Advertisement

Genes and Pathways That Influence Longevity in Caenorhabditis elegans

  • Yujin Lee
  • Seon Woo A. An
  • Murat Artan
  • Mihwa Seo
  • Ara B. Hwang
  • Dae-Eun Jeong
  • Heehwa G. Son
  • Wooseon Hwang
  • Dongyeop Lee
  • Keunhee Seo
  • Ozlem Altintas
  • Sangsoon Park
  • Seung-Jae V. LeeEmail author

Abstract

The roundworm Caenorhabditis elegans is one of the most popular model organisms for research on aging because of its short lifespan and genetic tractability. Studies using C. elegans have identified many genes and pathways that regulate aging, several of which are conserved in other species, including mammals. In this chapter, we describe longevity-regulatory pathways including insulin/IGF-1 (insulin-like growth factor 1) signaling, TOR (target of rapamycin) signaling, autophagy, mitochondrial respiration, and HIF-1 (hypoxia-inducible factor 1) pathways. We also review the effects of dietary restriction, a key environmental factor that influences aging, on longevity-regulatory genetic factors. In addition, we illustrate the roles of two important C. elegans tissues, those of the sensory neural and reproductive systems, in regulating longevity at the molecular level. For each of the subtopics, we explain how changes in the expression of genes involved in each pathway and system alter longevity. We also speculate on the evolutionary significance of the genes and pathways that affect longevity. Given the conserved nature of longevity regulation, the dissection of the roles of these genetic factors in determining the C. elegans lifespan will provide important clues for understanding the secrets of human aging.

Keywords

C. elegans Aging Insulin/IGF-1 Target of rapamycin Dietary restriction Autophagy Hypoxia-inducible factor Mitochondria Sensory neurons Reproductive system 

References

  1. Ailion M, Inoue T, Weaver CI, Holdcraft RW, Thomas JH (1999) Neurosecretory control of aging in Caenorhabditis elegans. Proc Natl Acad Sci U S A 96(13):7394–7397PubMedCentralPubMedCrossRefGoogle Scholar
  2. Alam H, Williams TW, Dumas KJ, Guo C, Yoshina S, Mitani S, Hu PJ (2010) EAK-7 controls development and life span by regulating nuclear DAF-16/FoxO activity. Cell Metab 12(1):30–41. doi: 10.1016/j.cmet.2010.05.004 PubMedCentralPubMedCrossRefGoogle Scholar
  3. Alcedo J, Kenyon C (2004) Regulation of C. elegans longevity by specific gustatory and olfactory neurons. Neuron 41(1):45–55PubMedCrossRefGoogle Scholar
  4. Antebi A, Yeh WH, Tait D, Hedgecock EM, Riddle DL (2000) daf-12 encodes a nuclear receptor that regulates the Dauer diapause and developmental age in C. elegans. Genes Dev 14(12):1512–1527PubMedCentralPubMedGoogle Scholar
  5. Apfeld J, Kenyon C (1999) Regulation of lifespan by sensory perception in Caenorhabditis elegans. Nature 402(6763):804–809. doi: 10.1038/45544 PubMedCrossRefGoogle Scholar
  6. Apfeld J, O'Connor G, McDonagh T, DiStefano PS, Curtis R (2004) The AMP-activated protein kinase AAK-2 links energy levels and insulin-like signals to lifespan in C. elegans. Genes Dev 18(24):3004–3009PubMedCentralPubMedCrossRefGoogle Scholar
  7. Araiz C, Château MT, Galas S (2008) 14-3-3 regulates life span by both DAF-16-dependent and-independent mechanisms in Caenorhabditis elegans. Exp Gerontol 43(6):505–519. doi: 10.1016/j.exger.2008.03.001 PubMedCrossRefGoogle Scholar
  8. Arantes-Oliveira N, Apfeld J, Dillin A, Kenyon C (2002) Regulation of life-span by germ-line stem cells in Caenorhabditis elegans. Science 295(5554):502–505. doi: 10.1126/science.1065768 PubMedCrossRefGoogle Scholar
  9. Baker BM, Nargund AM, Sun T, Haynes CM (2012) Protective coupling of mitochondrial function and protein synthesis via the eIF2alpha kinase GCN-2. PLoS Genet 8(6), e1002760. doi: 10.1371/journal.pgen.1002760 PubMedCentralPubMedCrossRefGoogle Scholar
  10. Baruah A, Chang H, Hall M, Yuan J, Gordon S, Johnson E, Shtessel LL, Yee C, Hekimi S, Derry WB, Lee SS (2014) CEP-1, the Caenorhabditis elegans p53 homolog, mediates opposing longevity outcomes in mitochondrial electron transport chain mutants. PLoS Genet 10(2), e1004097. doi: 10.1371/journal.pgen.1004097 PubMedCentralPubMedCrossRefGoogle Scholar
  11. Bennett CF, Vander Wende H, Simko M, Klum S, Barfield S, Choi H, Pineda VV, Kaeberlein M (2014) Activation of the mitochondrial unfolded protein response does not predict longevity in Caenorhabditis elegans. Nat Commun 5:3483. doi: 10.1038/ncomms4483 PubMedCentralPubMedCrossRefGoogle Scholar
  12. Berdichevsky A, Viswanathan M, Horvitz HR, Guarente L (2006) C. elegans SIR-2.1 interacts with 14-3-3 proteins to activate DAF-16 and extend life span. Cell 125(6):1165–1177. doi: 10.1016/j.cell.2006.04.036 PubMedCrossRefGoogle Scholar
  13. Berman JR, Kenyon C (2006) Germ-cell loss extends C. elegans life span through regulation of DAF-16 by kri-1 and lipophilic-hormone signaling. Cell 124(5):1055–1068. doi: 10.1016/j.cell.2006.01.039 PubMedCrossRefGoogle Scholar
  14. Bishop NA, Guarente L (2007) Two neurons mediate diet-restriction-induced longevity in C. elegans. Nature 447(7144):545–549. doi: 10.1038/nature05904 PubMedCrossRefGoogle Scholar
  15. Boehm M, Slack F (2005) A developmental timing microRNA and its target regulate life span in C. elegans. Science 310(5756):1954–1957. doi: 10.1126/science.1115596 PubMedCrossRefGoogle Scholar
  16. Boulias K, Horvitz HR (2012) The C. elegans microRNA mir-71 acts in neurons to promote germline-mediated longevity through regulation of DAF-16/FOXO. Cell Metab 15(4):439–450. doi: 10.1016/j.cmet.2012.02.014 PubMedCentralPubMedCrossRefGoogle Scholar
  17. Braeckman BP, Houthoofd K, De Vreese A, Vanfleteren JR (1999) Apparent uncoupling of energy production and consumption in long-lived Clk mutants of Caenorhabditis elegans. Curr Biol 9(9):493–496PubMedCrossRefGoogle Scholar
  18. Brisbin S, Liu J, Boudreau J, Peng J, Evangelista M, Chin-Sang I (2009) A role for C. elegans Eph RTK signaling in PTEN regulation. Dev Cell 17(4):459–469. doi: 10.1016/j.devcel.2009.08.009 PubMedCrossRefGoogle Scholar
  19. Brock TJ, Browse J, Watts JL (2006) Genetic regulation of unsaturated fatty acid composition in C. elegans. PLoS Genet 2(7), e108. doi: 10.1371/journal.pgen.0020108 PubMedCentralPubMedCrossRefGoogle Scholar
  20. Budovskaya YV, Wu K, Southworth LK, Jiang M, Tedesco P, Johnson TE, Kim SK (2008) An elt-3/elt-5/elt-6 GATA transcription circuit guides aging in C. elegans. Cell 134(2):291–303. doi: 10.1016/j.cell.2008.05.044 PubMedCrossRefGoogle Scholar
  21. Burnett C, Valentini S, Cabreiro F, Goss M, Somogyvari M, Piper MD, Hoddinott M, Sutphin GL, Leko V, McElwee JJ, Vazquez-Manrique RP, Orfila AM, Ackerman D, Au C, Vinti G, Riesen M, Howard K, Neri C, Bedalov A, Kaeberlein M, Soti C, Partridge L, Gems D (2011) Absence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila. Nature 477(7365):482–485. doi: 10.1038/nature10296 PubMedCentralPubMedCrossRefGoogle Scholar
  22. Cabreiro F, Ackerman D, Doonan R, Araiz C, Back P, Papp D, Braeckman BP, Gems D (2011) Increased life span from overexpression of superoxide dismutase in Caenorhabditis elegans is not caused by decreased oxidative damage. Free Radic Biol Med 51(8):1575–1582. doi: 10.1016/j.freeradbiomed.2011.07.020 PubMedCentralPubMedCrossRefGoogle Scholar
  23. Cargill SL, Carey JR, Muller HG, Anderson G (2003) Age of ovary determines remaining life expectancy in old ovariectomized mice. Aging Cell 2(3):185–190PubMedCentralPubMedCrossRefGoogle Scholar
  24. Carrano AC, Liu Z, Dillin A, Hunter T (2009) A conserved ubiquitination pathway determines longevity in response to diet restriction. Nature 460(7253):396–399. doi: 10.1038/nature08130 PubMedCentralPubMedGoogle Scholar
  25. Carrano AC, Dillin A, Hunter T (2014) A Kruppel-like factor downstream of the E3 ligase WWP-1 mediates dietary-restriction-induced longevity in Caenorhabditis elegans. Nat Commun 5:3772. doi: 10.1038/ncomms4772 PubMedCentralPubMedCrossRefGoogle Scholar
