The role of insulin/IGF-1 signaling in the longevity of model invertebrates, C. elegans and D. melanogaster

BMB Reports

Volumn 49, Issue 2, 2016, Pages 81-92

  Altintas, Ozlem ^a   Park, Sangsoon ^a   Lee, Seung Jae V ^a  

^a Pohang University of Science and Technology (POSTECH)   (South Korea)

Author keywords

Aging; C. elegans; D. melanogaster; Insulin IGF 1 signaling; Longevity

Indexed keywords

INSULIN; SOMATOMEDIN C;

ANIMAL; CAENORHABDITIS ELEGANS; DROSOPHILA MELANOGASTER; LONGEVITY; METABOLISM; PHYSIOLOGY; SIGNAL TRANSDUCTION;

ANIMALS; CAENORHABDITIS ELEGANS; DROSOPHILA MELANOGASTER; INSULIN; INSULIN-LIKE GROWTH FACTOR I; LONGEVITY; SIGNAL TRANSDUCTION;

EID: 84960427629     PISSN: 19766696     EISSN: 1976670X     Source Type: Journal    
DOI: 10.5483/BMBRep.2016.49.2.261     Document Type: Article

References (207)

1. Lee Y, An S, Artan M, et al. (2015) Genes and Pathways That Influence Longevity in Caenorhabditis elegans; in Aging Mechanisms, Mori N and Mook-Jung I (eds), 123-169, Springer Japan
2. Giannakou ME and Partridge L (2007) Role of insulin-like signalling in Drosophila lifespan. Trends Biochem Sci 32, 180-188.
3. Fontana L, Partridge L and Longo VD (2010) Extending healthy life span--from yeast to humans. Science 328, 321-326.
4. Kenyon CJ (2010) The genetics of ageing. Nature 464, 504-512.
5. Morris JZ, Tissenbaum HA and Ruvkun G (1996) A phosphatidylinositol-3-OH kinase family member regulating longevity and diapause in Caenorhabditis elegans. Nature 382, 536-539.
6. Kimura KD, Tissenbaum HA, Liu Y and Ruvkun G (1997) daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans. Science 277, 942-946.
7. Friedman DB and Johnson TE (1988) A mutation in the age-1 gene in Caenorhabditis elegans lengthens life and reduces hermaphrodite fertility. Genetics 118, 75-86.
8. Kenyon C, Chang J, Gensch E, Rudner A and Tabtiang R (1993) A C. elegans mutant that lives twice as long as wild type. Nature 366, 461-464.
9. Klass MR (1983) A method for the isolation of longevity mutants in the nematode Caenorhabditis elegans and initial results. Mech Ageing Dev 22, 279-286.
10. Wolkow CA, Munoz MJ, Riddle DL and 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, 49591-49597.
11. Zhou K, Pandol S, Bokoch G and 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.
12. Ogg S and Ruvkun G (1998) The C. elegans PTEN homolog, DAF-18, acts in the insulin receptor-like metabolic signaling pathway. Mol Cell 2, 887-893.
13. Gil EB, Malone Link E, Liu LX, Johnson CD and Lees JA (1999) Regulation of the insulin-like developmental pathway of Caenorhabditis elegans by a homolog of the PTEN tumor suppressor gene. Proc Natl Acad Sci U S A 96, 2925-2930.
14. Mihaylova VT, Borland CZ, Manjarrez L, Stern MJ and Sun H (1999) The PTEN tumor suppressor homolog in Caenorhabditis elegans regulates longevity and dauer formation in an insulin receptor-like signaling pathway. Proc Natl Acad Sci U S A 96, 7427-7432.
15. Rouault JP, Kuwabara PE, Sinilnikova OM, Duret L, Thierry-Mieg D and Billaud M (1999) Regulation of dauer larva development in Caenorhabditis elegans by daf-18, a homologue of the tumour suppressor PTEN. Curr Biol 9, 329-332.
16. Dorman JB, Albinder B, Shroyer T and Kenyon C (1995) The age-1 and daf-2 genes function in a common pathway to control the lifespan of Caenorhabditis elegans. Genetics 141, 1399-1406.
17. Larsen PL, Albert PS and Riddle DL (1995) Genes that regulate both development and longevity in Caenorhabditis elegans. Genetics 139, 1567-1583.
18. Gottlieb S and Ruvkun G (1994) daf-2, daf-16 and daf-23: genetically interacting genes controlling Dauer formation in Caenorhabditis elegans. Genetics 137, 107-120.
19. Solari F, Bourbon-Piffaut A, Masse I, Payrastre B, Chan AM and Billaud M (2005) The human tumour suppressor PTEN regulates longevity and dauer formation in Caenorhabditis elegans. Oncogene 24, 20-27.
20. Paradis S, Ailion M, Toker A, Thomas JH and 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, 1438-1452.
21. Paradis S and 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, 2488-2498.
22. Hertweck M, Gobel C and 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, 577-588.
23. Chen AT, Guo C, Dumas KJ, Ashrafi K and Hu PJ (2013) Effects of Caenorhabditis elegans sgk-1 mutations on lifespan, stress resistance, and DAF-16/FoxO regulation. Aging Cell 12, 932-940.
24. Xiao R, Zhang B, Dong Y, et al. (2013) A genetic program promotes C. elegans longevity at cold temperatures via a thermosensitive TRP channel. Cell 152, 806-817.
