Skip to main content
SpringerLink
Log in

Longevity Regulation by Insulin/IGF-1 Signalling

  • Chapter
  • First Online:
Ageing: Lessons from C. elegans

Part of the book series: Healthy Ageing and Longevity ((HAL))

Abstract

For the past three decades, many ageing-regulatory pathways have been identified using C. elegans as a model organism. The insulin/insulin-like growth factor (IGF)-1 signalling (IIS) pathway is one of the most evolutionarily well-conserved ageing-regulatory pathways ranging from worms to mammals. Here, we review the molecular mechanism and the functional significance of IIS in C. elegans ageing. Specifically, we describe the roles of key components of IIS in ageing, systemic ageing regulation by IIS, and other known physiological functions of IIS that contribute to longevity. We also discuss possible implications of IIS in mammalian health and ageing.

*Author contributed equally with all other contributors.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 99.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Kenyon CJ (2010) The genetics of ageing. Nature 464(7288):504–512

    Article  CAS  PubMed  Google Scholar 

  2. Fontana L, Partridge L, Longo VD (2010) Extending healthy life span – from yeast to humans. Science (New York, NY) 328(5976):321–326

    Article  CAS  Google Scholar 

  3. Klass MR (1983) A method for the isolation of longevity mutants in the nematode C. elegans and initial results. Mech Ageing Dev 22(3–4):279–286

    Article  CAS  PubMed  Google Scholar 

  4. Friedman DB, Johnson TE (1988) Three mutants that extend both mean and maximum life span of the nematode, C. elegans, define the age-1 gene. J Gerontol 43(4):B102–B109

    Article  CAS  PubMed  Google Scholar 

  5. 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

    Article  CAS  PubMed  Google Scholar 

  6. Morris JZ, Tissenbaum HA, Ruvkun G (1996) A phosphatidylinositol-3-OH kinase family member regulating longevity and diapause in C. elegans. Nature 382(6591):536–539

    Article  CAS  PubMed  Google Scholar 

  7. Kimura KD, Tissenbaum HA, Liu Y, Ruvkun G (1997) daf-2, an insulin receptor-like gene that regulates longevity and diapause in C. elegans. Science (New York, NY) 277(5328):942–946

    Article  CAS  Google Scholar 

  8. 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 C. elegans. Genetics 141(4):1399–1406

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Murphy CT, Hu PJ (2013) Insulin/insulin-like growth factor signaling in C. elegans. WormBook Online Rev C elegans Biol:1–43

    Google Scholar 

  10. 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 C. elegans. Genes Dev 13(11):1438–1452

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Zhou K, Pandol S, Bokoch G, Traynor-Kaplan AE (1998) Disruption of Dictyostelium PI3K genes reduces [32P]phosphatidylinositol 3,4 bisphosphate and [32P]phosphatidylinositol trisphosphate levels, alters F-actin distribution and impairs pinocytosis. J Cell Sci 111(Pt 2):283–294

    CAS  PubMed  Google Scholar 

  12. Paradis S, Ruvkun G (1998) C. elegans Akt/PKB transduces insulin receptor-like signals from AGE-1 PI3 kinase to the DAF-16 transcription factor. Genes Dev 12(16):2488–2498

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Larsen PL, Albert PS, Riddle DL (1995) Genes that regulate both development and longevity in C. elegans. Genetics 139(4):1567–1583

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Gil EB, Malone Link E, Liu LX, Johnson CD, Lees JA (1999) Regulation of the insulin-like developmental pathway of C. elegans by a homolog of the PTEN tumor suppressor gene. Proc Natl Acad Sci U S A 96(6):2925–2930

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Ogg S, Ruvkun G (1998) The C. elegans PTEN homolog, DAF-18, acts in the insulin receptor-like metabolic signaling pathway. Mol Cell 2(6):887–893

    Article  CAS  PubMed  Google Scholar 

  16. Mihaylova VT, Borland CZ, Manjarrez L, Stern MJ, Sun H (1999) The PTEN tumor suppressor homolog in C. elegans regulates longevity and dauer formation in an insulin receptor-like signaling pathway. Proc Natl Acad Sci U S A 96(13):7427–7432

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Solari F, Bourbon-Piffaut A, Masse I, Payrastre B, Chan AM, Billaud M (2005) The human tumour suppressor PTEN regulates longevity and dauer formation in C. elegans. Oncogene 24(1):20–27

    Article  CAS  PubMed  Google Scholar 

  18. 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

    Article  CAS  PubMed  Google Scholar 

  19. 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 C. elegans. Science (New York, NY) 278(5341):1319–1322

    Article  CAS  Google Scholar 

  20. Lee SS, Kennedy S, Tolonen AC, Ruvkun G (2003) DAF-16 target genes that control C. elegans life-span and metabolism. Science (New York, NY) 300(5619):644–647

