill MS, Walker DW, Clayton PE, Wallace DC, Malfroy B, Doctrow SR and Lithgow GJ (2000) Extension of life-span with superoxide dismutase/catalase mimetics. Science 289: 1567-1569

    Article  PubMed  Google Scholar 

  • Michalski AI, Johnson TE, Cypser JR and Yashin AI (2001) Heating stress patterns in Caenorhabditis elegans longevity and survivorship. Biogerontology 2: 35-44

    Article  PubMed  Google Scholar 

  • Migliaccio E, Giorgio M, Mele S, Pelicci G, Reboldi P, Pandolfi PP, Lanfrancone L and Pelicci PG (1999) The p66shc adaptor protein controls oxidative stress response and life span in mammals. Nature 402: 309-313

    Article  PubMed  Google Scholar 

  • Mihaylova VT, Borland CZ, Manjarrez L, Stern MJ and Sun H (1999) The PTEN tumor suppressor homolog in Caenorhabditis elegans regulates longevity and dauer formation in an insulin receptor-like signaling pathway. Proc Natl Acad Sci USA 96: 7427-7432

    Article  PubMed  Google Scholar 

  • Minois N (2000) Longevity and aging: beneficial effects of exposure to mild stress. Biogerontology 1: 15-29

    Article  PubMed  Google Scholar 

  • Morris JZ, Tissenbaum H and Ruvkun G (1996) A phosphotidylinositol-3-OH kinase family member regulating longevity and diapause in Caenorhabditis elegans. Nature 382: 536-539

    Article  PubMed  Google Scholar 

  • Murakami S and Johnson TE (1996) A genetic pathway conferring life extension and resistance to UV stress in Caenorhabditis elegans. Genetics 143: 1207-1218

    PubMed  Google Scholar 

  • Murakami S and Johnson TE (2001) The OLD-1 positive regulator of longevity and stress resistance is under DAF-16 regulation in Caenorhabditis elegans. Curr Biol 11: 1517-1523

    Article  PubMed  Google Scholar 

  • Ogg S and Ruvkun G (1998) The C. elegans PTEN homolog, DAF-18, acts in the insulin receptor-like metabolic signaling pathway. Mol Cell 2: 887-893

    Article  PubMed  Google Scholar 

  • Ogg S, Paradis S, Gottlieb S, Patterson G, Lee L, Tissenbaum H and Ruvkun G (1997) The fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans. Nature 389: 994-999

    Article  PubMed  Google Scholar 

  • Partridge L and Gems D (2002) The evolution of longevity. Curr Biol 12: R544-R546

    Article  PubMed  Google Scholar 

  • Patterson G, Koweek A, Wong A, Liu Y and Ruvkun G (1997) The DAF-3 Smad protein antagonizes TGF-b-related receptor signaling in the Caenorhabditis elegans dauer pathway. Genes Dev 11: 2679-2690

    PubMed  Google Scholar 

  • Patterson GI and Padgett RW (2000) TGF-beta-related pathways: roles in Caenorhabditis elegans development. Trends Genetics 16: 27-33

    Article  Google Scholar 

  • Peto R and Peto J (1972) Asymptotically efficient rank invariant test procedures. J R Stat Soc A135: 185-198

    Google Scholar 

  • Phillips JP, Parkes TL and Hilliker AJ (2000) Targeted neuronal gene expression and longevity in Drosophila. Exp Gerontol 35: 1157-1164

    Article  PubMed  Google Scholar 

  • Riddle DL and Albert PS (1997) Genetic and environmental regulation of dauer larva development. In: Riddle DL, Blumenthal T, Meyer BJ and Priess JR (eds) C elegans II, pp 739-768. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York

    Google Scholar 

  • Riddle DL, Swanson MM and Albert PS (1981) Interacting genes in nematode dauer larva formation. Nature 290: 668-671

    Article  PubMed  Google Scholar 

  • Rouault JP, Kuwabara PE, Sinilnikova OM, Duret L, Thierry-Mieg D and Billaud M (1999) Regulation of dauer larva development in Caenorhabditis elegans by daf-18, a homologue of the tumour suppressor PTEN. Curr Biol 9(6): 329-332

    Article  PubMed  Google Scholar 

  • Seong KH, Ogashiwa T, Matsuo T, Fuyama Y and Aigaki T (2001) Application of the gene search system to screen for longevity genes in Drosophila. Biogerontology 2: 209-217