  26. Chamoli M, Singh A, Malik Y, Mukhopadhyay A (2014) A novel kinase regulates dietary restriction-mediated longevity in Caenorhabditis elegans. Aging Cell 13(4):641–655. doi: 10.1111/acel.12218 PubMedCentralPubMedCrossRefGoogle Scholar
  27. Chen D, Thomas EL, Kapahi P (2009) HIF-1 modulates dietary restriction-mediated lifespan extension via IRE-1 in Caenorhabditis elegans. PLoS Genet 5(5), e1000486. doi: 10.1371/journal.pgen.1000486 PubMedCentralPubMedCrossRefGoogle Scholar
  28. Chen AT, Guo C, Dumas KJ, Ashrafi K, Hu PJ (2013a) Effects of Caenorhabditis elegans sgk-1 mutations on lifespan, stress resistance, and DAF-16/FoxO regulation. Aging Cell 12(5):932–940. doi: 10.1111/acel.12120 PubMedCentralPubMedCrossRefGoogle Scholar
  29. Chen D, Li PW, Goldstein BA, Cai W, Thomas EL, Chen F, Hubbard AE, Melov S, Kapahi P (2013b) Germline signaling mediates the synergistically prolonged longevity produced by double mutations in daf-2 and rsks-1 in C. elegans. Cell Rep 5(6):1600–1610. doi: 10.1016/j.celrep.2013.11.018 PubMedCentralPubMedCrossRefGoogle Scholar
  30. Chiang WC, Ching TT, Lee HC, Mousigian C, Hsu AL (2012) HSF-1 regulators DDL-1/2 link insulin-like signaling to heat-shock responses and modulation of longevity. Cell 148(1–2):322–334. doi: 10.1016/j.cell.2011.12.019 PubMedCentralPubMedCrossRefGoogle Scholar
  31. Ching TT, Paal AB, Mehta A, Zhong L, Hsu AL (2010) drr-2 encodes an eIF4H that acts downstream of TOR in diet-restriction-induced longevity of C. elegans. Aging Cell 9(4):545–557. doi: 10.1111/j.1474-9726.2010.00580.x PubMedCentralPubMedCrossRefGoogle Scholar
  32. Cristina D, Cary M, Lunceford A, Clarke C, Kenyon C (2009) A regulated response to impaired respiration slows behavioral rates and increases lifespan in Caenorhabditis elegans. PLoS Genet 5(4), e1000450. doi: 10.1371/journal.pgen.1000450 PubMedCentralPubMedCrossRefGoogle Scholar
  33. Curran SP, Ruvkun G (2007) Lifespan regulation by evolutionarily conserved genes essential for viability. PLoS Genet 3(4), e56. doi: 10.1371/journal.pgen.0030056 PubMedCentralPubMedCrossRefGoogle Scholar
  34. Curran SP, Wu X, Riedel CG, Ruvkun G (2009) A soma-to-germline transformation in long-lived Caenorhabditis elegans mutants. Nature 459(7250):1079–1084. doi: 10.1038/nature08106 PubMedCentralPubMedCrossRefGoogle Scholar
  35. Curtis R, O'Connor G, DiStefano PS (2006) Aging networks in Caenorhabditis elegans: AMP-activated protein kinase (aak-2) links multiple aging and metabolism pathways. Aging Cell 5(2):119–126. doi: 10.1111/j.1474-9726.2006.00205.x PubMedCrossRefGoogle Scholar
  36. de Jong L, Meng Y, Dent J, Hekimi S (2004) Thiamine pyrophosphate biosynthesis and transport in the nematode Caenorhabditis elegans. Genetics 168(2):845–854. doi: 10.1534/genetics.104.028605 PubMedCentralPubMedCrossRefGoogle Scholar
  37. de Lencastre A, Pincus Z, Zhou K, Kato M, Lee SS, Slack FJ (2010) MicroRNAs both promote and antagonize longevity in C. elegans. Curr Biol 20(24):2159–2168. doi: 10.1016/j.cub.2010.11.015 PubMedCentralPubMedCrossRefGoogle Scholar
  38. Dillin A, Crawford DK, Kenyon C (2002a) Timing requirements for insulin/IGF-1 signaling in C. elegans. Science 298(5594):830–834. doi: 10.1126/science.1074240 PubMedCrossRefGoogle Scholar
  39. Dillin A, Hsu AL, Arantes-Oliveira N, Lehrer-Graiwer J, Hsin H, Fraser AG, Kamath RS, Ahringer J, Kenyon C (2002b) Rates of behavior and aging specified by mitochondrial function during development. Science 298(5602):2398–2401. doi: 10.1126/science.1077780 PubMedCrossRefGoogle Scholar
  40. Dorman JB, Albinder B, Shroyer T, Kenyon C (1995) The age-1 and daf-2 genes function in a common pathway to control the lifespan of Caenorhabditis elegans. Genetics 141(4):1399–1406PubMedCentralPubMedGoogle Scholar
  41. Durieux J, Wolff S, Dillin A (2011) The cell-non-autonomous nature of electron transport chain-mediated longevity. Cell 144(1):79–91. doi: 10.1016/j.cell.2010.12.016 PubMedCentralPubMedCrossRefGoogle Scholar
  42. Egan DF, Shackelford DB, Mihaylova MM, Gelino S, Kohnz RA, Mair W, Vasquez DS, Joshi A, Gwinn DM, Taylor R, Asara JM, Fitzpatrick J, Dillin A, Viollet B, Kundu M, Hansen M, Shaw RJ (2011) Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Science 331(6016):456–461. doi: 10.1126/science.1196371 PubMedCentralPubMedCrossRefGoogle Scholar
  43. Essers MA, de Vries-Smits LM, Barker N, Polderman PE, Burgering BM, Korswagen HC (2005) Functional interaction between beta-catenin and FOXO in oxidative stress signaling. Science 308(5725):1181–1184. doi: 10.1126/science.1109083 PubMedCrossRefGoogle Scholar
  44. Essers Paul B, Nonnekens J, Goos Yvonne J, Betist Marco C, Viester Marjon D, Mossink B, Lansu N, Korswagen Hendrik C, Jelier R, Brenkman Arjan B, MacInnes Alyson W (2015) A long noncoding RNA on the ribosome is required for lifespan extension. Cell Rep 10(3):339–345. doi: 10.1016/j.celrep.2014.12.029 CrossRefGoogle Scholar
  45. Evans DS, Kapahi P, Hsueh WC, Kockel L (2011) TOR signaling never gets old: aging, longevity and TORC1 activity. Ageing Res Rev 10(2):225–237. doi: 10.1016/j.arr.2010.04.001 PubMedCentralPubMedCrossRefGoogle Scholar
  46. Ewald CY, Landis JN, Abate JP, Murphy CT, Blackwell TK (2014) Dauer-independent insulin/IGF-1-signalling implicates collagen remodelling in longevity. Nature. doi: 10.1038/nature14021 PubMedCentralGoogle Scholar
  47. Ewbank JJ, Barnes TM, Lakowski B, Lussier M, Bussey H, Hekimi S (1997) Structural and functional conservation of the Caenorhabditis elegans timing gene clk-1. Science 275(5302):980–983PubMedCrossRefGoogle Scholar
  48. Feng J, Bussiere F, Hekimi S (2001) Mitochondrial electron transport is a key determinant of life span in Caenorhabditis elegans. Dev Cell 1(5):633–644PubMedCrossRefGoogle Scholar
  49. Fernandes de Abreu DA, Caballero A, Fardel P, Stroustrup N, Chen Z, Lee K, Keyes WD, Nash ZM, Lopez-Moyado IF, Vaggi F, Cornils A, Regenass M, Neagu A, Ostojic I, Liu C, Cho Y, Sifoglu D, Shen Y, Fontana W, Lu H, Csikasz-Nagy A, Murphy CT, Antebi A, Blanc E, Apfeld J, Zhang Y, Alcedo J, Ch'ng Q (2014) An insulin-to-insulin regulatory network orchestrates phenotypic specificity in development and physiology. PLoS Genet 10(3), e1004225. doi: 10.1371/journal.pgen.1004225 PubMedCentralPubMedCrossRefGoogle Scholar
  50. Fisher AL, Lithgow GJ (2006) The nuclear hormone receptor DAF-12 has opposing effects on Caenorhabditis elegans lifespan and regulates genes repressed in multiple long-lived worms. Aging Cell 5(2):127–138. doi: 10.1111/j.1474-9726.2006.00203.x PubMedCrossRefGoogle Scholar
  51. Flatt T, Min KJ, D'Alterio C, Villa-Cuesta E, Cumbers J, Lehmann R, Jones DL, Tatar M (2008) Drosophila germ-line modulation of insulin signaling and lifespan. Proc Natl Acad Sci U S A 105(17):6368–6373. doi: 10.1073/pnas.0709128105 PubMedCentralPubMedCrossRefGoogle Scholar
  52. Friedman DB, Johnson TE (1988) Three mutants that extend both mean and maximum life span of the nematode, Caenorhabditis elegans, define the age-1 gene. J Gerontol 43(4):B102–B109PubMedCrossRefGoogle Scholar
  53. Gaglia MM, Jeong DE, Ryu EA, Lee D, Kenyon C, Lee SJ (2012) Genes that act downstream of sensory neurons to influence longevity, Dauer formation, and pathogen responses in Caenorhabditis elegans. PLoS Genet 8(12), e1003133. doi: 10.1371/journal.pgen.1003133 PubMedCentralPubMedCrossRefGoogle Scholar
  54. Garigan D, Hsu AL, Fraser AG, Kamath RS, Ahringer J, Kenyon C (2002) Genetic analysis of tissue aging in Caenorhabditis elegans: a role for heat-shock factor and bacterial proliferation. Genetics 161(3):1101–1112PubMedCentralPubMedGoogle Scholar
  55. Garsin DA, Villanueva JM, Begun J, Kim DH, Sifri CD, Calderwood SB, Ruvkun G, Ausubel FM (2003) Long-lived C. elegans daf-2 mutants are resistant to bacterial pathogens. Science 300 (5627):1921. doi: 10.1126/science.1080147
  56. Gems D, Sutton AJ, Sundermeyer ML, Albert PS, King KV, Edgley ML, Larsen PL, Riddle DL (1998) Two pleiotropic classes of daf-2 mutation affect larval arrest, adult behavior, reproduction and longevity in Caenorhabditis elegans. Genetics 150(1):129–155PubMedCentralPubMedGoogle Scholar