25. Henderson ST and Johnson TE (2001) daf-16 integrates developmental and environmental inputs to mediate aging in the nematode Caenorhabditis elegans. Curr Biol 11, 1975-1980.
26. Lee RY, Hench J and 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, 1950-1957.
27. Lin K, Hsin H, Libina N and Kenyon C (2001) Regulation of the Caenorhabditis elegans longevity protein DAF-16. by insulin/IGF-1 and germline signaling. Nat Genet 28, 139-145.
28. Cahill CM, Tzivion G, Nasrin N, et al. (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, 13402-13410.
29. Ogg S, Paradis S, Gottlieb S, et al. (1997) The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans. Nature 389, 994-999.
30. Lin K, Dorman JB, Rodan A and Kenyon C (1997) daf-16: An HNF-3/forkhead family member that can function to double the life-span of Caenorhabditis elegans. Science 278, 1319-1322.
31. Oh SW, Mukhopadhyay A, Svrzikapa N, Jiang F, Davis RJ and 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, 4494-4499.
32. Curtis R, O'Connor G and DiStefano PS (2006) Aging networks in Caenorhabditis elegans: AMP-activated protein kinase (aak-2) links multiple aging and metabolism pathways. Aging Cell 5, 119-126.
33. Greer EL, Dowlatshahi D, Banko MR, et al. (2007) An AMPK-FOXO pathway mediates longevity induced by a novel method of dietary restriction in C. elegans. Curr Biol 17, 1646-1656.
34. Apfeld J, O'Connor G, McDonagh T, DiStefano PS and 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, 3004-3009.
35. Lehtinen MK, Yuan Z, Boag PR, et al. (2006) A conserved MST-FOXO signaling pathway mediates oxidative-stress responses and extends life span. Cell 125, 987-1001.
36. Wolff S, Ma H, Burch D, Maciel GA, Hunter T and Dillin A (2006) SMK-1, an essential regulator of DAF-16-mediated longevity. Cell 124, 1039-1053.
37. Seo M, Seo K, Hwang W, et al. (2015) RNA helicase HEL-1 promotes longevity by specifically activating DAF-16/FOXO transcription factor signaling in Caenorhabditis elegans. Proc Natl Acad Sci U S A 112, E4246-E4255.
38. Chiang WC, Tishkoff DX, Yang B, et al. (2012) C. elegans SIRT6/7 homolog SIR-2.4 promotes DAF-16 relocalization and function during stress. PLoS Genet 8, e1002948.
39. Hu PJ, Xu J and Ruvkun G (2006) Two membrane-associated tyrosine phosphatase homologs potentiate C. elegans AKT-1/PKB signaling. PLoS Genet 2, e99.
40. Li J, Ebata A, Dong Y, Rizki G, Iwata T and Lee SS (2008) Caenorhabditis elegans HCF-1 functions in longevity maintenance as a DAF-16 regulator. PLoS Biol 6, e233.
41. Alam H, Williams TW, Dumas KJ, et al. (2010) EAK-7. controls development and life span by regulating nuclear DAF-16/FoxO activity. Cell Metab 12, 30-41.
42. Berdichevsky A, Viswanathan M, Horvitz HR and Guarente L (2006) C. elegans SIR-2.1 interacts with 14-3-3. proteins to activate DAF-16 and extend life span. Cell 125, 1165-1177.
43. Li J, Tewari M, Vidal M and Lee SS (2007) The 14-3-3. protein FTT-2 regulates DAF-16 in Caenorhabditis elegans. Dev Biol 301, 82-91.
44. Wang Y, Oh SW, Deplancke B, Luo J, Walhout AJ and 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, 741-747.
45. Lee SS, Kennedy S, Tolonen AC and Ruvkun G (2003) DAF-16 target genes that control C. elegans life-span and metabolism. Science 300, 644-647.
46. Ookuma S, Fukuda M and Nishida E (2003) Identification of a DAF-16 transcriptional target gene, scl-1, that regulates longevity and stress resistance in Caenorhabditis elegans. Curr Biol 13, 427-431.
47. Murphy CT, McCarroll SA, Bargmann CI, et al. (2003) Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans. Nature 424, 277-283.
48. McElwee J, Bubb K and Thomas JH (2003) Transcriptional outputs of the Caenorhabditis elegans forkhead protein DAF-16. Aging Cell 2, 111-121.
49. Golden TR and Melov S (2004) Microarray analysis of gene expression with age in individual nematodes. Aging Cell 3, 111-124.
50. Halaschek-Wiener J, Khattra JS, McKay S, et al. (2005) Analysis of long-lived C. elegans daf-2 mutants using serial analysis of gene expression. Genome Res 15, 603-615.
51. Lee SJ, Murphy CT and Kenyon C (2009) Glucose shortens the life span of C. elegans by downregulating DAF-16/FOXO activity and aquaporin gene expression. Cell Metab 10, 379-391.
52. Tullet JM, Hertweck M, An JH, et al. (2008) Direct inhibition of the longevity-promoting factor SKN-1 by insulin-like signaling in C. elegans. Cell 132, 1025-1038.
53. An JH and Blackwell TK (2003) SKN-1 links C. elegans mesendodermal specification to a conserved oxidative stress response. Genes Dev 17, 1882-1893.