    Article  PubMed  Google Scholar 

  • Shama S, Lai C-Y, Antoniazzi JM, Jiang JC and Jazwinski S (1998) Heat stress-induced life span extension in yeast. Exp Cell Res 245: 379-388

    Article  PubMed  Google Scholar 

  • Sulston J and Hodgkin J (1988) The Nematode Caenorhabditis elegans, pp 587-606. Cold Spring Harbor Press, Plainview, New York

    Google Scholar 

  • Sun J and Tower J (1999) FLP recombinase-mediated induction of Cu/Zn-superoxide dismutase transgene expression can extend the life span of adult Drosophila melanogaster flies. Mol Cell Biol 19: 216-228

    PubMed  Google Scholar 

  • Tatar M and Yin C (2001) Slow aging during insect reproductive diapause: why butterflies, grasshoppers and flies are like worms. Exp Gerontol 36: 723-738

    Article  PubMed  Google Scholar 

  • Tatar M, Kopelman A, Epstein D, Tu M-P, Yin C-N and Garofalo RS (2001) A mutant Drosophila insulin receptor homolog that extends life-span and impairs neuroendocrine function. Science 292: 107-110

    Article  PubMed  Google Scholar 

  • Thomas JH, Birnby DA and Vowels JJ (1993) Evidence for parallel processing of sensory information controlling dauer formation in Caenorhabditis elegans. Genetics 134: 1105-1117

    PubMed  Google Scholar 

  • Vanfleteren JR (1993) Oxidative stress and ageing in Caenorhabditis elegans. Biochem J 292: 605-608

    PubMed  Google Scholar 

  • Vettraino J, Buck S and Arking R (2001) Direct selection for paraquat resistance in Drosophila results in a different extended longevity phenotype. J Gerontol 56: B415-B425.

    Google Scholar 

  • Walker GA, Walker DW and Lithgow GJ (1998a) Genes that determine both thermotolerance and rate of aging in Caenorhabditis elegans. Ann N Y Acad Sci 851: 444-449

    PubMed  Google Scholar 

  • Walker GA, Walker DW and Lithgow GJ (1998b) A relationship between thermotolerance and longevity in Caenorhabditis elegans. J Invest Dermatol 3: 6-10

    Google Scholar 

  • Walker GA, White TM, McColl G, Jenkins NL, Babisch S, Candido EPM, Johnson TE and Lithgow GJ (2001) Heat shock protein accumulation is upregulated in a long-lived mutant of Caenorhabditis elegans. J Gerontol A Biol Sci Med Sci 56: B281-B287.

    PubMed  Google Scholar 

  • Weindruch R and Walford RL (1988) The Retardation of Aging and Disease by Dietary Restriction. Charles C. Thomas, Springfield, Illinois

    Google Scholar 

  • Yashin AI, Cypser JR, Johnson TE, Michalski AI, Boyko SI and Novoseltsev VN (2001) Ageing and survival after different doses of heat shock: the results of analysis of data from stress experiments with the nematode worm Caenorhabditis elegans. Mech Ageing Dev 122: 1477-1495

    Article  PubMed  Google Scholar 

  • Yashin AI, Cypser JR, Johnson TE, Michalski AI, Boyko SI and Novoseltsev VN (2002) Heat shock changes the heterogeneity distribution in populations of Caenorhabditis elegans: does it tell us anything about the biological mechanism of stress response? J Gerontol 57A: B83-B92

    Google Scholar 

  • Yokoyama K, Fukumoto K, Murakami T, Harada S, Hosono R, Wadhwa R, Mitsui Y and Ohkuma S (2002) Extended longevity of Caenorhabditis elegans by knocking in extra copies of hsp70F, a homolog of mot-2 (mortalin)/mthsp70/Grp75. FEBS Lett 516: 53-57

    Article  PubMed  Google Scholar 

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  1. James R. Cypser

    Present address: Department of Ecology and Evolutionary Biology, Brown University, Providence, RI, 02912, USA

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  1. Institute for Behavioral Genetics, University of Colorado, Box 447, Boulder, CO, 80309, USA

    James R. Cypser & Thomas E. Johnson

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Cypser, J.R., Johnson, T.E. Hormesis in Caenorhabditis elegans dauer-defective mutants. Biogerontology 4, 203–214 (2003). https://doi.org/10.1023/A:1025138800672

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