  57. Gerisch B, Weitzel C, Kober-Eisermann C, Rottiers V, Antebi A (2001) A hormonal signaling pathway influencing C. elegans metabolism, reproductive development, and life span. Dev Cell 1(6):841–851PubMedCrossRefGoogle Scholar
  58. Gerisch B, Rottiers V, Li D, Motola DL, Cummins CL, Lehrach H, Mangelsdorf DJ, Antebi A (2007) A bile acid-like steroid modulates Caenorhabditis elegans lifespan through nuclear receptor signaling. Proc Natl Acad Sci U S A 104(12):5014–5019. doi: 10.1073/pnas.0700847104 PubMedCentralPubMedCrossRefGoogle Scholar
  59. Gharbi H, Fabretti F, Bharill P, Rinschen MM, Brinkkotter S, Frommolt P, Burst V, Schermer B, Benzing T, Muller RU (2013) Loss of the Birt-Hogg-Dube gene product folliculin induces longevity in a hypoxia-inducible factor-dependent manner. Aging Cell 12(4):593–603. doi: 10.1111/acel.12081 PubMedCrossRefGoogle Scholar
  60. Ghazi A, Henis-Korenblit S, Kenyon C (2007) Regulation of Caenorhabditis elegans lifespan by a proteasomal E3 ligase complex. Proc Natl Acad Sci U S A 104(14):5947–5952. doi: 10.1073/pnas.0700638104 PubMedCentralPubMedCrossRefGoogle Scholar
  61. Ghazi A, Henis-Korenblit S, Kenyon C (2009) A transcription elongation factor that links signals from the reproductive system to lifespan extension in Caenorhabditis elegans. PLoS Genet 5(9), e1000639. doi: 10.1371/journal.pgen.1000639 PubMedCentralPubMedCrossRefGoogle Scholar
  62. Goudeau J, Bellemin S, Toselli-Mollereau E, Shamalnasab M, Chen Y, Aguilaniu H (2011) Fatty acid desaturation links germ cell loss to longevity through NHR-80/HNF4 in C. elegans. PLoS Biol 9(3), e1000599. doi: 10.1371/journal.pbio.1000599 PubMedCentralPubMedCrossRefGoogle Scholar
  63. Green DR, Galluzzi L, Kroemer G (2014) Metabolic control of cell death. Science 345(6203):1250256PubMedCentralPubMedCrossRefGoogle Scholar
  64. Greer EL, Brunet A (2009) Different dietary restriction regimens extend lifespan by both independent and overlapping genetic pathways in C. elegans. Aging Cell 8(2):113–127. doi: 10.1111/j.1474-9726.2009.00459.x PubMedCentralPubMedCrossRefGoogle Scholar
  65. Greer EL, Dowlatshahi D, Banko MR, Villen J, Hoang K, Blanchard D, Gygi SP, Brunet A (2007) An AMPK-FOXO pathway mediates longevity induced by a novel method of dietary restriction in C. elegans. Curr Biol 17(19):1646–1656. doi: 10.1016/j.cub.2007.08.047 PubMedCentralPubMedCrossRefGoogle Scholar
  66. Hahm JH, Kim S, Paik YK (2009) Endogenous cGMP regulates adult longevity via the insulin signaling pathway in Caenorhabditis elegans. Aging Cell 8(4):473–483. doi: 10.1111/j.1474-9726.2009.00495.x PubMedCrossRefGoogle Scholar
  67. Hamilton B, Dong Y, Shindo M, Liu W, Odell I, Ruvkun G, Lee SS (2005) A systematic RNAi screen for longevity genes in C. elegans. Genes Dev 19(13):1544–1555. doi: 10.1101/gad.1308205 PubMedCentralPubMedCrossRefGoogle Scholar
  68. Hansen M, Hsu AL, Dillin A, Kenyon C (2005) New genes tied to endocrine, metabolic, and dietary regulation of lifespan from a Caenorhabditis elegans genomic RNAi screen. PLoS Genet 1(1):119–128. doi: 10.1371/journal.pgen.0010017 PubMedCrossRefGoogle Scholar
  69. Hansen M, Taubert S, Crawford D, Libina N, Lee SJ, Kenyon C (2007) Lifespan extension by conditions that inhibit translation in Caenorhabditis elegans. Aging Cell 6(1):95–110. doi: 10.1111/j.1474-9726.2006.00267.x PubMedCrossRefGoogle Scholar
  70. Hansen M, Chandra A, Mitic LL, Onken B, Driscoll M, Kenyon C (2008) A role for autophagy in the extension of lifespan by dietary restriction in C. elegans. PLoS Genet 4(2), e24. doi: 10.1371/journal.pgen.0040024 PubMedCentralPubMedCrossRefGoogle Scholar
  71. Hardie DG (2014) AMPK-sensing energy while talking to other signaling pathways. Cell Metab 20(6):939–952. doi: 10.1016/j.cmet.2014.09.013 PubMedCrossRefGoogle Scholar
  72. Harman D (1956) Aging: a theory based on free radical and radiation chemistry. J Gerontol 11(3):298–300PubMedCrossRefGoogle Scholar
  73. Harman D (1972) The biologic clock: the mitochondria? J Am Geriatr Soc 20(4):145–147PubMedCrossRefGoogle Scholar
  74. Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle CM, Flurkey K, Nadon NL, Wilkinson JE, Frenkel K, Carter CS, Pahor M, Javors MA, Fernandez E, Miller RA (2009) Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 460(7253):392–395. doi: 10.1038/nature08221 PubMedCentralPubMedGoogle Scholar
  75. Hars ES, Qi H, Ryazanov AG, Jin S, Cai L, Hu C, Liu LF (2007) Autophagy regulates ageing in C. elegans. Autophagy 3(2):93–95PubMedCrossRefGoogle Scholar
  76. Hashimoto Y, Ookuma S, Nishida E (2009) Lifespan extension by suppression of autophagy genes in Caenorhabditis elegans. Genes Cells 14(6):717–726. doi: 10.1111/j.1365-2443.2009.01306.x PubMedCrossRefGoogle Scholar
  77. Haynes CM, Fiorese CJ, Lin YF (2013) Evaluating and responding to mitochondrial dysfunction: the mitochondrial unfolded-protein response and beyond. Trends Cell Biol 23(7):311–318. doi: 10.1016/j.tcb.2013.02.002 PubMedCentralPubMedCrossRefGoogle Scholar
  78. Heestand BN, Shen Y, Liu W, Magner DB, Storm N, Meharg C, Habermann B, Antebi A (2013) Dietary restriction induced longevity is mediated by nuclear receptor NHR-62 in Caenorhabditis elegans. PLoS Genet 9(7), e1003651. doi: 10.1371/journal.pgen.1003651 PubMedCentralPubMedCrossRefGoogle Scholar
  79. Henderson ST, Johnson TE (2001) daf-16 integrates developmental and environmental inputs to mediate aging in the nematode Caenorhabditis elegans. Curr Biol 11(24):1975–1980PubMedCrossRefGoogle Scholar
  80. Henis-Korenblit S, Zhang P, Hansen M, McCormick M, Lee SJ, Cary M, Kenyon C (2010) Insulin/IGF-1 signaling mutants reprogram ER stress response regulators to promote longevity. Proc Natl Acad Sci U S A 107(21):9730–9735. doi: 10.1073/pnas.1002575107 PubMedCentralPubMedCrossRefGoogle Scholar
  81. Hertweck M, Gobel C, Baumeister R (2004) C. elegans SGK-1 is the critical component in the Akt/PKB kinase complex to control stress response and life span. Dev Cell 6(4):577–588PubMedCrossRefGoogle Scholar
  82. Honda Y, Honda S (1999) The daf-2 gene network for longevity regulates oxidative stress resistance and Mn-superoxide dismutase gene expression in Caenorhabditis elegans. FASEB J 13(11):1385–1393PubMedGoogle Scholar
  83. Honjoh S, Yamamoto T, Uno M, Nishida E (2009) Signalling through RHEB-1 mediates intermittent fasting-induced longevity in C. elegans. Nature 457(7230):726–730. doi: 10.1038/nature07583 PubMedCrossRefGoogle Scholar
  84. Honnen SJ, Buchter C, Schroder V, Hoffmann M, Kohara Y, Kampkotter A, Bossinger O (2012) C. elegans VANG-1 modulates life span via insulin/IGF-1-like signaling. PLoS One 7(2), e32183. doi: 10.1371/journal.pone.0032183 PubMedCentralPubMedCrossRefGoogle Scholar
  85. Houtkooper RH, Mouchiroud L, Ryu D, Moullan N, Katsyuba E, Knott G, Williams RW, Auwerx J (2013) Mitonuclear protein imbalance as a conserved longevity mechanism. Nature 497(7450):451–457. doi: 10.1038/nature12188 PubMedCrossRefGoogle Scholar
  86. Hsin H, Kenyon C (1999) Signals from the reproductive system regulate the lifespan of C. elegans. Nature 399(6734):362–366. doi: 10.1038/20694 PubMedCrossRefGoogle Scholar
  87. Hsu AL, Murphy CT, Kenyon C (2003) Regulation of aging and age-related disease by DAF-16 and heat-shock factor. Science 300(5622):1142–1145. doi: 10.1126/science.1083701 PubMedCrossRefGoogle Scholar
  88. Huang X, Zhang H, Zhang H (2011) The zinc-finger protein SEA-2 regulates larval developmental timing and adult lifespan in C. elegans. Development 138(10):2059–2068. doi: 10.1242/dev.057109 PubMedCrossRefGoogle Scholar
  89. Hwang AB, Jeong DE, Lee SJ (2012) Mitochondria and organismal longevity. Curr Genomics 13(7):519–532. doi: 10.2174/138920212803251427 PubMedCentralPubMedCrossRefGoogle Scholar