54. An JH, Vranas K, Lucke M, et al. (2005) Regulation of the Caenorhabditis elegans oxidative stress defense protein SKN-1 by glycogen synthase kinase-3. Proc Natl Acad Sci U S A 102, 16275-16280.
55. Kahn NW, Rea SL, Moyle S, Kell A and Johnson TE (2008) Proteasomal dysfunction activates the transcription factor SKN-1 and produces a selective oxidativestress response in Caenorhabditis elegans. Biochem J 409, 205-213.
56. Oliveira RP, Porter Abate J, Dilks K, et al. (2009) Condition-adapted stress and longevity gene regulation by Caenorhabditis elegans SKN-1/Nrf. Aging Cell 8, 524-541.
57. Wang J, Robida-Stubbs S, Tullet JM, Rual JF, Vidal M and Blackwell TK (2010) RNAi screening implicates a SKN-1-dependent transcriptional response in stress resistance and longevity deriving from translation inhibition. PLoS Genet 6, e1001048.
58. Staab TA, Griffen TC, Corcoran C, Evgrafov O, Knowles JA and Sieburth D (2013) The conserved SKN-1/Nrf2. stress response pathway regulates synaptic function in Caenorhabditis elegans. PLoS Genet 9, e1003354.
59. Glover-Cutter KM, Lin S and Blackwell TK (2013) Integration of the unfolded protein and oxidative stress responses through SKN-1/Nrf. PLoS Genet 9, e1003701.
60. Choe KP, Przybysz AJ and Strange K (2009) The WD40. repeat protein WDR-23 functions with the CUL4/DDB1. ubiquitin ligase to regulate nuclear abundance and activity of SKN-1 in Caenorhabditis elegans. Mol Cell Biol 29, 2704-2715.
61. Park SK, Tedesco PM and Johnson TE (2009) Oxidative stress and longevity in Caenorhabditis elegans as mediated by SKN-1. Aging Cell 8, 258-269.
62. Pang S, Lynn DA, Lo JY, Paek J and Curran SP (2014) SKN-1 and Nrf2 couples proline catabolism with lipid metabolism during nutrient deprivation. Nat Commun 5, 5048.
63. Kell A, Ventura N, Kahn N and Johnson TE (2007) Activation of SKN-1 by novel kinases in Caenorhabditis elegans. Free Radic Biol Med 43, 1560-1566.
64. Li X, Matilainen O, Jin C, Glover-Cutter KM, Holmberg CI and Blackwell TK (2011) Specific SKN-1/Nrf stress responses to perturbations in translation elongation and proteasome activity. PLoS Genet 7, e1002119.
65. Ewald CY, Landis JN, Porter Abate J, Murphy CT and Blackwell TK (2015) Dauer-independent insulin/IGF-1-signalling implicates collagen remodelling in longevity. Nature 519, 97-101.
66. Hsu AL, Murphy CT and Kenyon C (2003) Regulation of aging and age-related disease by DAF-16 and heat-shock factor. Science 300, 1142-1145.
67. Morley JF and Morimoto RI (2004) Regulation of longevity in Caenorhabditis elegans by heat shock factor and molecular chaperones. Mol Biol Cell 15, 657-664.
68. Cohen E, Bieschke J, Perciavalle RM, Kelly JW and Dillin A (2006) Opposing activities protect against age-onset proteotoxicity. Science 313, 1604-1610.
69. Chiang WC, Ching TT, Lee HC, Mousigian C and Hsu AL (2012) HSF-1 regulators DDL-1/2 link insulin-like signaling to heat-shock responses and modulation of longevity. Cell 148, 322-334.
70. Seo K, Choi E, Lee D, Jeong DE, Jang SK and 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, 1073-1081.
71. Garigan D, Hsu AL, Fraser AG, Kamath RS, Ahringer J and Kenyon C (2002) Genetic analysis of tissue aging in Caenorhabditis elegans: a role for heat-shock factor and bacterial proliferation. Genetics 161, 1101-1112.
72. Douglas PM, Baird NA, Simic MS, et al. (2015) Heterotypic signals from neural HSF-1 separate thermotolerance from longevity. Cell Rep 12, 1196-1204.
73. Baird NA, Douglas PM, Simic MS, et al. (2014) HSF-1-mediated cytoskeletal integrity determines thermotolerance and life span. Science 346, 360-363.
74. Amin J, Ananthan J and Voellmy R (1988) Key features of heat shock regulatory elements. Mol Cell Biol 8, 3761-3769.
75. Kay RJ, Boissy RJ, Russnak RH and Candido EP (1986) Efficient transcription of a Caenorhabditis elegans heat shock gene pair in mouse fibroblasts is dependent on multiple promoter elements which can function bidirectionally. Mol Cell Biol 6, 3134-3143.
76. Russnak RH and Candido EP (1985) Locus encoding a family of small heat shock genes in Caenorhabditis elegans: two genes duplicated to form a 3.8-kilobase inverted repeat. Mol Cell Biol 5, 1268-1278.
77. Yokoyama K, Fukumoto K, Murakami T, et al. (2002) Extended longevity of Caenorhabditis elegans by knocking in extra copies of hsp70F, a homolog of mot-2. (mortalin)/mthsp70/Grp75. FEBS Lett 516, 53-57.
78. Walker GA and Lithgow GJ (2003) Lifespan extension in C. elegans by a molecular chaperone dependent upon insulin-like signals. Aging Cell 2, 131-139.