    Article  CAS  Google Scholar 

  21. 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 C. elegans. Nature 424(6946):277–283

    Article  CAS  PubMed  Google Scholar 

  22. McElwee J, Bubb K, Thomas JH (2003) Transcriptional outputs of the C. elegans forkhead protein DAF-16. Aging Cell 2(2):111–121

    Article  CAS  PubMed  Google Scholar 

  23. McElwee JJ, Schuster E, Blanc E, Thomas JH, Gems D (2004) Shared transcriptional signature in C. elegans Dauer larvae and long-lived daf-2 mutants implicates detoxification system in longevity assurance. J Biol Chem 279(43):44533–44543

    Article  CAS  PubMed  Google Scholar 

  24. 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Halaschek-Wiener J, Khattra JS, McKay S, Pouzyrev A, Stott JM, Yang GS, Holt RA, Jones SJ, Marra MA, Brooks-Wilson AR, Riddle DL (2005) Analysis of long-lived C. elegans daf-2 mutants using serial analysis of gene expression. Genome Res 15(5):603–615

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Henderson ST, Johnson TE (2001) daf-16 integrates developmental and environmental inputs to mediate aging in the nematode C. elegans. Curr Biol 11(24):1975–1980

    Article  CAS  PubMed  Google Scholar 

  27. Lin K, Hsin H, Libina N, Kenyon C (2001) Regulation of the C. elegans longevity protein DAF-16 by insulin/IGF-1 and germline signaling. Nat Genet 28(2):139–145

    Article  CAS  PubMed  Google Scholar 

  28. 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):1950–1957

    Article  CAS  PubMed  Google Scholar 

  29. Cahill CM, Tzivion G, Nasrin N, Ogg S, Dore J, Ruvkun G, Alexander-Bridges M (2001) Phosphatidylinositol 3-kinase signaling inhibits DAF-16 DNA binding and function via 14-3-3-dependent and 14-3-3-independent pathways. J Biol Chem 276(16):13402–13410

    Article  CAS  PubMed  Google Scholar 

  30. 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):577–588

    Article  CAS  PubMed  Google Scholar 

  31. Chen AT, Guo C, Dumas KJ, Ashrafi K, Hu PJ (2013) Effects of C. elegans sgk-1 mutations on lifespan, stress resistance, and DAF-16/FoxO regulation. Aging Cell 12(5):932–940

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. 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):3004–3009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Curtis R, O’Connor G, DiStefano PS (2006) Aging networks in C. elegans: AMP-activated protein kinase (aak-2) links multiple aging and metabolism pathways. Aging Cell 5(2):119–126

    Article  CAS  PubMed  Google Scholar 

  35. 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 C. elegans. PLoS Genet 10(2), e1004109

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. 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

    Article  CAS  PubMed  Google Scholar 

  38. Oh SW, Mukhopadhyay A, Svrzikapa N, Jiang F, Davis RJ, Tissenbaum HA (2005) JNK regulates lifespan in C. elegans by modulating nuclear translocation of forkhead transcription factor/DAF-16. Proc Natl Acad Sci U S A 102(12):4494–4499

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. 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

    Article  CAS  PubMed  Google Scholar 

  40. 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Zhang M, Poplawski M, Yen K, Cheng H, Bloss E, Zhu X, Patel H, Mobbs CV (2009) Role of CBP and SATB-1 in aging, dietary restriction, and insulin-like signaling. PLoS Biol 7(11), e1000245

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Chiang WC, Tishkoff DX, Yang B, Wilson-Grady J, Yu X, Mazer T, Eckersdorff M, Gygi SP, Lombard DB, Hsu AL (2012) C. elegans SIRT6/7 homolog SIR-2.4 promotes DAF-16 relocalization and function during stress. PLoS Genet 8(9), e1002948

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Tissenbaum HA, Guarente L (2001) Increased dosage of a sir-2 gene extends lifespan in C. elegans. Nature 410(6825):227–230

    Article  CAS  PubMed  Google Scholar 

  44. 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

    Article  CAS  PubMed  Google Scholar 

  45. 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Li W, Gao B, Lee SM, Bennett K, Fang D (2007) RLE-1, an E3 ubiquitin ligase, regulates C. elegans aging by catalyzing DAF-16 polyubiquitination. Dev Cell 12(2):235–246

    Article  CAS  PubMed  Google Scholar 

  48. Heimbucher T, Liu Z, Bossard C, McCloskey R, Carrano AC, Riedel CG, Tanasa B, Klammt C, Fonslow BR, Riera CE, Lillemeier BF, Kemphues K, Yates JR 3rd, O’Shea C, Hunter T, Dillin A (2015) The deubiquitylase MATH-33 controls DAF-16 stability and function in metabolism and longevity. Cell Metab 22(1):151–163