  90. Hwang AB, Ryu EA, Artan M, Chang HW, Kabir MH, Nam HJ, Lee D, Yang JS, Kim S, Mair WB, Lee C, Lee SS, Lee SJ (2014) Feedback regulation via AMPK and HIF-1 mediates ROS-dependent longevity in Caenorhabditis elegans. Proc Natl Acad Sci U S A 111(42):E4458–E4467. doi: 10.1073/pnas.1411199111 PubMedCentralPubMedCrossRefGoogle Scholar
  91. Jeong DE, Artan M, Seo K, Lee SJ (2012) Regulation of lifespan by chemosensory and thermosensory systems: findings in invertebrates and their implications in mammalian aging. Front Genet 3:218. doi: 10.3389/fgene.2012.00218 PubMedCentralPubMedCrossRefGoogle Scholar
  92. Jia K, Albert PS, Riddle DL (2002) DAF-9, a cytochrome P450 regulating C. elegans larval development and adult longevity. Development 129(1):221–231PubMedGoogle Scholar
  93. Jia K, Chen D, Riddle DL (2004) The TOR pathway interacts with the insulin signaling pathway to regulate C. elegans larval development, metabolism and life span. Development 131(16):3897–3906. doi: 10.1242/dev.01255 PubMedCrossRefGoogle Scholar
  94. Jia K, Levine B (2007) Autophagy is required for dietary restriction-mediated life span extension in C. elegans. Autophagy 3(6):597–599PubMedCrossRefGoogle Scholar
  95. Jia K, Thomas C, Akbar M, Sun Q, Adams-Huet B, Gilpin C, Levine B (2009) Autophagy genes protect against Salmonella typhimurium infection and mediate insulin signaling-regulated pathogen resistance. Proc Natl Acad Sci U S A 106(34):14564–14569. doi: 10.1073/pnas.0813319106 PubMedCentralPubMedCrossRefGoogle Scholar
  96. Jin C, Li J, Green CD, Yu X, Tang X, Han D, Xian B, Wang D, Huang X, Cao X, Yan Z, Hou L, Liu J, Shukeir N, Khaitovich P, Chen CD, Zhang H, Jenuwein T, Han JD (2011) Histone demethylase UTX-1 regulates C. elegans life span by targeting the insulin/IGF-1 signaling pathway. Cell Metab 14(2):161–172. doi: 10.1016/j.cmet.2011.07.001 PubMedCrossRefGoogle Scholar
  97. Johnson SC, Rabinovitch PS, Kaeberlein M (2013) mTOR is a key modulator of ageing and age-related disease. Nature 493(7432):338–345. doi: 10.1038/nature11861 PubMedCentralPubMedCrossRefGoogle Scholar
  98. Johnson DW, Llop JR, Farrell SF, Yuan J, Stolzenburg LR, Samuelson AV (2014) The Caenorhabditis elegans Myc-Mondo/Mad complexes integrate diverse longevity signals. PLoS Genet 10(4), e1004278. doi: 10.1371/journal.pgen.1004278 PubMedCentralPubMedCrossRefGoogle Scholar
  99. Kaletsky R, Murphy CT (2010) The role of insulin/IGF-like signaling in C. elegans longevity and aging. Dis Model Mech 3(7–8):415–419. doi: 10.1242/dmm.001040 PubMedCrossRefGoogle Scholar
  100. Kapahi P, Chen D, Rogers AN, Katewa SD, Li PW, Thomas EL, Kockel L (2010) With TOR, less is more: a key role for the conserved nutrient-sensing TOR pathway in aging. Cell Metab 11(6):453–465. doi: 10.1016/j.cmet.2010.05.001 PubMedCentralPubMedCrossRefGoogle Scholar
  101. Kawano T, Ito Y, Ishiguro M, Takuwa K, Nakajima T, Kimura Y (2000) Molecular cloning and characterization of a new insulin/IGF-like peptide of the nematode Caenorhabditis elegans. Biochem Biophys Res Commun 273(2):431–436. doi: 10.1006/bbrc.2000.2971 PubMedCrossRefGoogle Scholar
  102. Kenyon C, Chang J, Gensch E, Rudner A, Tabtiang R (1993) A C. elegans mutant that lives twice as long as wild type. Nature 366(6454):461–464. doi: 10.1038/366461a0 PubMedCrossRefGoogle Scholar
  103. Kenyon CJ (2010) The genetics of ageing. Nature 464(7288):504–512. doi: 10.1038/nature08980 PubMedCrossRefGoogle Scholar
  104. Khan MH, Ligon M, Hussey LR, Hufnal B, Farber R 2nd, Munkacsy E, Rodriguez A, Dillow A, Kahlig E, Rea SL (2013) TAF-4 is required for the life extension of isp-1, clk-1 and tpk-1 Mit mutants. Aging 5(10):741–758PubMedCentralPubMedGoogle Scholar
  105. Kim SK, Budovskaya YV, Johnson TE (2013) Reconciliation of daf-2 suppression by elt-3 in Caenorhabditis elegans from Tonsaker et al. (2012) and Kim et al. (2012). Mech Ageing Dev 134(1–2):64–65. doi: 10.1016/j.mad.2012.12.004 PubMedCrossRefGoogle Scholar
  106. Kim Y, Sun H (2007) Functional genomic approach to identify novel genes involved in the regulation of oxidative stress resistance and animal lifespan. Aging Cell 6(4):489–503. doi: 10.1111/j.1474-9726.2007.00302.x PubMedCrossRefGoogle Scholar
  107. Lamitina ST, Strange K (2005) Transcriptional targets of DAF-16 insulin signaling pathway protect C. elegans from extreme hypertonic stress. Am J Physiol Cell Physiol 288(2):C467–C474. doi: 10.1152/ajpcell.00451.2004 PubMedCrossRefGoogle Scholar
  108. Lanjuin A, Sengupta P (2002) Regulation of chemosensory receptor expression and sensory signaling by the KIN-29 Ser/Thr kinase. Neuron 33(3):369–381PubMedCrossRefGoogle Scholar
  109. Lans H, Jansen G (2007) Multiple sensory G proteins in the olfactory, gustatory and nociceptive neurons modulate longevity in Caenorhabditis elegans. Dev Biol 303(2):474–482. doi: 10.1016/j.ydbio.2006.11.028 PubMedCrossRefGoogle Scholar
  110. Lapierre LR, Gelino S, Melendez A, Hansen M (2011) Autophagy and lipid metabolism coordinately modulate life span in germline-less C. elegans. Curr Biol 21(18):1507–1514. doi: 10.1016/j.cub.2011.07.042 PubMedCentralPubMedCrossRefGoogle Scholar
  111. Lapierre LR, De Magalhaes Filho CD, McQuary PR, Chu CC, Visvikis O, Chang JT, Gelino S, Ong B, Davis AE, Irazoqui JE, Dillin A, Hansen M (2013a) The TFEB orthologue HLH-30 regulates autophagy and modulates longevity in Caenorhabditis elegans. Nat Commun 4:2267. doi: 10.1038/ncomms3267 PubMedGoogle Scholar
  112. Lapierre LR, Silvestrini MJ, Nunez L, Ames K, Wong S, Le TT, Hansen M, Melendez A (2013b) Autophagy genes are required for normal lipid levels in C. elegans. Autophagy 9(3):278–286. doi: 10.4161/auto.22930 PubMedCentralPubMedCrossRefGoogle Scholar
  113. Laplante M, Sabatini DM (2012) mTOR signaling in growth control and disease. Cell 149(2):274–293. doi: 10.1016/j.cell.2012.03.017 PubMedCentralPubMedCrossRefGoogle Scholar
  114. Larsen PL, Albert PS, Riddle DL (1995) Genes that regulate both development and longevity in Caenorhabditis elegans. Genetics 139(4):1567–1583PubMedCentralPubMedGoogle Scholar
  115. Lakowski B, Hekimi S (1998) The genetics of caloric restriction in Caenorhabditis elegans. Proc Natl Acad Sci 95(22):13091–13096PubMedCentralPubMedCrossRefGoogle Scholar
  116. Lee BH, Ashrafi K (2008) A TRPV channel modulates C. elegans neurosecretion, larval starvation survival, and adult lifespan. PLoS Genet 4(10), e1000213. doi: 10.1371/journal.pgen.1000213 PubMedCentralPubMedCrossRefGoogle Scholar
  117. Lee SJ, Kenyon C (2009) Regulation of the longevity response to temperature by thermosensory neurons in Caenorhabditis elegans. Curr Biol 19(9):715–722. doi: 10.1016/j.cub.2009.03.041 PubMedCentralPubMedCrossRefGoogle Scholar
  118. Lee RY, Hench J, Ruvkun G (2001) Regulation of C. elegans DAF-16 and its human ortholog FKHRL1 by the daf-2 insulin-like signaling pathway. Curr Biol 11(24):1950–1957PubMedCrossRefGoogle Scholar
  119. Lee SS, Lee RY, Fraser AG, Kamath RS, Ahringer J, Ruvkun G (2003) A systematic RNAi screen identifies a critical role for mitochondria in C. elegans longevity. Nat Genet 33(1):40–48. doi: 10.1038/ng1056 PubMedCrossRefGoogle Scholar
  120. Lee SJ, Murphy CT, Kenyon C (2009) Glucose shortens the life span of C. elegans by downregulating DAF-16/FOXO activity and aquaporin gene expression. Cell Metab 10(5):379–391. doi: 10.1016/j.cmet.2009.10.003 PubMedCentralPubMedCrossRefGoogle Scholar
  121. Lee SJ, Hwang AB, Kenyon C (2010) Inhibition of respiration extends C. elegans life span via reactive oxygen species that increase HIF-1 activity. Curr Biol 20(23):2131–2136. doi: 10.1016/j.cub.2010.10.057 PubMedCentralPubMedCrossRefGoogle Scholar
  122. Lehtinen MK, Yuan Z, Boag PR, Yang Y, Villen J, Becker EB, DiBacco S, de la Iglesia N, Gygi S, Blackwell TK, Bonni A (2006) A conserved MST-FOXO signaling pathway mediates oxidative-stress responses and extends life span. Cell 125(5):987–1001. doi: 10.1016/j.cell.2006.03.046 PubMedCrossRefGoogle Scholar
  123. Leiser SF, Begun A, Kaeberlein M (2011) HIF-1 modulates longevity and healthspan in a temperature-dependent manner. Aging Cell 10(2):318–326. doi: 10.1111/j.1474-9726.2011.00672.x PubMedCentralPubMedCrossRefGoogle Scholar