79. Pierce SB, Costa M, Wisotzkey R, et al. (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, 672-686.
80. Li W, Kennedy SG and 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, 844-858.
81. Chen Z, Hendricks M, Cornils A, Maier W, Alcedo J and Zhang Y (2013) Two insulin-like peptides antagonistically regulate aversive olfactory learning in C. elegans. Neuron 77, 572-585.
82. Cornils A, Gloeck M, Chen Z, Zhang Y and Alcedo J (2011) Specific insulin-like peptides encode sensory information to regulate distinct developmental processes. Development 138, 1183-1193.
83. Murphy CT, Lee SJ and 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, 19046-19050.
84. Kawli T and Tan MW (2008) Neuroendocrine signals modulate the innate immunity of Caenorhabditis elegans through insulin signaling. Nat Immunol 9, 1415-1424.
85. Malone EA, Inoue T and Thomas JH (1996) Genetic analysis of the roles of daf-28 and age-1 in regulating Caenorhabditis elegans dauer formation. Genetics 143, 1193-1205.
86. Malone EA and Thomas JH (1994) A screen for nonconditional dauer-constitutive mutations in Caenorhabditis elegans. Genetics 136, 879-886.
87. Fernandes de Abreu DA, Caballero A, Fardel P, et al. (2014) An insulin-to-insulin regulatory network orchestrates phenotypic specificity in development and physiology. PLoS Genet 10, e1004225.
88. Ritter AD, Shen Y, Fuxman Bass J, et al. (2013) Complex expression dynamics and robustness in C. elegans insulin networks. Genome Res 23, 954-965.
89. Hung WL, Wang Y, Chitturi J and Zhen M (2014) A Caenorhabditis elegans developmental decision requires insulin signaling-mediated neuron-intestine communication. Development 141, 1767-1779.
90. Chen Y and Baugh LR (2014) Ins-4 and daf-28 function redundantly to regulate C. elegans L1 arrest. Dev Biol 394, 314-326.
91. Duret L, Guex N, Peitsch MC and Bairoch A (1998) New insulin-like proteins with atypical disulfide bond pattern characterized in Caenorhabditis elegans by comparative sequence analysis and homology modeling. Genome Res 8, 348-353.
92. Michaelson D, Korta DZ, Capua Y and Hubbard EJ (2010) Insulin signaling promotes germline proliferation in C. elegans. Development 137, 671-680.
93. Leinwand SG and Chalasani SH (2013) Neuropeptide signaling remodels chemosensory circuit composition in Caenorhabditis elegans. Nat Neurosci 16, 1461-1467.
94. Ohta A, Ujisawa T, Sonoda S and Kuhara A (2014) Light and pheromone-sensing neurons regulates cold habituation through insulin signalling in Caenorhabditis elegans. Nat Commun 5, 4412.
95. Wolkow CA, Kimura KD, Lee MS and Ruvkun G (2000) Regulation of C. elegans life-span by insulinlike signaling in the nervous system. Science 290, 147-150.
96. Iser WB, Gami MS and Wolkow CA (2007) Insulin signaling in Caenorhabditis elegans regulates both endocrine-like and cell-autonomous outputs. Dev Biol 303, 434-447.
97. Hu PJ (2007) Dauer. WormBook: the online review of C. elegans biology, 1-19.
98. Riddle DL and Albert PS (1997) Genetic and Environmental Regulation of Dauer Larva Development; in C. elegans II, Riddle DL, Blumenthal T, Meyer BJ, et al. (eds), Cold Spring Harbor Laboratory Press, Cold Spring Harbor (NY)
99. Libina N, Berman JR and Kenyon C (2003) Tissue-specific activities of C. elegans DAF-16 in the regulation of lifespan. Cell 115, 489-502.
100. Dillin A, Crawford DK and Kenyon C (2002) Timing requirements for insulin/IGF-1 signaling in C. elegans. Science 298, 830-834.
101. Larsen PL (1993) Aging and resistance to oxidative damage in Caenorhabditis elegans. Proc Natl Acad Sci U S A 90, 8905-8909.
102. Vanfleteren JR (1993) Oxidative stress and ageing in Caenorhabditis elegans. Biochem J 292 (Pt 2), 605-608.
103. Honda Y and 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, 1385-1393.
104. Gems D, Sutton AJ, Sundermeyer ML, et al. (1998) Two pleiotropic classes of daf-2 mutation affect larval arrest, adult behavior, reproduction and longevity in Caenorhabditis elegans. Genetics 150, 129-155.
105. Lithgow GJ, White TM, Melov S and Johnson TE (1995) Thermotolerance and extended life-span conferred by single-gene mutations and induced by thermal stress. Proc Natl Acad Sci U S A 92, 7540-7544.
106. McColl G, Rogers AN, Alavez S, et al. (2010) Insulin-like signaling determines survival during stress via posttranscriptional mechanisms in C. elegans. Cell Metab 12, 260-272.
107. Scott BA, Avidan MS and Crowder CM (2002) Regulation of hypoxic death in C. elegans by the insulin/IGF receptor homolog DAF-2. Science 296, 2388-2391.
108. Mabon ME, Scott BA and Crowder CM (2009) Divergent mechanisms controlling hypoxic sensitivity and lifespan by the DAF-2/insulin/IGF-receptor pathway. PLoS One 4, e7937.