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Ghazi A, Henis-Korenblit S, Kenyon C (2007) Regulation of C. elegans lifespan by a proteasomal E3 ligase complex. Proc Natl Acad Sci U S A 104(14):5947–5952

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Chondrogianni N, Georgila K, Kourtis N, Tavernarakis N, Gonos ES (2015) 20S proteasome activation promotes life span extension and resistance to proteotoxicity in C. elegans. FASEB J 29(2):611–622

    Article  CAS  PubMed  Google Scholar 

  51. Li J, Tewari M, Vidal M, Lee SS (2007) The 14-3-3 protein FTT-2 regulates DAF-16 in C. elegans. Dev Biol 301(1):82–91

    Article  CAS  PubMed  Google Scholar 

  52. 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

    Article  CAS  PubMed  Google Scholar 

  53. 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Kwon ES, Narasimhan SD, Yen K, Tissenbaum HA (2010) A new DAF-16 isoform regulates longevity. Nature 466(7305):498–502

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Bansal A, Kwon ES, Conte D Jr, Liu H, Gilchrist MJ, MacNeil LT, Tissenbaum HA (2014) Transcriptional regulation of C. elegans FOXO/DAF-16 modulates lifespan. Longev Healthspan 3:5

    Article  PubMed  PubMed Central  Google Scholar 

  56. Furuyama T, Nakazawa T, Nakano I, Mori N (2000) Identification of the differential distribution patterns of mRNAs and consensus binding sequences for mouse DAF-16 homologues. Biochem J 349(Pt 2):629–634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Schuster E, McElwee JJ, Tullet JM, Doonan R, Matthijssens F, Reece-Hoyes JS, Hope IA, Vanfleteren JR, Thornton JM, Gems D (2010) DamID in C. elegans reveals longevity-associated targets of DAF-16/FoxO. Mol Syst Biol 6:399

    Article  PubMed  PubMed Central  Google Scholar 

  59. 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Zhang P, Judy M, Lee SJ, Kenyon C (2013) Direct and indirect gene regulation by a life-extending FOXO protein in C. elegans: roles for GATA factors and lipid gene regulators. Cell Metab 17(1):85–100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Thyagarajan B, Blaszczak AG, Chandler KJ, Watts JL, Johnson WE, Graves BJ (2010) ETS-4 is a transcriptional regulator of life span in C. elegans. PLoS Genet 6(9), e1001125

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Seo M, Seo K, Hwang W, Koo HJ, Hahm JH, Yang JS, Han SK, Hwang D, Kim S, Jang SK, Lee Y, Nam HG, Lee SJ (2015) RNA helicase HEL-1 promotes longevity by specifically activating DAF-16/FOXO transcription factor signaling in C. elegans. Proc Natl Acad Sci U S A 112(31):E4246–E4255

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. 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

    Article  CAS  PubMed  Google Scholar 

  65. Riedel CG, Dowen RH, Lourenco GF, Kirienko NV, Heimbucher T, West JA, Bowman SK, Kingston RE, Dillin A, Asara JM, Ruvkun G (2013) DAF-16 employs the chromatin remodeller SWI/SNF to promote stress resistance and longevity. Nat Cell Biol 15(5):491–501

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Morimoto RI (2011) The heat shock response: systems biology of proteotoxic stress in aging and disease. Cold Spring Harb Symp Quant Biol 76:91–99

    Article  CAS  PubMed  Google Scholar 

  67. Hsu AL, Murphy CT, Kenyon C (2003) Regulation of aging and age-related disease by DAF-16 and heat-shock factor. Science (New York, NY) 300(5622):1142–1145

    Google Scholar 

  68. Morley JF, Morimoto RI (2004) Regulation of longevity in C. elegans by heat shock factor and molecular chaperones. Mol Biol Cell 15(2):657–664

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Douglas PM, Baird NA, Simic MS, Uhlein S, McCormick MA, Wolff SC, Kennedy BK, Dillin A (2015) Heterotypic signals from neural HSF-1 separate thermotolerance from longevity. Cell Rep 12(7):1196–1204

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Volovik Y, Maman M, Dubnikov T, Bejerano-Sagie M, Joyce D, Kapernick EA, Cohen E, Dillin A (2012) Temporal requirements of heat shock factor-1 for longevity assurance. Aging Cell 11(3):491–499

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Dillin A, Crawford DK, Kenyon C (2002) Timing requirements for insulin/IGF-1 signaling in C. elegans. Science (New York, NY) 298(5594):830–834

    Article  CAS  Google Scholar 

  72. Amin J, Ananthan J, Voellmy R (1988) Key features of heat shock regulatory elements. Mol Cell Biol 8(9):3761–3769

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Walker GA, Lithgow GJ (2003) Lifespan extension in C. elegans by a molecular chaperone dependent upon insulin-like signals. Aging Cell 2(2):131–139