  124. Levine B, Klionsky DJ (2004) Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev Cell 6(4):463–477PubMedCrossRefGoogle Scholar
  125. Li J, Tewari M, Vidal M, Lee SS (2007a) The 14-3-3 protein FTT-2 regulates DAF-16 in Caenorhabditis elegans. Dev Biol 301(1):82–91PubMedCentralPubMedCrossRefGoogle Scholar
  126. Li W, Gao B, Lee SM, Bennett K, Fang D (2007b) RLE-1, an E3 ubiquitin ligase, regulates C. elegans aging by catalyzing DAF-16 polyubiquitination. Dev Cell 12(2):235–246. doi: 10.1016/j.devcel.2006.12.002 PubMedCrossRefGoogle Scholar
  127. Li J, Ebata A, Dong Y, Rizki G, Iwata T, Lee SS (2008) Caenorhabditis elegans HCF-1 functions in longevity maintenance as a DAF-16 regulator. PLoS Biol 6(9), e233. doi: 10.1371/journal.pbio.0060233 PubMedCentralPubMedCrossRefGoogle Scholar
  128. Libert S, Zwiener J, Chu X, Vanvoorhies W, Roman G, Pletcher SD (2007) Regulation of Drosophila life span by olfaction and food-derived odors. Science 315(5815):1133–1137. doi: 10.1126/science.1136610 PubMedCrossRefGoogle Scholar
  129. Lin K, Dorman JB, Rodan A, Kenyon C (1997) daf-16: An HNF-3/forkhead family member that can function to double the life-span of Caenorhabditis elegans. Science 278(5341):1319–1322PubMedCrossRefGoogle Scholar
  130. Lin K, Hsin H, Libina N, Kenyon C (2001) Regulation of the Caenorhabditis elegans longevity protein DAF-16 by insulin/IGF-1 and germline signaling. Nat Genet 28(2):139–145. doi: 10.1038/88850 PubMedCrossRefGoogle Scholar
  131. Linford NJ, Kuo TH, Chan TP, Pletcher SD (2011) Sensory perception and aging in model systems: from the outside in. Annu Rev Cell Dev Biol 27:759–785. doi: 10.1146/annurev-cellbio-092910-154240 PubMedCentralPubMedCrossRefGoogle Scholar
  132. Lithgow GJ, White TM, Melov S, Johnson TE (1995) Thermotolerance and extended life-span conferred by single-gene mutations and induced by thermal stress. Proc Natl Acad Sci U S A 92(16):7540–7544PubMedCentralPubMedCrossRefGoogle Scholar
  133. Lithgow GJ, Kapahi P (2011) Life span extension via eIF4G inhibition is mediated by posttranscriptional remodeling of stress response gene expression in C. elegans. Cell Metab 14(1):55–66. doi: 10.1016/j.cmet.2011.05.010 PubMedCentralPubMedCrossRefGoogle Scholar
  134. Lucanic M, Held JM, Vantipalli MC, Klang IM, Graham JB, Gibson BW, Lithgow GJ, Gill MS (2011) N-acylethanolamine signalling mediates the effect of diet on lifespan in Caenorhabditis elegans. Nature 473(7346):226–229. doi: 10.1038/nature10007 PubMedCentralPubMedCrossRefGoogle Scholar
  135. Magner DB, Wollam J, Shen Y, Hoppe C, Li D, Latza C, Rottiers V, Hutter H, Antebi A (2013) The NHR-8 nuclear receptor regulates cholesterol and bile acid homeostasis in C. elegans. Cell Metab 18(2):212–224. doi: 10.1016/j.cmet.2013.07.007 PubMedCentralPubMedCrossRefGoogle Scholar
  136. Mahanti P, Bose N, Bethke A, Judkins JC, Wollam J, Dumas KJ, Zimmerman AM, Campbell SL, Hu PJ, Antebi A, Schroeder FC (2014) Comparative metabolomics reveals endogenous ligands of DAF-12, a nuclear hormone receptor, regulating C. elegans development and lifespan. Cell Metab 19(1):73–83. doi: 10.1016/j.cmet.2013.11.024 PubMedCentralPubMedCrossRefGoogle Scholar
  137. Maier W, Adilov B, Regenass M, Alcedo J (2010) A neuromedin U receptor acts with the sensory system to modulate food type-dependent effects on C. elegans lifespan. PLoS Biol 8(5), e1000376. doi: 10.1371/journal.pbio.1000376 PubMedCentralPubMedCrossRefGoogle Scholar
  138. Malone EA, Inoue T, Thomas JH (1996) Genetic analysis of the roles of daf-28 and age-1 in regulating Caenorhabditis elegans Dauer formation. Genetics 143(3):1193–1205PubMedCentralPubMedGoogle Scholar
  139. Masse I, Molin L, Billaud M, Solari F (2005) Lifespan and Dauer regulation by tissue-specific activities of Caenorhabditis elegans DAF-18. Dev Biol 286(1):91–101. doi: 10.1016/j.ydbio.2005.07.010 PubMedCrossRefGoogle Scholar
  140. Matsunaga Y, Gengyo-Ando K, Mitani S, Iwasaki T, Kawano T (2012) Physiological function, expression pattern, and transcriptional regulation of a Caenorhabditis elegans insulin-like peptide, INS-18. Biochem Biophys Res Commun 423(3):478–483. doi: 10.1016/j.bbrc.2012.05.145 PubMedCrossRefGoogle Scholar
  141. Maures TJ, Greer EL, Hauswirth AG, Brunet A (2011) The H3K27 demethylase UTX-1 regulates C. elegans lifespan in a germline-independent, insulin-dependent manner. Aging Cell 10(6):980–990. doi: 10.1111/j.1474-9726.2011.00738.x PubMedCentralPubMedCrossRefGoogle Scholar
  142. McCormick M, Chen K, Ramaswamy P, Kenyon C (2012) New genes that extend Caenorhabditis elegans' lifespan in response to reproductive signals. Aging Cell 11(2):192–202. doi: 10.1111/j.1474-9726.2011.00768.x PubMedCentralPubMedCrossRefGoogle Scholar
  143. Mehta R, Steinkraus KA, Sutphin GL, Ramos FJ, Shamieh LS, Huh A, Davis C, Chandler-Brown D, Kaeberlein M (2009) Proteasomal regulation of the hypoxic response modulates aging in C. elegans. Science 324(5931):1196–1198. doi: 10.1126/science.1173507 PubMedCentralPubMedCrossRefGoogle Scholar
  144. Melendez A, Talloczy Z, Seaman M, Eskelinen EL, Hall DH, Levine B (2003) Autophagy genes are essential for Dauer development and life-span extension in C. elegans. Science 301(5638):1387–1391. doi: 10.1126/science.1087782 PubMedCrossRefGoogle Scholar
  145. Mihaylova VT, Borland CZ, Manjarrez L, Stern MJ, 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 U S A 96(13):7427–7432PubMedCentralPubMedCrossRefGoogle Scholar
  146. Morley JF, Morimoto RI (2004) Regulation of longevity in Caenorhabditis elegans by heat shock factor and molecular chaperones. Mol Biol Cell 15(2):657–664. doi: 10.1091/mbc.E03-07-0532 PubMedCentralPubMedCrossRefGoogle Scholar
  147. Morley JF, Brignull HR, Weyers JJ, Morimoto RI (2002) The threshold for polyglutamine-expansion protein aggregation and cellular toxicity is dynamic and influenced by aging in Caenorhabditis elegans. Proc Natl Acad Sci U S A 99(16):10417–10422. doi: 10.1073/pnas.152161099 PubMedCentralPubMedCrossRefGoogle Scholar
  148. Moroz N, Carmona JJ, Anderson E, Hart AC, Sinclair DA, Blackwell TK (2014) Dietary restriction involves NAD(+) -dependent mechanisms and a shift toward oxidative metabolism. Aging Cell 13(6):1075–1085. doi: 10.1111/acel.12273 PubMedCentralPubMedCrossRefGoogle Scholar
  149. Morris JZ, Tissenbaum HA, Ruvkun G (1996) A phosphatidylinositol-3-OH kinase family member regulating longevity and diapause in Caenorhabditis elegans. Nature 382(6591):536–539. doi: 10.1038/382536a0 PubMedCrossRefGoogle Scholar
  150. Motola DL, Cummins CL, Rottiers V, Sharma KK, Li T, Li Y, Suino-Powell K, Xu HE, Auchus RJ, Antebi A, Mangelsdorf DJ (2006) Identification of ligands for DAF-12 that govern Dauer formation and reproduction in C. elegans. Cell 124(6):1209–1223. doi:http://dx.doi.org/10.1016/j.cell.2006.01.037
  151. Mouchiroud L, Houtkooper RH, Moullan N, Katsyuba E, Ryu D, Canto C, Mottis A, Jo YS, Viswanathan M, Schoonjans K, Guarente L, Auwerx J (2013) The NAD(+)/Sirtuin pathway modulates longevity through activation of mitochondrial UPR and FOXO signaling. Cell 154(2):430–441. doi: 10.1016/j.cell.2013.06.016 PubMedCentralPubMedCrossRefGoogle Scholar
  152. Mukhopadhyay A, Deplancke B, Walhout AJ, Tissenbaum HA (2005) C. elegans tubby regulates life span and fat storage by two independent mechanisms. Cell Metab 2(1):35–42. doi: 10.1016/j.cmet.2005.06.004 PubMedCrossRefGoogle Scholar
  153. Muller RU, Fabretti F, Zank S, Burst V, Benzing T, Schermer B (2009) The von Hippel Lindau tumor suppressor limits longevity. J Am Soc Nephrol 20(12):2513–2517. doi: 10.1681/asn.2009050497 PubMedCentralPubMedCrossRefGoogle Scholar
  154. Murphy CT, Hu PJ (2013) Insulin/insulin-like growth factor signaling in C. elegans. WormBook:1–43. doi: 10.1895/wormbook.1.164.1
