Younger for longer: Insulin signalling, immunity and ageing

Current Aging Science

Volumn 3, Issue 3, 2010, Pages 166-176

  Amrit, Francis R G ^a   May, Robin C ^a  

^a UNIVERSITY OF BIRMINGHAM   (United Kingdom)

Author keywords

Ageing; C. elegans; Daf 16; Insulin signalling

Indexed keywords

FREE RADICAL; INSULIN; REACTIVE OXYGEN METABOLITE; SOMATOMEDIN; TRANSCRIPTION FACTOR DAF 16;

AGING; ARTICLE; CAENORHABDITIS; CAENORHABDITIS ELEGANS; DROSOPHILA MELANOGASTER; GENETIC VARIABILITY; IMMUNITY; LIFESPAN; LIFESTYLE; LONGEVITY; MOUSE; NONHUMAN; PRIORITY JOURNAL; REGULATORY MECHANISM; SIGNAL TRANSDUCTION; STRESS;

AGING; ANIMALS; BIOLOGICAL EVOLUTION; HUMANS; IMMUNITY; PHOSPHATIDYLINOSITOL 3-KINASES; PHYLOGENY; SIGNAL TRANSDUCTION; SOMATOMEDINS;

EID: 78651278007     PISSN: 18746098     EISSN: 18746128     Source Type: Journal    
DOI: 10.2174/1874609811003030166     Document Type: Article

References (148)