    Article  CAS  PubMed  Google Scholar 

  74. 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Baird NA, Douglas PM, Simic MS, Grant AR, Moresco JJ, Wolff SC, Yates JR 3rd, Manning G, Dillin A (2014) HSF-1-mediated cytoskeletal integrity determines thermotolerance and life span. Science (New York, NY) 346(6207):360–363

    Article  CAS  Google Scholar 

  76. Horikawa M, Sural S, Hsu AL, Antebi A (2015) Co-chaperone p23 regulates C. elegans lifespan in response to temperature. PLoS Genet 11(4), e1005023

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  77. 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

    Article  CAS  PubMed  Google Scholar 

  78. Blackwell TK, Steinbaugh MJ, Hourihan JM, Ewald CY, Isik M (2015) SKN-1/Nrf, stress responses, and aging in C. elegans. Free Radic Biol Med

    Google Scholar 

  79. An JH, Blackwell TK (2003) SKN-1 links C. elegans mesendodermal specification to a conserved oxidative stress response. Genes Dev 17(15):1882–1893

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. An JH, Vranas K, Lucke M, Inoue H, Hisamoto N, Matsumoto K, Blackwell TK (2005) Regulation of the C. elegans oxidative stress defense protein SKN-1 by glycogen synthase kinase-3. Proc Natl Acad Sci U S A 102(45):16275–16280

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Kahn NW, Rea SL, Moyle S, Kell A, Johnson TE (2008) Proteasomal dysfunction activates the transcription factor SKN-1 and produces a selective oxidative-stress response in C. elegans. Biochem J 409(1):205–213

    Article  CAS  PubMed  Google Scholar 

  83. Oliveira RP, Porter Abate J, Dilks K, Landis J, Ashraf J, Murphy CT, Blackwell TK (2009) Condition-adapted stress and longevity gene regulation by C. elegans SKN-1/Nrf. Aging Cell 8(5):524–541

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. 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)

    Google Scholar 

  85. Li X, Matilainen O, Jin C, Glover-Cutter KM, Holmberg CI, Blackwell TK (2011) Specific SKN-1/Nrf stress responses to perturbations in translation elongation and proteasome activity. PLoS Genet 7(6), e1002119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Ewald CY, Landis JN, Porter Abate J, Murphy CT, Blackwell TK (2015) Dauer-independent insulin/IGF-1-signalling implicates collagen remodelling in longevity. Nature 519(7541):97–101

    Article  CAS  PubMed  Google Scholar 

  87. White JG, Southgate E, Thomson JN, Brenner S (1986) The structure of the nervous system of the nematode C. elegans. Philos Trans R Soc Lond B Biol Sci 314(1165):1–340

    Article  CAS  PubMed  Google Scholar 

  88. 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

    Article  PubMed  PubMed Central  Google Scholar 

  89. Apfeld J, Kenyon C (1999) Regulation of lifespan by sensory perception in C. elegans. Nature 402(6763):804–809

    Article  CAS  PubMed  Google Scholar 

  90. Lee SJ, Kenyon C (2009) Regulation of the longevity response to temperature by thermosensory neurons in C. elegans. Curr Biol 19(9):715–722

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Alcedo J, Kenyon C (2004) Regulation of C. elegans longevity by specific gustatory and olfactory neurons. Neuron 41(1):45–55

    Article  CAS  PubMed  Google Scholar 

  92. Lans H, Jansen G (2007) Multiple sensory G proteins in the olfactory, gustatory and nociceptive neurons modulate longevity in C. elegans. Dev Biol 303(2):474–482

    Article  CAS  PubMed  Google Scholar 

  93. Artan M, Jeong DE, Lee D, Kim YI, Son HG, Husain Z, Kim J, Altintas O, Kim K, Alcedo J, Lee SJ (2016) Food-derived sensory cues modulate longevity via distinct neuroendocrine insulin-like peptides. Genes Dev 30(9):1047–1057

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Ailion M, Inoue T, Weaver CI, Holdcraft RW, Thomas JH (1999) Neurosecretory control of aging in C. elegans. Proc Natl Acad Sci U S A 96(13):7394–7397

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Lanjuin A, Sengupta P (2002) Regulation of chemosensory receptor expression and sensory signaling by the KIN-29 Ser/Thr kinase. Neuron 33(3):369–381

    Article  CAS  PubMed  Google Scholar 

  96. Lee BH, Ashrafi K (2008) A TRPV channel modulates C. elegans neurosecretion, larval starvation survival, and adult lifespan. PLoS Genet 4(10), e1000213

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  97. Hahm JH, Kim S, Paik YK (2009) Endogenous cGMP regulates adult longevity via the insulin signaling pathway in C. elegans. Aging Cell 8(4):473–483