  155. Murphy CT, Lee SJ, Kenyon C (2007) Tissue entrainment by feedback regulation of insulin gene expression in the endoderm of Caenorhabditis elegans. Proc Natl Acad Sci U S A 104(48):19046–19050. doi: 10.1073/pnas.0709613104 PubMedCentralPubMedCrossRefGoogle Scholar
  156. Murphy CT, McCarroll SA, Bargmann CI, Fraser A, Kamath RS, Ahringer J, Li H, Kenyon C (2003) Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans. Nature 424(6946):277–283. doi: 10.1038/nature01789 PubMedCrossRefGoogle Scholar
  157. Nanji M, Hopper NA, Gems D (2005) LET-60 RAS modulates effects of insulin/IGF-1 signaling on development and aging in Caenorhabditis elegans. Aging Cell 4(5):235–245. doi: 10.1111/j.1474-9726.2005.00166.x PubMedCrossRefGoogle Scholar
  158. Neumann-Haefelin E, Qi W, Finkbeiner E, Walz G, Baumeister R, Hertweck M (2008) SHC-1/p52Shc targets the insulin/IGF-1 and JNK signaling pathways to modulate life span and stress response in C. elegans. Genes Dev 22(19):2721–2735. doi: 10.1101/gad.478408 PubMedCentralPubMedCrossRefGoogle Scholar
  159. Ogg S, Paradis S, Gottlieb S, Patterson GI, Lee L, Tissenbaum HA, Ruvkun G (1997) The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans. Nature 389(6654):994–999. doi: 10.1038/40194 PubMedCrossRefGoogle Scholar
  160. Oh SW, Mukhopadhyay A, Svrzikapa N, Jiang F, Davis RJ, Tissenbaum HA (2005) JNK regulates lifespan in Caenorhabditis elegans by modulating nuclear translocation of forkhead transcription factor/DAF-16. Proc Natl Acad Sci U S A 102(12):4494–4499. doi: 10.1073/pnas.0500749102 PubMedCentralPubMedCrossRefGoogle Scholar
  161. Okuyama T, Inoue H, Ookuma S, Satoh T, Kano K, Honjoh S, Hisamoto N, Matsumoto K, Nishida E (2010) The ERK-MAPK pathway regulates longevity through SKN-1 and insulin-like signaling in Caenorhabditis elegans. J Biol Chem 285(39):30274–30281. doi: 10.1074/jbc.M110.146274 PubMedCentralPubMedCrossRefGoogle Scholar
  162. O'Rourke EJ, Ruvkun G (2013) MXL-3 and HLH-30 transcriptionally link lipolysis and autophagy to nutrient availability. Nat Cell Biol 15(6):668–676. doi: 10.1038/ncb2741 PubMedCentralPubMedCrossRefGoogle Scholar
  163. O'Rourke EJ, Soukas AA, Carr CE, Ruvkun G (2009) C. elegans major fats are stored in vesicles distinct from lysosome-related organelles. Cell Metab 10(5):430–435. doi: 10.1016/j.cmet.2009.10.002 PubMedCentralPubMedCrossRefGoogle Scholar
  164. Padmanabhan S, Mukhopadhyay A, Narasimhan SD, Tesz G, Czech MP, Tissenbaum HA (2009) A PP2A regulatory subunit regulates C. elegans insulin/IGF-1 signaling by modulating AKT-1 phosphorylation. Cell 136(5):939–951. doi: 10.1016/j.cell.2009.01.025 PubMedCentralPubMedCrossRefGoogle Scholar
  165. Paek J, Lo JY, Narasimhan SD, Nguyen TN, Glover-Cutter K, Robida-Stubbs S, Suzuki T, Yamamoto M, Blackwell TK, Curran SP (2012) Mitochondrial SKN-1/Nrf mediates a conserved starvation response. Cell Metab 16(4):526–537. doi: 10.1016/j.cmet.2012.09.007 PubMedCentralPubMedCrossRefGoogle Scholar
  166. Pan KZ, Palter JE, Rogers AN, Olsen A, Chen D, Lithgow GJ, Kapahi P (2007) Inhibition of mRNA translation extends lifespan in Caenorhabditis elegans. Aging Cell 6(1):111–119. doi: 10.1111/j.1474-9726.2006.00266.x PubMedCentralPubMedCrossRefGoogle Scholar
  167. Panowski SH, Wolff S, Aguilaniu H, Durieux J, Dillin A (2007) PHA-4/Foxa mediates diet-restriction-induced longevity of C. elegans. Nature 447(7144):550–555. doi: 10.1038/nature05837 PubMedCrossRefGoogle Scholar
  168. Paradis S, Ailion M, Toker A, Thomas JH, Ruvkun G (1999) A PDK1 homolog is necessary and sufficient to transduce AGE-1 PI3 kinase signals that regulate diapause in Caenorhabditis elegans. Genes Dev 13(11):1438–1452PubMedCentralPubMedCrossRefGoogle Scholar
  169. Paradis S, Ruvkun G (1998) Caenorhabditis elegans Akt/PKB transduces insulin receptor-like signals from AGE-1 PI3 kinase to the DAF-16 transcription factor. Genes Dev 12(16):2488–2498PubMedCentralPubMedCrossRefGoogle Scholar
  170. Park SK, Link CD, Johnson TE (2010) Life-span extension by dietary restriction is mediated by NLP-7 signaling and coelomocyte endocytosis in C. elegans. FASEB J 24(2):383–392. doi: 10.1096/fj.09-142984, fj.09-142984 [pii]PubMedCentralPubMedCrossRefGoogle Scholar
  171. Petrascheck M, Ye X, Buck LB (2007) An antidepressant that extends lifespan in adult Caenorhabditis elegans. Nature 450(7169):553–556PubMedCrossRefGoogle Scholar
  172. Pierce SB, Costa M, Wisotzkey R, Devadhar S, Homburger SA, Buchman AR, Ferguson KC, Heller J, Platt DM, Pasquinelli AA, Liu LX, Doberstein SK, Ruvkun G (2001) Regulation of DAF-2 receptor signaling by human insulin and ins-1, a member of the unusually large and diverse C. elegans insulin gene family. Genes Dev 15(6):672–686. doi: 10.1101/gad.867301 PubMedCentralPubMedCrossRefGoogle Scholar
  173. Piper MD, Partridge L, Raubenheimer D, Simpson SJ (2011) Dietary restriction and aging: a unifying perspective. Cell Metab 14(2):154–160. doi: 10.1016/j.cmet.2011.06.013 PubMedCentralPubMedCrossRefGoogle Scholar
  174. Possik E, Jalali Z, Nouet Y, Yan M, Gingras MC, Schmeisser K, Panaite L, Dupuy F, Kharitidi D, Chotard L, Jones RG, Hall DH, Pause A (2014) Folliculin regulates ampk-dependent autophagy and metabolic stress survival. PLoS Genet 10(4), e1004273. doi: 10.1371/journal.pgen.1004273 PubMedCentralPubMedCrossRefGoogle Scholar
  175. Powell-Coffman JA (2010) Hypoxia signaling and resistance in C. elegans. Trends Endocrinol Metab 21(7):435–440. doi: 10.1016/j.tem.2010.02.006 PubMedCrossRefGoogle Scholar
  176. Rahman MM, Stuchlick O, El-Karim EG, Stuart R, Kipreos ET, Wells L (2010) Intracellular protein glycosylation modulates insulin mediated lifespan in C.elegans. Aging 2(10):678–690PubMedCentralPubMedGoogle Scholar
  177. Ratnappan R, Amrit FR, Chen SW, Gill H, Holden K, Ward J, Yamamoto KR, Olsen CP, Ghazi A (2014) Germline signals deploy NHR-49 to modulate fatty-acid beta-oxidation and desaturation in somatic tissues of C. elegans. PLoS Genet 10(12), e1004829. doi: 10.1371/journal.pgen.1004829 PubMedCentralPubMedCrossRefGoogle Scholar
  178. Rea SL, Ventura N, Johnson TE (2007) Relationship between mitochondrial electron transport chain dysfunction, development, and life extension in Caenorhabditis elegans. PLoS Biol 5(10), e259. doi: 10.1371/journal.pbio.0050259 PubMedCentralPubMedCrossRefGoogle Scholar
  179. Riera CE, Huising MO, Follett P, Leblanc M, Halloran J, Van Andel R, de Magalhaes Filho CD, Merkwirth C, Dillin A (2014) TRPV1 pain receptors regulate longevity and metabolism by neuropeptide signaling. Cell 157(5):1023–1036. doi: 10.1016/j.cell.2014.03.051 PubMedCrossRefGoogle Scholar
  180. Rizki G, Iwata TN, Li J, Riedel CG, Picard CL, Jan M, Murphy CT, Lee SS (2011) The evolutionarily conserved longevity determinants HCF-1 and SIR-2.1/SIRT1 collaborate to regulate DAF-16/FOXO. PLoS Genet 7(9), e1002235. doi: 10.1371/journal.pgen.1002235 PubMedCentralPubMedCrossRefGoogle Scholar
  181. Robida-Stubbs S, Glover-Cutter K, Lamming DW, Mizunuma M, Narasimhan SD, Neumann-Haefelin E, Sabatini DM, Blackwell TK (2012) TOR signaling and rapamycin influence longevity by regulating SKN-1/Nrf and DAF-16/FoxO. Cell Metab 15(5):713–724. doi: 10.1016/j.cmet.2012.04.007 PubMedCentralPubMedCrossRefGoogle Scholar
  182. Rogers AN, Chen D, McColl G, Czerwieniec G, Felkey K, Gibson BW, Hubbard A, Melov S, Lithgow GJ, Kapahi P (2011) Life span extension via eIF4G inhibition is mediated by posttranscriptional remodeling of stress response gene expression in C. elegans. Cell Metab 14(1):55–66. doi: 10.1016/j.cmet.2011.05.010 PubMedCentralPubMedCrossRefGoogle Scholar
  183. Rottiers V, Motola DL, Gerisch B, Cummins CL, Nishiwaki K, Mangelsdorf DJ, Antebi A (2006) Hormonal control of C. elegans dauer formation and life span by a Rieske-like oxygenase. Dev Cell 10(4):473–482. doi: 10.1016/j.devcel.2006.02.008 PubMedCrossRefGoogle Scholar
  184. Samuelson AV, Klimczak RR, Thompson DB, Carr CE, Ruvkun G (2007) Identification of Caenorhabditis elegans genes regulating longevity using enhanced RNAi-sensitive strains. Cold Spring Harb Symp Quant Biol 72:489–497. doi: 10.1101/sqb.2007.72.068 PubMedCrossRefGoogle Scholar