109. Lamitina ST and Strange K (2005) Transcriptional targets of DAF-16 insulin signaling pathway protect C. elegans from extreme hypertonic stress. Am J Physiol Cell Physiol 288, C467-C474.
110. Burkewitz K, Choe K and Strange K (2011) Hypertonic stress induces rapid and widespread protein damage in C. elegans. Am J Physiol Cell Physiol 301, C566-C576.
111. Murakami S and Johnson TE (1996) A genetic pathway conferring life extension and resistance to UV stress in Caenorhabditis elegans. Genetics 143, 1207-1218.
112. Barsyte D, Lovejoy DA and Lithgow GJ (2001) Longevity and heavy metal resistance in daf-2 and age-1 long-lived mutants of Caenorhabditis elegans. FASEB J 15, 627-634.
113. Morley JF, Brignull HR, Weyers JJ and 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, 10417-10422.
114. Henis-Korenblit S, Zhang PC, Hansen M, et al. (2010) Insulin/IGF-1 signaling mutants reprogram ER stress response regulators to promote longevity. Proc Natl Acad Sci U S A 107, 9730-9735.
115. Essers MA, de Vries-Smits LM, Barker N, Polderman PE, Burgering BM and Korswagen HC (2005) Functional interaction between beta-catenin and FOXO in oxidative stress signaling. Science 308, 1181-1184.
116. Mueller MM, Castells-Roca L, Babu V, et al. (2014) DAF-16/FOXO and EGL-27/GATA promote developmental growth in response to persistent somatic DNA damage. Nat Cell Biol 16, 1168-1179.
117. Ermolaeva MA and Schumacher B (2014) Insights from the worm: the C. elegans model for innate immunity. Semin Immunol 26, 303-309.
118. Garsin DA, Villanueva JM, Begun J, et al. (2003) Long-lived C. elegans daf-2 mutants are resistant to bacterial pathogens. Science 300, 1921.
119. Kerry S, TeKippe M, Gaddis NC and Aballay A (2006) GATA transcription factor required for immunity to bacterial and fungal pathogens. PLoS One 1, e77.
120. Singh V and Aballay A (2006) Heat-shock transcription factor (HSF)-1 pathway required for Caenorhabditis elegans immunity. Proc Natl Acad Sci U S A 103, 13092-13097.
121. Papp D, Csermely P and Soti C (2012) A role for SKN-1/Nrf in pathogen resistance and immunosenescence in Caenorhabditis elegans. PLoS Pathog 8, e1002673.
122. Evans EA, Chen WC and Tan MW (2008) The DAF-2 insulin-like signaling pathway independently regulates aging and immunity in C. elegans. Aging Cell 7, 879-893.
123. Portal-Celhay C, Bradley ER and Blaser MJ (2012) Control of intestinal bacterial proliferation in regulation of lifespan in Caenorhabditis elegans. BMC Micobiol 12, 49.
124. Evans EA, Kawli T and Tan M-W (2008) Pseudomonas aeruginosa suppresses host immunity by activating the DAF-2 insulin-like signaling pathway in Caenorhabditis elegans. PLoS Pathog 4, e1000175.
125. Link CD (1995) Expression of human β-amyloid peptide in transgenic Caenorhabditis elegans. Proc Natl Acad Sci U S A 92, 9368-9372.
126. Fay DS, Fluet A, Johnson CJ and Link CD (1998) In Vivo Aggregation of β-Amyloid Peptide Variants. J Neurochem 71, 1616-1625.
127. Link CD, Taft A, Kapulkin V, et al. (2003) Gene expression analysis in a transgenic Caenorhabditis elegans Alzheimer's disease model. Neurobiol Aging 24, 397-413.
128. Faber PW, Alter JR, MacDonald ME and Hart AC (1999) Polyglutamine-mediated dysfunction and apoptotic death of a Caenorhabditis elegans sensory neuron. Proc Natl Acad Sci U S A 96, 179-184.
129. Satyal SH, Schmidt E, Kitagawa K, et al. (2000) Polyglutamine aggregates alter protein folding homeostasis in Caenorhabditis elegans. Proc Natl Acad Sci U S A 97, 5750-5755.
130. Parker JA, Connolly JB, Wellington C, Hayden M, Dausset J and Neri C (2001) Expanded polyglutamines in Caenorhabditis elegans cause axonal abnormalities and severe dysfunction of PLM mechanosensory neurons without cell death. Proc Natl Acad Sci U S A 98, 13318-13323.
131. Brignull HR, Moore FE, Tang SJ and Morimoto RI (2006) Polyglutamine proteins at the pathogenic threshold display neuron-specific aggregation in a pan-neuronal Caenorhabditis elegans model. J Neurosci 26, 7597-7606.
132. Mohri-Shiomi A and Garsin DA (2008) Insulin signaling and the heat shock response modulate protein homeostasis in the Caenorhabditis elegans intestine during infection. J Biol Chem 283, 194-201.
133. Lakso M, Vartiainen S, Moilanen AM, et al. (2003) Dopaminergic neuronal loss and motor deficits in Caenorhabditis elegans overexpressing human alpha-synuclein. J Neurochem 86, 165-172.
134. Cao S, Gelwix CC, Caldwell KA and Caldwell GA (2005) Torsin-mediated protection from cellular stress in the dopaminergic neurons of Caenorhabditis elegans. J Neurosci 25, 3801-3812.