    Article  CAS  PubMed  Google Scholar 

  98. Riera CE, Huising MO, Follett P, Leblanc M, Halloran J, Van Andel R, de Magalhaes CD, Merkwirth C, Dillin A (2014) TRPV1 pain receptors regulate longevity and metabolism by neuropeptide signaling. Cell 157(5):1023–1036

    Article  CAS  PubMed  Google Scholar 

  99. 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  100. 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 C. elegans. PLoS Genet 8(12), e1003133

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Zhang B, Xiao R, Ronan EA, He Y, Hsu AL, Liu J, Xu XZ (2015) Environmental temperature differentially modulates C. elegans longevity through a thermosensitive TRP channel. Cell Rep 11(9):1414–1424

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Duret L, Guex N, Peitsch MC, Bairoch A (1998) New insulin-like proteins with atypical disulfide bond pattern characterized in C. elegans by comparative sequence analysis and homology modeling. Genome Res 8(4):348–353

    CAS  PubMed  Google Scholar 

  103. Gregoire FM, Chomiki N, Kachinskas D, Warden CH (1998) Cloning and developmental regulation of a novel member of the insulin-like gene family in C. elegans. Biochem Biophys Res Commun 249(2):385–390

    Article  CAS  PubMed  Google Scholar 

  104. 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 C. elegans. Biochem Biophys Res Commun 273(2):431–436

    Article  CAS  PubMed  Google Scholar 

  105. Pierce SB, Costa M, Wisotzkey R, Devadhar S, Homburger SA, Buchman AR, Ferguson KC, Heller J, Platt DM, Pasquinelli AA (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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Li W, Kennedy SG, Ruvkun G (2003) daf-28 encodes a C. elegans insulin superfamily member that is regulated by environmental cues and acts in the DAF-2 signaling pathway. Genes Dev 17(7):844–858

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Husson SJ, Mertens I, Janssen T, Lindemans M, Schoofs L (2007) Neuropeptidergic signaling in the nematode C. elegans. Prog Neurobiol 82(1):33–55

    Article  CAS  PubMed  Google Scholar 

  108. Hua Q-x, Nakagawa SH, Wilken J, Ramos RR, Jia W, Bass J, Weiss MA (2003) A divergent INS protein in Caenorhabditis elegans structurally resembles human insulin and activates the human insulin receptor. Genes Dev 17(7):826–831

    Google Scholar 

  109. Murphy CT, Lee S-J, Kenyon C (2007) Tissue entrainment by feedback regulation of insulin gene expression in the endoderm of C. elegans. Proc Natl Acad Sci 104(48):19046–19050

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Lin CHA, Tomioka M, Pereira S, Sellings L, Iino Y, van der Kooy D (2010) Insulin signaling plays a dual role in C. elegans memory acquisition and memory retrieval. J Neurosci 30(23):8001–8011

    Article  CAS  PubMed  Google Scholar 

  111. Cornils A, Gloeck M, Chen Z, Zhang Y, Alcedo J (2011) Specific insulin-like peptides encode sensory information to regulate distinct developmental processes. Development 138(6):1183–1193

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Matsunaga Y, Gengyo-Ando K, Mitani S, Iwasaki T, Kawano T (2012) Physiological function, expression pattern, and transcriptional regulation of a C. elegans insulin-like peptide, INS-18. Biochem Biophys Res Commun 423(3):478–483

    Article  CAS  PubMed  Google Scholar 

  113. Matsunaga Y, Nakajima K, Gengyo-Ando K, Mitani S, Iwasaki T, Kawano T (2012) A C. elegans insulin-like peptide, INS-17: its physiological function and expression pattern. Biosci Biotechnol Biochem 76(11):2168–2172

    Article  CAS  PubMed  Google Scholar 

  114. Kulalert W, Kim DH (2013) The unfolded protein response in a pair of sensory neurons promotes entry of C. elegans into dauer diapause. Curr Biol 23(24):2540–2545

    Article  CAS  PubMed  Google Scholar 

  115. Leinwand SG, Chalasani SH (2013) Neuropeptide signaling remodels chemosensory circuit composition in C. elegans. Nat Neurosci 16(10):1461–1467

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Chen Z, Hendricks M, Cornils A, Maier W, Alcedo J, Zhang Y (2013) Two insulin-like peptides antagonistically regulate aversive olfactory learning in C. elegans. Neuron 77(3):572–585

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Hung WL, Wang Y, Chitturi J, Zhen M (2014) A C. elegans developmental decision requires insulin signaling-mediated neuron-intestine communication. Development 141(8):1767–1779

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Malone EA, Inoue T, Thomas JH (1996) Genetic analysis of the roles of daf-28 and age-1 in regulating C. elegans Dauer formation. Genetics 143(3):1193–1205