  185. Schiavi A, Torgovnick A, Kell A, Megalou E, Castelein N, Guccini I, Marzocchella L, Gelino S, Hansen M, Malisan F, Condo I, Bei R, Rea SL, Braeckman BP, Tavernarakis N, Testi R, Ventura N (2013) Autophagy induction extends lifespan and reduces lipid content in response to frataxin silencing in C. elegans. Exp Gerontol 48(2):191–201. doi: 10.1016/j.exger.2012.12.002 PubMedCentralPubMedCrossRefGoogle Scholar
  186. Schmeisser K, Mansfeld J, Kuhlow D, Weimer S, Priebe S, Heiland I, Birringer M, Groth M, Segref A, Kanfi Y, Price NL, Schmeisser S, Schuster S, Pfeiffer AF, Guthke R, Platzer M, Hoppe T, Cohen HY, Zarse K, Sinclair DA, Ristow M (2013) Role of sirtuins in lifespan regulation is linked to methylation of nicotinamide. Nat Chem Biol 9(11):693–700. doi: 10.1038/nchembio.1352 PubMedCentralPubMedCrossRefGoogle Scholar
  187. Schreiber MA, Pierce-Shimomura JT, Chan S, Parry D, McIntire SL (2010) Manipulation of behavioral decline in Caenorhabditis elegans with the Rag GTPase raga-1. PLoS Genet 6(5), e1000972. doi: 10.1371/journal.pgen.1000972 PubMedCentralPubMedCrossRefGoogle Scholar
  188. Scott BA, Avidan MS, Crowder CM (2002) Regulation of hypoxic death in C. elegans by the insulin/IGF receptor homolog DAF-2. Science 296(5577):2388–2391. doi: 10.1126/science.1072302 PubMedCrossRefGoogle Scholar
  189. Selman C, Tullet JM, Wieser D, Irvine E, Lingard SJ, Choudhury AI, Claret M, Al-Qassab H, Carmignac D, Ramadani F, Woods A, Robinson IC, Schuster E, Batterham RL, Kozma SC, Thomas G, Carling D, Okkenhaug K, Thornton JM, Partridge L, Gems D, Withers DJ (2009) Ribosomal protein S6 kinase 1 signaling regulates mammalian life span. Science 326(5949):140–144. doi: 10.1126/science.1177221 PubMedCrossRefGoogle Scholar
  190. Semenza GL (2012) Hypoxia-inducible factors in physiology and medicine. Cell 148(3):399–408. doi: 10.1016/j.cell.2012.01.021 PubMedCentralPubMedCrossRefGoogle Scholar
  191. Seo K, Choi E, Lee D, Jeong DE, Jang SK, Lee SJ (2013) Heat shock factor 1 mediates the longevity conferred by inhibition of TOR and insulin/IGF-1 signaling pathways in C. elegans. Aging Cell 12(6):1073–1081. doi: 10.1111/acel.12140 PubMedCrossRefGoogle Scholar
  192. Shaw WM, Luo S, Landis J, Ashraf J, Murphy CT (2007) The C. elegans TGF-beta dauer pathway regulates longevity via insulin signaling. Curr Biol 17(19):1635–1645. doi: 10.1016/j.cub.2007.08.058 PubMedCentralPubMedCrossRefGoogle Scholar
  193. Sheaffer KL, Updike DL, Mango SE (2008) The target of rapamycin pathway antagonizes pha-4/FoxA to control development and aging. Curr Biol 18(18):1355–1364. doi: 10.1016/j.cub.2008.07.097 PubMedCentralPubMedCrossRefGoogle Scholar
  194. Shen Y, Wollam J, Magner D, Karalay O, Antebi A (2012) A steroid receptor-microRNA switch regulates life span in response to signals from the gonad. Science 338(6113):1472–1476. doi: 10.1126/science.1228967 PubMedCentralPubMedCrossRefGoogle Scholar
  195. Smith-Vikos T, de Lencastre A, Inukai S, Shlomchik M, Holtrup B, Slack FJ (2014) MicroRNAs mediate dietary-restriction-induced longevity through PHA-4/FOXA and SKN-1/Nrf transcription factors. Curr Biol 24(19):2238–2246. doi: 10.1016/j.cub.2014.08.013 PubMedCentralPubMedCrossRefGoogle Scholar
  196. Soukas AA, Kane EA, Carr CE, Melo JA, Ruvkun G (2009) Rictor/TORC2 regulates fat metabolism, feeding, growth, and life span in Caenorhabditis elegans. Genes Dev 23(4):496–511. doi: 10.1101/gad.1775409 PubMedCentralPubMedCrossRefGoogle Scholar
  197. Stanfel MN, Shamieh LS, Kaeberlein M, Kennedy BK (2009) The TOR pathway comes of age. Biochim Biophys Acta 1790(10):1067–1074. doi: 10.1016/j.bbagen.2009.06.007 PubMedCentralPubMedCrossRefGoogle Scholar
  198. Steinkraus KA, Smith ED, Davis C, Carr D, Pendergrass WR, Sutphin GL, Kennedy BK, Kaeberlein M (2008) Dietary restriction suppresses proteotoxicity and enhances longevity by an hsf-1-dependent mechanism in Caenorhabditis elegans. Aging Cell 7(3):394–404. doi: 10.1111/j.1474-9726.2008.00385.x PubMedCentralPubMedCrossRefGoogle Scholar
  199. Syntichaki P, Troulinaki K, Tavernarakis N (2007) eIF4E function in somatic cells modulates ageing in Caenorhabditis elegans. Nature 445(7130):922–926. doi: 10.1038/nature05603 PubMedCrossRefGoogle Scholar
  200. Takahashi Y, Daitoku H, Hirota K, Tamiya H, Yokoyama A, Kako K, Nagashima Y, Nakamura A, Shimada T, Watanabe S, Yamagata K, Yasuda K, Ishii N, Fukamizu A (2011) Asymmetric arginine dimethylation determines life span in C. elegans by regulating forkhead transcription factor DAF-16. Cell Metab 13(5):505–516. doi: 10.1016/j.cmet.2011.03.017 PubMedCrossRefGoogle Scholar
  201. Taylor RC, Dillin A (2013) XBP-1 is a cell-nonautonomous regulator of stress resistance and longevity. Cell 153(7):1435–1447. doi: 10.1016/j.cell.2013.05.042 PubMedCrossRefGoogle Scholar
  202. Tepper RG, Ashraf J, Kaletsky R, Kleemann G, Murphy CT, Bussemaker HJ (2013) PQM-1 complements DAF-16 as a key transcriptional regulator of DAF-2-mediated development and longevity. Cell 154(3):676–690. doi: 10.1016/j.cell.2013.07.006 PubMedCentralPubMedCrossRefGoogle Scholar
  203. Thondamal M, Witting M, Schmitt-Kopplin P, Aguilaniu H (2014) Steroid hormone signalling links reproduction to lifespan in dietary-restricted Caenorhabditis elegans. Nat Commun 5:4879. doi: 10.1038/ncomms5879 PubMedCrossRefGoogle Scholar
  204. Thyagarajan B, Blaszczak AG, Chandler KJ, Watts JL, Johnson WE, Graves BJ (2010) ETS-4 is a transcriptional regulator of life span in Caenorhabditis elegans. PLoS Genet 6(9), e1001125. doi: 10.1371/journal.pgen.1001125 PubMedCentralPubMedCrossRefGoogle Scholar
  205. Tissenbaum HA, Guarente L (2001) Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature 410(6825):227–230. doi: 10.1038/35065638 PubMedCrossRefGoogle Scholar
  206. Tonsaker T, Pratt RM, McGhee JD (2012) Re-evaluating the role of ELT-3 in a GATA transcription factor circuit proposed to guide aging in C. elegans. Mech Ageing Dev 133(1):50–53. doi: 10.1016/j.mad.2011.09.006 PubMedCrossRefGoogle Scholar
  207. Torgovnick A, Schiavi A, Testi R, Ventura N (2010) A role for p53 in mitochondrial stress response control of longevity in C. elegans. Exp Gerontol 45(7–8):550–557. doi: 10.1016/j.exger.2010.02.007 PubMedCrossRefGoogle Scholar
  208. Toth ML, Sigmond T, Borsos E, Barna J, Erdelyi P, Takacs-Vellai K, Orosz L, Kovacs AL, Csikos G, Sass M, Vellai T (2008) Longevity pathways converge on autophagy genes to regulate life span in Caenorhabditis elegans. Autophagy 4(3):330–338PubMedCrossRefGoogle Scholar
  209. Tsang WY, Sayles LC, Grad LI, Pilgrim DB, Lemire BD (2001) Mitochondrial respiratory chain deficiency in Caenorhabditis elegans results in developmental arrest and increased life span. J Biol Chem 276(34):32240–32246. doi: 10.1074/jbc.M103999200 PubMedCrossRefGoogle Scholar
  210. Tullet JM, Araiz C, Sanders MJ, Au C, Benedetto A, Papatheodorou I, Clark E, Schmeisser K, Jones D, Schuster EF, Thornton JM, Gems D (2014) DAF-16/FoxO directly regulates an atypical AMP-activated protein kinase gamma isoform to mediate the effects of insulin/IGF-1 signaling on aging in Caenorhabditis elegans. PLoS Genet 10(2), e1004109. doi: 10.1371/journal.pgen.1004109 PubMedCentralPubMedCrossRefGoogle Scholar
  211. Tullet JM, Hertweck M, An JH, Baker J, Hwang JY, Liu S, Oliveira RP, Baumeister R, Blackwell TK (2008) Direct inhibition of the longevity-promoting factor SKN-1 by insulin-like signaling in C. elegans. Cell 132(6):1025–1038. doi: 10.1016/j.cell.2008.01.030 PubMedCentralPubMedCrossRefGoogle Scholar
  212. van der Horst A, Schavemaker JM, Pellis-van Berkel W, Burgering BM (2007) The Caenorhabditis elegans nicotinamidase PNC-1 enhances survival. Mech Ageing Dev 128(4):346–349. doi: 10.1016/j.mad.2007.01.004 PubMedCrossRefGoogle Scholar
  213. Van Gilst MR, Hadjivassiliou H, Jolly A, Yamamoto KR (2005) Nuclear hormone receptor NHR-49 controls fat consumption and fatty acid composition in C. elegans. PLoS Biol 3(2), e53. doi: 10.1371/journal.pbio.0030053 PubMedCentralPubMedCrossRefGoogle Scholar