135. Kuwahara T, Koyama A, Gengyo-Ando K, et al. (2006) Familial Parkinson mutant α-synuclein causes dopamine neuron dysfunction in transgenic Caenorhabditis elegans. J Biol Chem 281, 334-340.
136. Kuwahara T, Koyama A, Koyama S, et al. (2008) A systematic RNAi screen reveals involvement of endocytic pathway in neuronal dysfunction in α-synuclein transgenic C. elegans. Hum Mol Genet 17, 2997-3009.
137. Hamamichi S, Rivas RN, Knight AL, Cao S, Caldwell KA and Caldwell GA (2008) Hypothesis-based RNAi screening identifies neuroprotective genes in a Parkinson's disease model. Proc Natl Acad Sci U S A 105, 728-733.
138. Oeda T, Shimohama S, Kitagawa N, et al. (2001) Oxidative stress causes abnormal accumulation of familial amyotrophic lateral sclerosis-related mutant SOD1 in transgenic Caenorhabditis elegans. Hum Mol Genet 10, 2013-2023.
139. Gidalevitz T, Krupinski T, Garcia S and Morimoto RI (2009) Destabilizing protein polymorphisms in the genetic background direct phenotypic expression of mutant SOD1 toxicity. PLoS Genet 5, e1000399.
140. Wang J, Farr GW, Hall DH, et al. (2009) An ALS-linked mutant SOD1 produces a locomotor defect associated with aggregation and synaptic dysfunction when expressed in neurons of Caenorhabditis elegans. PLoS Genet 5, e1000350.
141. Li J, Huang KX and Le WD (2013) Establishing a novel C. elegans model to investigate the role of autophagy in amyotrophic lateral sclerosis. Acta Pharmacol Sin 34, 644-650.
142. Florez-McClure ML, Hohsfield LA, Fonte G, Bealor MT and Link CD (2007) Decreased insulin-receptor signaling promotes the autophagic degradation of β-amyloid peptide in C. elegans. Autophagy 3, 569-580.
143. David DC, Ollikainen N, Trinidad JC, Cary MP, Burlingame AL and Kenyon C (2010) Widespread protein aggregation as an inherent part of aging in C. elegans. PLoS Biol 8, e1000450.
144. Wang H, Lim PJ, Yin C, Rieckher M, Vogel BE and Monteiro MJ (2006) Suppression of polyglutamine-induced toxicity in cell and animal models of Huntington's disease by ubiquilin. Hum Mol Genet 15, 1025-1041.
145. Wang H, Lim PJ, Karbowski M and Monteiro MJ (2009) Effects of overexpression of huntingtin proteins on mitochondrial integrity. Hum Mol Genet 18, 737-752.
146. Steinkraus KA, Smith ED, Davis C, et al. (2008) Dietary restriction suppresses proteotoxicity and enhances longevity by an hsf-1-dependent mechanism in Caenorhabditis elegans. Aging Cell 7, 394-404.
147. Faber PW, Voisine C, King DC, Bates EA and Hart AC (2002) Glutamine/proline-rich PQE-1 proteins protect Caenorhabditis elegans neurons from huntingtin polyglutamine neurotoxicity. Proc Natl Acad Sci U S A 99, 17131-17136.
148. Parker JA, Metzler M, Georgiou J, et al. (2007) Huntingtininteracting protein 1 influences worm and mouse presynaptic function and protects Caenorhabditis elegans neurons against mutant polyglutamine toxicity. J Neurosci 27, 11056-11064.
149. Parker JA, Arango M, Abderrahmane S, et al. (2005) Resveratrol rescues mutant polyglutamine cytotoxicity in nematode and mammalian neurons. Nat Genet 37, 349-350.
150. Bates EA, Victor M, Jones AK, Shi Y and Hart AC (2006) Differential contributions of Caenorhabditis elegans histone deacetylases to huntingtin polyglutamine toxicity. J Neurosci 26, 2830-2838.
151. Schapira AH and Jenner P (2011) Etiology and pathogenesis of Parkinson's disease. Mov Disord 26, 1049-1055.
152. Knight AL, Yan X, Hamamichi S, et al. (2014) The glycolytic enzyme, GPI, is a functionally conserved modifier of dopaminergic neurodegeneration in Parkinson's models. Cell Metab 20, 145-157.
153. Pasinelli P and Brown RH (2006) Molecular biology of amyotrophic lateral sclerosis: insights from genetics. Nat Rev Neurosci 7, 710-723.
154. Rosen DR, Siddique T, Patterson D, et al. (1993) Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362, 59-62.
155. Cudkowicz M, McKenna-Yasek D, Sapp P, et al. (1997) Epidemiology of mutations in superoxide dismutase in amyotrophic lateal sclerosis. Ann Neurol 41, 210-221.
156. Bohni R, Riesgo-Escovar J, Oldham S, et al. (1999) Autonomous control of cell and organ size by CHICO, a Drosophila homolog of vertebrate IRS1-4. Cell 97, 865-875.
157. Verdu J, Buratovich MA, Wilder EL and Birnbaum MJ (1999) Cell-autonomous regulation of cell and organ growth in Drosophila by Akt/PKB. Nat Cell Biol 1, 500-506.