    CAS  PubMed  PubMed Central  Google Scholar 

  119. Ohta A, Ujisawa T, Sonoda S, Kuhara A (2014) Light and pheromone-sensing neurons regulates cold habituation through insulin signalling in C. elegans. Nature Commun 5:4412

    Google Scholar 

  120. Chen Y, Baugh LR (2014) Ins-4 and daf-28 function redundantly to regulate C. elegans L1 arrest. Dev Biol 394(2):314–326

    Article  CAS  PubMed  Google Scholar 

  121. de Abreu DAF, Caballero A, Fardel P, Stroustrup N, Chen Z, Lee K, Keyes WD, Nash ZM, López-Moyado IF, Vaggi F (2014) An insulin-to-insulin regulatory network orchestrates phenotypic specificity in development and physiology. PLoS Genet 10(3), e1004225

    Article  CAS  Google Scholar 

  122. Ritter AD, Shen Y, Bass JF, Jeyaraj S, Deplancke B, Mukhopadhyay A, Xu J, Driscoll M, Tissenbaum HA, Walhout AJ (2013) Complex expression dynamics and robustness in C. elegans insulin networks. Genome Res 23(6):954–965

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Nelson DW, Padgett RW (2003) Insulin worms its way into the spotlight. Genes Dev 17(7):813–818

    Article  CAS  PubMed  Google Scholar 

  124. Michaelson D, Korta DZ, Capua Y, Hubbard EJA (2010) Insulin signaling promotes germline proliferation in C. elegans. Development 137(4):671–680

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Apfeld J, Kenyon C (1998) Cell nonautonomy of C. elegans daf-2 function in the regulation of diapause and life span. Cell 95(2):199–210

    Article  CAS  PubMed  Google Scholar 

  126. Wolkow CA, Kimura KD, Lee M-S, Ruvkun G (2000) Regulation of C. elegans life-span by insulin-like signaling in the nervous system. Science (New York, NY) 290(5489):147–150

    Article  CAS  Google Scholar 

  127. Masse I, Molin L, Billaud M, Solari F (2005) Lifespan and dauer regulation by tissue-specific activities of C. elegans DAF-18. Dev Biol 286(1):91–101

    Article  CAS  PubMed  Google Scholar 

  128. Libina N, Berman JR, Kenyon C (2003) Tissue-specific activities of C. elegans DAF-16 in the regulation of lifespan. Cell 115(4):489–502

    Article  CAS  PubMed  Google Scholar 

  129. Corsi AK, Wightman B, Chalfie M (2015) A transparent window into biology: a primer on C. elegans. WormBook: Online Rev C elegans Biol:1–31

    Google Scholar 

  130. 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):7540–7544

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. 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 C. elegans. Genetics 150(1):129–155

    CAS  PubMed  PubMed Central  Google Scholar 

  132. Larsen PL (1993) Aging and resistance to oxidative damage in C. elegans. Proc Natl Acad Sci U S A 90(19):8905–8909

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Vanfleteren JR (1993) Oxidative stress and ageing in C. elegans. Biochem J 292(Pt 2):605–608

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Honda Y, Honda S (1999) The daf-2 gene network for longevity regulates oxidative stress resistance and Mn-superoxide dismutase gene expression in C. elegans. FASEB J 13(11):1385–1393

    CAS  PubMed  Google Scholar 

  135. 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

    Article  CAS  PubMed  Google Scholar 

  136. Scott BA, Avidan MS, Crowder CM (2002) Regulation of hypoxic death in C. elegans by the insulin/IGF receptor homolog DAF-2. Science (New York, NY) 296(5577):2388–2391

    Article  CAS  Google Scholar 

  137. Mabon ME, Scott BA, Crowder CM (2009) Divergent mechanisms controlling hypoxic sensitivity and lifespan by the DAF-2/insulin/IGF-receptor pathway. PLoS ONE 4(11), e7937

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  138. Barsyte D, Lovejoy DA, Lithgow GJ (2001) Longevity and heavy metal resistance in daf-2 and age-1 long-lived mutants of C. elegans. FASEB J 15(3):627–634

    Article  CAS  PubMed  Google Scholar 

  139. Murakami S, Johnson TE (1996) A genetic pathway conferring life extension and resistance to UV stress in C. elegans. Genetics 143(3):1207–1218

    CAS  PubMed  PubMed Central  Google Scholar 

  140. 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 C. elegans. Proc Natl Acad Sci U S A 99(16):10417–10422

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  141. Burkewitz K, Choe K, Strange K (2011) Hypertonic stress induces rapid and widespread protein damage in C. elegans. Am J Physiol Cell Physiol 301(3):C566–C576