  214. Van Raamsdonk JM, Hekimi S (2009) Deletion of the mitochondrial superoxide dismutase sod-2 extends lifespan in Caenorhabditis elegans. PLoS Genet 5(2), e1000361. doi: 10.1371/journal.pgen.1000361 PubMedCentralPubMedCrossRefGoogle Scholar
  215. Van Raamsdonk JM, Hekimi S (2012) Superoxide dismutase is dispensable for normal animal lifespan. Proc Natl Acad Sci U S A 109(15):5785–5790. doi: 10.1073/pnas.1116158109 PubMedCentralPubMedCrossRefGoogle Scholar
  216. Vellai T, Takacs-Vellai K, Zhang Y, Kovacs AL, Orosz L, Muller F (2003) Genetics: influence of TOR kinase on lifespan in C. elegans. Nature 426(6967):620. doi: 10.1038/426620a PubMedCrossRefGoogle Scholar
  217. Ventura N, Rea S, Henderson ST, Condo I, Johnson TE, Testi R (2005) Reduced expression of frataxin extends the lifespan of Caenorhabditis elegans. Aging Cell 4(2):109–112PubMedCrossRefGoogle Scholar
  218. Ventura N, Rea SL, Schiavi A, Torgovnick A, Testi R, Johnson TE (2009) p53/CEP-1 increases or decreases lifespan, depending on level of mitochondrial bioenergetic stress. Aging Cell 8(4):380–393. doi: 10.1111/j.1474-9726.2009.00482.x PubMedCentralPubMedCrossRefGoogle Scholar
  219. Viswanathan M, Guarente L (2011) Regulation of Caenorhabditis elegans lifespan by sir-2.1 transgenes. Nature 477(7365):E1–E2. doi: 10.1038/nature10440 PubMedCrossRefGoogle Scholar
  220. Vora M, Shah M, Ostafi S, Onken B, Xue J, Ni JZ, Gu S, Driscoll M (2013) Deletion of microRNA-80 activates dietary restriction to extend C. elegans healthspan and lifespan. PLoS Genet 9(8), e1003737. doi: 10.1371/journal.pgen.1003737 PubMedCentralPubMedCrossRefGoogle Scholar
  221. Walter L, Baruah A, Chang HW, Pace HM, Lee SS (2011) The homeobox protein CEH-23 mediates prolonged longevity in response to impaired mitochondrial electron transport chain in C. elegans. PLoS Biol 9(6), e1001084. doi: 10.1371/journal.pbio.1001084 PubMedCentralPubMedCrossRefGoogle Scholar
  222. Wang J, Robida-Stubbs S, Tullet JM, Rual JF, Vidal M, Blackwell TK (2010) RNAi screening implicates a SKN-1-dependent transcriptional response in stress resistance and longevity deriving from translation inhibition. PLoS Genet 6(8). doi: 10.1371/journal.pgen.1001048
  223. Wang MC, O'Rourke EJ, Ruvkun G (2008) Fat metabolism links germline stem cells and longevity in C. elegans. Science 322(5903):957–960. doi: 10.1126/science.1162011 PubMedCentralPubMedCrossRefGoogle Scholar
  224. Wang Y, Tissenbaum HA (2006) Overlapping and distinct functions for a Caenorhabditis elegans SIR2 and DAF-16/FOXO. Mech Ageing Dev 127(1):48–56. doi: 10.1016/j.mad.2005.09.005 PubMedCrossRefGoogle Scholar
  225. Wang Y, Oh SW, Deplancke B, Luo J, Walhout AJ, Tissenbaum HA (2006) C. elegans 14-3-3 proteins regulate life span and interact with SIR-2.1 and DAF-16/FOXO. Mech Ageing Dev 127(9):741–747. doi: 10.1016/j.mad.2006.05.005 PubMedCrossRefGoogle Scholar
  226. Wolff S, Ma H, Burch D, Maciel GA, Hunter T, Dillin A (2006) SMK-1, an essential regulator of DAF-16-mediated longevity. Cell 124(5):1039–1053. doi: 10.1016/j.cell.2005.12.042 PubMedCrossRefGoogle Scholar
  227. Wolkow CA, Munoz MJ, Riddle DL, Ruvkun G (2002) Insulin receptor substrate and p55 orthologous adaptor proteins function in the Caenorhabditis elegans daf-2/insulin-like signaling pathway. J Biol Chem 277(51):49591–49597. doi: 10.1074/jbc.M207866200 PubMedCrossRefGoogle Scholar
  228. Wollam J, Magner DB, Magomedova L, Rass E, Shen Y, Rottiers V, Habermann B, Cummins CL, Antebi A (2012) A novel 3-hydroxysteroid dehydrogenase that regulates reproductive development and longevity. PLoS Biol 10(4), e1001305. doi: 10.1371/journal.pbio.1001305 PubMedCentralPubMedCrossRefGoogle Scholar
  229. Wong A, Boutis P, Hekimi S (1995) Mutations in the clk-1 gene of Caenorhabditis elegans affect developmental and behavioral timing. Genetics 139(3):1247–1259PubMedCentralPubMedGoogle Scholar
  230. Xiao R, Zhang B, Dong Y, Gong J, Xu T, Liu J, Xu XZ (2013) A genetic program promotes C. elegans longevity at cold temperatures via a thermosensitive TRP channel. Cell 152(4):806–817. doi: 10.1016/j.cell.2013.01.020 PubMedCentralPubMedCrossRefGoogle Scholar
  231. Xu X, Kim SK (2012) The GATA transcription factor egl-27 delays aging by promoting stress resistance in Caenorhabditis elegans. PLoS Genet 8(12), e1003108. doi: 10.1371/journal.pgen.1003108 PubMedCentralPubMedCrossRefGoogle Scholar
  232. Yamawaki TM, Berman JR, Suchanek-Kavipurapu M, McCormick M, Gaglia MM, Lee SJ, Kenyon C (2010) The somatic reproductive tissues of C. elegans promote longevity through steroid hormone signaling. PLoS Biol 8(8). doi: 10.1371/journal.pbio.1000468
  233. Yang CC, Chen D, Lee SS, Walter L (2011) The dynamin-related protein DRP-1 and the insulin signaling pathway cooperate to modulate Caenorhabditis elegans longevity. Aging Cell 10(4):724–728. doi: 10.1111/j.1474-9726.2011.00711.x PubMedCentralPubMedCrossRefGoogle Scholar
  234. Yang J, Chen D, He Y, Melendez A, Feng Z, Hong Q, Bai X, Li Q, Cai G, Wang J, Chen X (2013) MiR-34 modulates Caenorhabditis elegans lifespan via repressing the autophagy gene atg9. Age (Dordr) 35(1):11–22. doi: 10.1007/s11357-011-9324-3 CrossRefGoogle Scholar
  235. Yang W, Hekimi S (2010a) A mitochondrial superoxide signal triggers increased longevity in Caenorhabditis elegans. PLoS Biol 8(12), e1000556. doi: 10.1371/journal.pbio.1000556 PubMedCentralPubMedCrossRefGoogle Scholar
  236. Yang W, Hekimi S (2010b) Two modes of mitochondrial dysfunction lead independently to lifespan extension in Caenorhabditis elegans. Aging Cell 9(3):433–447, doi:ACE571 [pii]PubMedCrossRefGoogle Scholar
  237. Yee C, Yang W, Hekimi S (2014) The Intrinsic Apoptosis Pathway Mediates the Pro-Longevity Response to Mitochondrial ROS in C. elegans. Cell 157(4):897–909. doi: 10.1016/j.cell.2014.02.055 PubMedCentralPubMedCrossRefGoogle Scholar
  238. Zarse K, Schulz TJ, Birringer M, Ristow M (2007) Impaired respiration is positively correlated with decreased life span in Caenorhabditis elegans models of Friedreich Ataxia. FASEB J 21(4):1271–1275. doi: 10.1096/fj.06-6994com PubMedCrossRefGoogle Scholar
  239. Zhang Y, Xu J, Puscau C, Kim Y, Wang X, Alam H, Hu PJ (2008) Caenorhabditis elegans EAK-3 inhibits dauer arrest via nonautonomous regulation of nuclear DAF-16/FoxO activity. Dev Biol 315(2):290–302. doi: 10.1016/j.ydbio.2007.12.032 PubMedCentralPubMedCrossRefGoogle Scholar
  240. Zhang M, Poplawski M, Yen K, Cheng H, Bloss E, Zhu X, Patel H, Mobbs CV (2009a) Role of CBP and SATB-1 in aging, dietary restriction, and insulin-like signaling. PLoS Biol 7(11), e1000245. doi: 10.1371/journal.pbio.1000245 PubMedCentralPubMedCrossRefGoogle Scholar
  241. Zhang Y, Shao Z, Zhai Z, Shen C, Powell-Coffman JA (2009b) The HIF-1 hypoxia-inducible factor modulates lifespan in C. elegans. PLoS One 4(7), e6348. doi: 10.1371/journal.pone.0006348 PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 2015

Authors and Affiliations

  • Yujin Lee
    • 1
  • Seon Woo A. An
    • 1
  • Murat Artan
    • 2
  • Mihwa Seo
    • 3
    • 4
    • 5
  • Ara B. Hwang
    • 1
  • Dae-Eun Jeong
    • 1
  • Heehwa G. Son
    • 1
  • Wooseon Hwang
    • 1
  • Dongyeop Lee
    • 1
  • Keunhee Seo
    • 1
  • Ozlem Altintas
    • 3
  • Sangsoon Park
    • 1
  • Seung-Jae V. Lee
    • 1
    • 2
    • 3
    Email author
  1. 1.Department of Life SciencesPohang University of Science and TechnologyPohangSouth Korea
  2. 2.Information Technology Convergence EngineeringPohang University of Science and TechnologyPohangSouth Korea
  3. 3.School of Interdisciplinary Bioscience and BioengineeringPohang University of Science and TechnologyPohangSouth Korea
  4. 4.Center for Plant Aging Research, Institute for Basic ScienceDaegu Gyeongbuk Institute of Science and TechnologyDaeguSouth Korea
  5. 5.Department of New BiologyDaegu Gyeongbuk Institute of Science and TechnologyDaeguSouth Korea

Personalised recommendations