158. Weinkove D, Neufeld TP, Twardzik T, Waterfield MD and Leevers SJ (1999) Regulation of imaginal disc cell size, cell number and organ size by Drosophila class I(A) phosphoinositide 3-kinase and its adaptor. Curr Biol 9, 1019-1029.
159. Leevers SJ, Weinkove D, MacDougall LK, Hafen E and Waterfield MD (1996) The Drosophila phosphoinositide 3-kinase Dp110 promotes cell growth. EMBO J 15, 6584-6594.
160. Junger MA, Rintelen F, Stocker H, et al. (2003) The Drosophila forkhead transcription factor FOXO mediates the reduction in cell number associated with reduced insulin signaling. J Biol 2, 20.
161. Kramer JM, Davidge JT, Lockyer JM and Staveley BE (2003) Expression of Drosophila FOXO regulates growth and can phenocopy starvation. BMC Dev Biol 3, 5.
162. Puig O, Marr MT, Ruhf ML and Tjian R (2003) Control of cell number by Drosophila FOXO: downstream and feedback regulation of the insulin receptor pathway. Genes Dev 17, 2006-2020.
163. Staveley BE, Ruel L, Jin J, et al. (1998) Genetic analysis of protein kinase B (AKT) in Drosophila. Curr Biol 8, 599-602.
164. Poltilove RM, Jacobs AR, Haft CR, Xu P and Taylor SI (2000) Characterization of Drosophila insulin receptor substrate. J Biol Chem 275, 23346-23354.
165. Petruzzelli L, Herrera R, Arenas-Garcia R, Fernandez R, Birnbaum MJ and Rosen OM (1986) Isolation of a Drosophila genomic sequence homologous to the kinase domain of the human insulin receptor and detection of the phosphorylated Drosophila receptor with an anti-peptide antibody. Proc Natl Acad Sci U S A 83, 4710-4714.
166. Fernandez-Almonacid R and Rosen OM (1987) Structure and ligand specificity of the Drosophila melanogaster insulin receptor. Mol Cell Biol 7, 2718-2727.
167. Fernandez R, Tabarini D, Azpiazu N, Frasch M and Schlessinger J (1995) The Drosophila insulin receptor homolog: a gene essential for embryonic development encodes two receptor isoforms with different signaling potential. EMBO J 14, 3373-3384.
168. Marin-Hincapie M and Garofalo RS (1999) The carboxyl terminal extension of the Drosophila insulin receptor homologue binds IRS-1 and influences cell survival. J Biol Chem 274, 24987-24994.
169. Franke TF, Tartof KD and Tsichlis PN (1994) The SH2-like Akt homology (AH) domain of c-akt is present in multiple copies in the genome of vertebrate and invertebrate eucaryotes. Cloning and characterization of the Drosophila melanogaster c-akt homolog Dakt1. Oncogene 9, 141-148.
170. Cho KS, Lee JH, Kim S, et al. (2001) Drosophila phosphoinositide-dependent kinase-1 regulates apoptosis and growth via the phosphoinositide 3-kinase-dependent signaling pathway. Proc Natl Acad Sci U S A 98, 6144-6149.
171. Linassier C, MacDougall LK, Domin J and Waterfield MD (1997) Molecular cloning and biochemical characterization of a Drosophila phosphatidylinositol-specific phosphoinositide 3-kinase. Biochem J 321 (Pt 3), 849-856.
172. Brogiolo W, Stocker H, Ikeya T, Rintelen F, Fernandez R and Hafen E (2001) An evolutionarily conserved function of the Drosophila insulin receptor and insulin-like peptides in growth control. Curr Biol 11, 213-221.
173. Gao X, Neufeld TP and Pan D (2000) Drosophila PTEN regulates cell growth and proliferation through PI3K-dependent and -independent pathways. Dev Biol 221, 404-418.
174. Goberdhan DC, Paricio N, Goodman EC, Mlodzik M and Wilson C (1999) Drosophila tumor suppressor PTEN controls cell size and number by antagonizing the Chico/PI3-kinase signaling pathway. Genes Dev 13, 3244-3258.
175. Huang H, Potter CJ, Tao W, et al. (1999) PTEN affects cell size, cell proliferation and apoptosis during Drosophila eye development. Development 126, 5365-5372.
176. Bai H, Kang P, Hernandez AM and Tatar M (2013) Activin signaling targeted by insulin/dFOXO regulates aging and muscle proteostasis in Drosophila. PLoS Genet 9, e1003941.
177. Hwangbo DS, Gershman B, Tu MP, Palmer M and Tatar M (2004) Drosophila dFOXO controls lifespan and regulates insulin signalling in brain and fat body. Nature 429, 562-566.
178. Gronke S, Clarke DF, Broughton S, Andrews TD and Partridge L (2010) Molecular evolution and functional characterization of Drosophila insulin-like peptides. PLoS Genet 6, e1000857.
179. Broughton SJ, Piper MD, Ikeya T, et al. (2005) Longer lifespan, altered metabolism, and stress resistance in Drosophila from ablation of cells making insulin-like ligands. Proc Natl Acad Sci U S A 102, 3105-3110.
180. Tatar M, Kopelman A, Epstein D, Tu MP, Yin CM and Garofalo RS (2001) A mutant Drosophila insulin receptor homolog that extends life-span and impairs neuroendocrine function. Science 292, 107-110.
181. Clancy DJ, Gems D, Harshman LG, et al. (2001) Extension of life-span by loss of CHICO, a Drosophila insulin receptor substrate protein. Science 292, 104-106.