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Mueller MM, Castells-Roca L, Babu V, Ermolaeva MA, Muller RU, Frommolt P, Williams AB, Greiss S, Schneider JI, Benzing T, Schermer B, Schumacher B (2014) DAF-16/FOXO and EGL-27/GATA promote developmental growth in response to persistent somatic DNA damage. Nat Cell Biol 16(12):1168–1179

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. McColl G, Rogers AN, Alavez S, Hubbard AE, Melov S, Link CD, Bush AI, Kapahi P, Lithgow GJ (2010) Insulin-like signaling determines survival during stress via posttranscriptional mechanisms in C. elegans. Cell Metab 12(3):260–272

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. 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 (New York, NY) 308(5725):1181–1184

    Article  CAS  Google Scholar 

  145. Landis JN, Murphy CT (2010) Integration of diverse inputs in the regulation of C. elegans DAF-16/FOXO. Dev Dyn 239(5):1405–1412

    CAS  PubMed  Google Scholar 

  146. Curran SP, Wu X, Riedel CG, Ruvkun G (2009) A soma-to-germline transformation in long-lived C. elegans mutants. Nature 459(7250):1079–1084

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. 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 (New York, NY) 300(5627):1921

    Article  CAS  Google Scholar 

  148. Kerry S, TeKippe M, Gaddis NC, Aballay A (2006) GATA transcription factor required for immunity to bacterial and fungal pathogens. PLoS ONE 1, e77

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  149. Kim DH, Feinbaum R, Alloing G, Emerson FE, Garsin DA, Inoue H, Tanaka-Hino M, Hisamoto N, Matsumoto K, Tan MW, Ausubel FM (2002) A conserved p38 MAP kinase pathway in C. elegans innate immunity. Science (New York, NY) 297(5581):623–626

    Article  CAS  Google Scholar 

  150. Troemel ER, Chu SW, Reinke V, Lee SS, Ausubel FM, Kim DH (2006) p38 MAPK regulates expression of immune response genes and contributes to longevity in C. elegans. PLoS Genet 2(11), e183

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  151. Evans EA, Chen WC, Tan MW (2008) The DAF-2 insulin-like signaling pathway independently regulates aging and immunity in C. elegans. Aging Cell 7(6):879–893

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Singh V, Aballay A (2006) Heat-shock transcription factor (HSF)-1 pathway required for C. elegans immunity. Proc Natl Acad Sci U S A 103(35):13092–13097

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Papp D, Csermely P, Soti C (2012) A role for SKN-1/Nrf in pathogen resistance and immunosenescence in C. elegans. PLoS Pathog 8(4), e1002673

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Wang D, Ruvkun G (2004) Regulation of C. elegans RNA interference by the daf-2 insulin stress and longevity signaling pathway. Cold Spring Harb Symp Quant Biol 69:429–431

    Article  CAS  PubMed  Google Scholar 

  155. Schott DH, Cureton DK, Whelan SP, Hunter CP (2005) An antiviral role for the RNA interference machinery in C. elegans. Proc Natl Acad Sci U S A 102(51):18420–18424

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Wilkins C, Dishongh R, Moore SC, Whitt MA, Chow M, Machaca K (2005) RNA interference is an antiviral defence mechanism in C. elegans. Nature 436(7053):1044–1047

    Article  CAS  PubMed  Google Scholar 

  157. Felix MA, Ashe A, Piffaretti J, Wu G, Nuez I, Belicard T, Jiang Y, Zhao G, Franz CJ, Goldstein LD, Sanroman M, Miska EA, Wang D (2011) Natural and experimental infection of C. nematodes by novel viruses related to nodaviruses. PLoS Biol 9(1), e1000586

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Faber PW, Alter JR, MacDonald ME, Hart AC (1999) Polyglutamine-mediated dysfunction and apoptotic death of a C. elegans sensory neuron. Proc Natl Acad Sci U S A 96(1):179–184

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Link CD (1995) Expression of human beta-amyloid peptide in transgenic C. elegans. Proc Natl Acad Sci U S A 92(20):9368–9372

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Kraemer BC, Zhang B, Leverenz JB, Thomas JH, Trojanowski JQ, Schellenberg GD (2003) Neurodegeneration and defective neurotransmission in a C. elegans model of tauopathy. Proc Natl Acad Sci U S A 100(17):9980–9985

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Lakso M, Vartiainen S, Moilanen AM, Sirvio J, Thomas JH, Nass R, Blakely RD, Wong G (2003) Dopaminergic neuronal loss and motor deficits in C. elegans overexpressing human alpha-synuclein. J Neurochem 86(1):165–172

    Article  CAS  PubMed  Google Scholar 

  162. Wang J, Farr GW, Hall DH, Li F, Furtak K, Dreier L, Horwich AL (2009) An ALS-linked mutant SOD1 produces a locomotor defect associated with aggregation and synaptic dysfunction when expressed in neurons of C. elegans. PLoS Genet 5(1), e1000350