182. Tu MP, Epstein D and Tatar M (2002) The demography of slow aging in male and female Drosophila mutant for the insulin-receptor substrate homologue chico. Aging Cell 1, 75-80.
183. Nielsen MD, Luo X, Biteau B, Syverson K and Jasper H (2008) 14-3-3ε antagonizes FoxO to control growth, apoptosis and longevity in Drosophila. Aging Cell 7, 688-699.
184. Demontis F and Perrimon N (2010) FOXO/4E-BP signaling in Drosophila muscles regulates organism-wide proteostasis during aging. Cell 143, 813-825.
185. Giannakou ME, Goss M, Junger MA, Hafen E, Leevers SJ and Partridge L (2004) Long-lived Drosophila with overexpressed dFOXO in adult fat body. Science 305, 361.
186. Wessells RJ, Fitzgerald E, Cypser JR, Tatar M and Bodmer R (2004) Insulin regulation of heart function in aging fruit flies. Nat Genet 36, 1275-1281.
187. Ford D, Hoe N, Landis GN, et al. (2007) Alteration of Drosophila life span using conditional, tissue-specific expression of transgenes triggered by doxycyline or RU486/Mifepristone. Exp Gerontol 42, 483-497.
188. Broeck JV (2001) Neuropeptides and their precursors in the fruitfly, Drosophila melanogaster. Peptides 22, 241-254.
189. Colombani J, Andersen DS and Léopold P (2012) Secreted peptide Dilp8 coordinates Drosophila tissue growth with developmental timing. Science 336, 582-585.
190. Garelli A, Gontijo AM, Miguela V, Caparros E and Dominguez M (2012) Imaginal discs secrete insulin-like peptide 8 to mediate plasticity of growth and maturation. Science 336, 579-582.
191. Cao C and Brown MR (2001) Localization of an insulin-like peptide in brains of two flies. Cell Tissue Res 304, 317-321.
192. Ikeya T, Galic M, Belawat P, Nairz K and Hafen E (2002) Nutrient-dependent expression of insulin-like peptides from neuroendocrine cells in the CNS contributes to growth regulation in Drosophila. Curr Biol 12, 1293-1300.
193. Rulifson EJ, Kim SK and Nusse R (2002) Ablation of insulin-producing neurons in flies: growth and diabetic phenotypes. Science 296, 1118-1120.
194. Lee KS, Kwon OY, Lee JH, et al. (2008) Drosophila short neuropeptide F signalling regulates growth by ERK-mediated insulin signalling. Nat Cell Biol 10, 468-475.
195. Grönke S and Partridge L (2010) The functions of insulin-like peptides in insects; in IGFs: Local Repair and Survival Factors Throughout Life Span, Clemmons DR, Robinson I and Christen Y (eds), 105-124, Springer
196. Nassel DR, Liu Y and Luo J (2015) Insulin/IGF signaling and its regulation in Drosophila. Gen Comp Endocrinol 221, 255-266.
197. Haselton A, Sharmin E, Schrader J, Sah M, Poon P and Fridell Y-WC (2010) Partial ablation of adult Drosophila insulin-producing neurons modulates glucose homeostasis and extends life span without insulin resistance. Cell Cycle 9, 3135-3143.
198. Jeong DE, Artan M, Seo K and Lee SJ (2012) Regulation of lifespan by chemosensory and thermosensory systems: findings in invertebrates and their implications in mammalian aging. Front Genet 3, 218.
199. Wang MC, Bohmann D and Jasper H (2005) JNK extends life span and limits growth by antagonizing cellular and organism-wide responses to insulin signaling. Cell 121, 115-125.
200. Bauer JH, Chang C, Morris SNS, et al. (2007) Expression of dominant-negative Dmp53 in the adult fly brain inhibits insulin signaling. Proc Natl Acad Sci U S A 104, 13355-13360.
201. Broughton S, Alic N, Slack C, et al. (2008) Reduction of DILP2 in Drosophila triages a metabolic phenotype from lifespan revealing redundancy and compensation among DILPs. PLoS One 3, e3721.
202. Okamoto N, Yamanaka N, Yagi Y, et al. (2009) A fat body-derived IGF-like peptide regulates postfeeding growth in Drosophila. Dev Cell 17, 885-891.
203. Slaidina M, Delanoue R, Gronke S, Partridge L and Léopold P (2009) A Drosophila insulin-like peptide promotes growth during nonfeeding states. Dev Cell 17, 874-884.
204. Bai H, Kang P and Tatar M (2012) Drosophila insulin-like peptide-6 (dilp6) expression from fat body extends lifespan and represses secretion of Drosophila insulin-like peptide-2 from the brain. Aging cell 11, 978-985.
205. Holzenberger M, Dupont J, Ducos B, et al. (2003) IGF-1. receptor regulates lifespan and resistance to oxidative stress in mice. Nature 421, 182-187.
206. Yuan R, Tsaih SW, Petkova SB, et al. (2009) Aging in inbred strains of mice: study design and interim report on median lifespans and circulating IGF1 levels. Aging Cell 8, 277-287.
207. Tazearslan C, Cho M and Suh Y (2012) Discovery of functional gene variants associated with human longevity: opportunities and challenges. J Gerontol A Biol Sci Med Sci 67, 376-383.