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  163. Moronetti Mazzeo LE, Dersh D, Boccitto M, Kalb RG, Lamitina T (2012) Stress and aging induce distinct polyQ protein aggregation states. Proc Natl Acad Sci U S A 109(26):10587–10592

    Article  PubMed  PubMed Central  Google Scholar 

  164. Knight AL, Yan X, Hamamichi S, Ajjuri RR, Mazzulli JR, Zhang MW, Daigle JG, Zhang S, Borom AR, Roberts LR, Lee SK, DeLeon SM, Viollet-Djelassi C, Krainc D, O’Donnell JM, Caldwell KA, Caldwell GA (2014) The glycolytic enzyme, GPI, is a functionally conserved modifier of dopaminergic neurodegeneration in Parkinson’s models. Cell Metab 20(1):145–157

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. Cohen E, Bieschke J, Perciavalle RM, Kelly JW, Dillin A (2006) Opposing activities protect against age-onset proteotoxicity. Science (New York, NY) 313(5793):1604–1610

    Article  CAS  Google Scholar 

  166. Florez-McClure ML, Hohsfield LA, Fonte G, Bealor MT, Link CD (2007) Decreased insulin-receptor signaling promotes the autophagic degradation of beta-amyloid peptide in C. elegans. Autophagy 3(6):569–580

    Article  CAS  PubMed  Google Scholar 

  167. Rosen DR, Siddique T, Patterson D, Figlewicz DA, Sapp P, Hentati A, Donaldson D, Goto J, O’Regan JP, Deng HX et al (1993) Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362(6415):59–62

    Article  CAS  PubMed  Google Scholar 

  168. Li J, Huang KX, Le WD (2013) Establishing a novel C. elegans model to investigate the role of autophagy in amyotrophic lateral sclerosis. Acta Pharmacol Sin 34(5):644–650

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. David DC, Ollikainen N, Trinidad JC, Cary MP, Burlingame AL, Kenyon C (2010) Widespread protein aggregation as an inherent part of aging in C. elegans. PLoS Biol 8(8), e1000450

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  170. Walther DM, Kasturi P, Zheng M, Pinkert S, Vecchi G, Ciryam P, Morimoto RI, Dobson CM, Vendruscolo M, Mann M, Hartl FU (2015) Widespread proteome remodeling and aggregation in aging C. elegans. Cell 161(4):919–932

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  171. Pan CL, Peng CY, Chen CH, McIntire S (2011) Genetic analysis of age-dependent defects of the C. elegans touch receptor neurons. Proc Natl Acad Sci U S A 108(22):9274–9279

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Tank EM, Rodgers KE, Kenyon C (2011) Spontaneous age-related neurite branching in C. elegans. J Neurosci 31(25):9279–9288

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. Kauffman AL, Ashraf JM, Corces-Zimmerman MR, Landis JN, Murphy CT (2010) Insulin signaling and dietary restriction differentially influence the decline of learning and memory with age. PLoS Biol 8(5), e1000372

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  174. Tazearslan C, Cho M, Suh Y (2012) Discovery of functional gene variants associated with human longevity: opportunities and challenges. J Gerontol Ser A Biol Sci Med Sci 67(4):376–383

    Article  CAS  Google Scholar 

Download references

Acknowledgments

We thank the members of Lee laboratory for critical comments on the manuscript. This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korean Government (MSIP) (NRF-2013R1A1A2014754) to S.-J.V.L.

Author information

Author notes

    Authors and Affiliations

    1. Pohang University of Science and Technology, Pohang, Gyeongbuk, South Korea

      Seon Woo A. An, Murat Artan, Sangsoon Park, Ozlem Altintas & Seung-Jae V. Lee

    Authors
    1. Seon Woo A. An
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Murat Artan
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Sangsoon Park
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Ozlem Altintas
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Seung-Jae V. Lee
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Seung-Jae V. Lee .

    Editor information

    Editors and Affiliations

    1. Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark

      Anders Olsen

    2. Department of Metabolics & Aging, The Scripps Research Institute - Scripps Florida, Jupiter, Florida, USA

      Matthew S. Gill

    Rights and permissions

    Reprints and permissions

    Copyright information

    © 2017 Springer International Publishing Switzerland

    About this chapter

    Cite this chapter

    An, S.W.A., Artan, M., Park, S., Altintas, O., Lee, SJ.V. (2017). Longevity Regulation by Insulin/IGF-1 Signalling. In: Olsen, A., Gill, M. (eds) Ageing: Lessons from C. elegans. Healthy Ageing and Longevity. Springer, Cham. https://doi.org/10.1007/978-3-319-44703-2_4

    Download citation

    Publish with us

    Policies and ethics

    Search

    Navigation