1. Ropes JW, Murawski SA. Maximum shell length and longevity inocean quahogs, Arctica islandica Linne. ICES 1983; K: 32.
2. Metchnikoff E, Mitchell PC. The prolongation of life: optimisticstudies. New York & London: G. P. Putnam's sons 1908.
3. Guttman C. Older Americans 2000. New data system that trackshealth and well-being finds successes and disparities. Geriatrics 2000; 55: 63-6, 9.
4. Kornfeld K, Evason K. Effects of anticonvulsant drugs on life span. Arch Neurol 2006; 63: 491-6.
5. de Magalhaes JP, Budovsky A, Lehmann G, Costa J, Li Y, Fraifeld V, et al. The human ageing genomic resources: online databasesand tools for biogerontologists. Aging Cell 2009; 8: 65-72.
6. Kenyon C, Chang J, Gensch E, Rudner A, Tabtiang R. A C. elegans mutant that lives twice as long as wild type. Nature 1993; 366: 461-4.
7. Clancy DJ, Gems D, Harshman LG, Oldham S, Stocker H, Hafen E, et al. Extension of life-span by loss of CHICO, a Drosophilainsulin receptor substrate protein. Science 2001; 292: 104-6.
8. Weismann A. Ueber die Dauer des Lebens, ein Vortrag. Jena: G. Fischer 1882.
9. Medawar PB. An unsolved problem of biology. London: H. K. Lewis 1952; p. 24.
10. Williams GC. Pleiotropy, natural selection, and the evolution ofsenescence. Sci Aging Knowl Environ 2001; 2001: 13.
11. Harman D. Aging: a theory based on free radical and radiationchemistry. J Gerontol 1956; 11: 298-300.
12. Beckman KB, Ames BN. The free radical theory of aging matures. Physiol Rev 1998; 78: 547-81.
13. Pearl R. The Rate of Living. London: University of London Press 1928.
14. Klass MR. Aging in the nematode Caenorhabditis elegans: majorbiological and environmental factors influencing life span. MechAgeing Dev 1977; 6: 413-29.
15. Van Raamsdonk JM, Hekimi S. Deletion of the mitochondrialsuperoxide dismutase sod-2 extends lifespan in Caenorhabditiselegans. PLoS Genet 2009; 5: e1000361.
16. Wawryn J, Krzepilko A, Myszka A, Bilinski T. Deficiency insuperoxide dismutases shortens life span of yeast cells. ActaBiochim Pol 1999; 46: 249-53.
17. Kirby K, Hu J, Hilliker AJ, Phillips JP. RNA interference-mediatedsilencing of Sod2 in Drosophila leads to early adult-onset mortalityand elevated endogenous oxidative stress. Proc Natl Acad Sci USA 2002; 99: 16162-7.
18. Phillips JP, Campbell SD, Michaud D, Charbonneau M, Hilliker AJ. Null mutation of copper-zinc superoxide-dismutase indrosophila confers hypersensitivity to paraquat and reducedlongevity. Proc Natl Acad Sci USA 1989; 86: 2761-5.
19. Lebovitz RM, Zhang H, Vogel H, Cartwright J, Jr., Dionne L, Lu N, et al. Neurodegeneration, myocardial injury, and perinatal deathin mitochondrial superoxide dismutase-deficient mice. Proc NatlAcad Sci USA 1996; 93: 9782-7.
20. Li Y, Huang TT, Carlson EJ, Melov S, Ursell PC, Olson JL, et al. Dilated cardiomyopathy and neonatal lethality in mutant micelacking manganese superoxide dismutase. Nat Genet 1995; 11: 376-81.
21. Gems D, Doonan R. Antioxidant defense and aging in C. elegans:is the oxidative damage theory of aging wrong? Cell Cycle 2009; 8: 1681-7.
22. Morin GB. Telomere control of replicative lifespan. Exp Gerontol 1997; 32: 375-82.
23. Hayflick L. The limited in vitro lifetime of human diploid cellstrains. Exp Cell Res 1965; 37: 614-36.
24. Sitte N, Saretzki G, von Zglinicki T. Accelerated telomereshortening in fibroblasts after extended periods of confluency. FreeRadic Biol Med 1998; 24: 885-93.
25. Guachalla LM, Ju Z, Koziel R, von Figura G, Song Z, Fusser M, et al. Sod2 haploinsufficiency does not accelerate aging of telomeredysfunctional mice. Aging (Albany NY) 2009; 1: 303-15.
26. Bodnar AG, Ouellette M, Frolkis M, Holt SE, Chiu C-P, Morin GB, et al. Extension of life-span by introduction of telomerase intonormal human cells. Science 1998; 279: 349-52.
27. Joeng KS, Song EJ, Lee KJ, Lee J. Long lifespan in worms withlong telomeric DNA. Nat Genet 2004; 36: 607-11.
28. Kurz CL, Shapira M, Chen K, Baillie DL, Tan M-W. Caenorhabditis elegans pgp-5 is involved in resistance to bacterialinfection and heavy metal and its regulation requires TIR-1 and ap38 map kinase cascade. Biochem Biophys Res Commun 2007; 363: 438-43.
29. Houthoofd K, Braeckman BP, Johnson TE, Vanfleteren JR. Lifeextension via dietary restriction is independent of the Ins/IGF-1signalling pathway in Caenorhabditis elegans. Exp Gerontol 2003; 38: 947-54.
30. Ewbank JJ. Tackling both sides of the host-pathogen equation withCaenorhabditis elegans. Microbes Infect 2002; 4: 247-56.
31. Baldi C, Cho S, Ellis RE. Mutations in two independent pathwaysare sufficient to create hermaphroditic nematodes. Science 2009; 326: 1002-5.
32. Wood WB. The Nematode. Caenorhabditis elegans. USA: ColdSpring Harbor Laboratory Press 1988.
33. Braeckman BP, Vanfleteren JR. Genetic control of longevity in C. elegans. Exp Gerontol 2007; 42: 90-8.
34. Riddle DL, Blumenthal T, Meyer BJ, Preiss JR, Eds. C. elegans II. USA: Cold Spring Harbor Laboratory Press 1997.
35. Klass MR. A method for the isolation of longevity mutants in thenematode Caenorhabditis elegans and initial results. Mech AgeingDev 1983; 22: 279-86.
36. Friedman DB, Johnson TE. A Mutation in the age-1 gene inCaenorhabditis elegans lengthens life and reduces hermaphroditefertility. Genetics 1988; 118: 75-86.
37. Hertweck M, Gobel C, Baumeister R. C. elegans SGK-1 is thecritical component in the Akt/PKB kinase complex to control stressresponse and life span. Dev Cell 2004; 6: 577-88.
38. Paradis S, Ailion M, Toker A, Thomas JH, Ruvkun G. A PDK1homolog is necessary and sufficient to transduce AGE-1 PI3 kinasesignals that regulate diapause in Caenorhabditis elegans. GenesDev 1999; 13: 1438-52.
39. Hamilton B, Doug YQ, Shindo M, Liu WY, Odell I, Ruvkun G, et al. A systematic RNAi screen for longevity genes in C-elegans. Genes Dev 2005; 19: 1544-55.
40. Tissenbaum HA, Guarente L. Increased dosage of a sir-2 geneextends lifespan in Caenorhabditis elegans. Nature 2001; 410: 227-30.
41. Allard JS, Perez E, Zou S, de Cabo R. Dietary activators of Sirt1. Mol Cell Endocrinol 2009; 299: 58-63.
42. Rine J, Herskowitz I. Four genes responsible for a position effecton expression from HML and HMR in Saccharomyces cerevisiae. Genetics 1987; 116: 9-22.
43. Berdichevsky A, Viswanathan M, Horvitz HR, Guarente L. C. elegans SIR-2.1 interacts with 14-3-3 proteins to activate DAF-16and extend life span. Cell 2006; 125: 1165-77.
44. Tanner KG, Landry J, Sternglanz R, Denu JM. Silent informationregulator 2 family of NAD- dependent histone/protein deacetylasesgenerates a unique product, 1-O-acetyl-ADP-ribose. Proc NatlAcad Sci USA 2000; 97: 14178-82.
45. Guarente L. Sir2 links chromatin silencing, metabolism, and aging. Genes Dev 2000; 14: 1021-6.
46. Rogina B, Helfand SL, Frankel S. Longevity regulation byDrosophila Rpd3 deacetylase and caloric restriction. Science 2002; 298: 1745.
47. McCay CM, Crowell MF, Maynard LA. The effect of retardedgrowth upon the length of life span and upon the ultimate bodysize. J Nutr 1935; 10: 63-79.
48. Wang YM, Tissenbaum HA. Overlapping and distinct functions fora Caenorhabditis elegans SIR2 and DAF-16/FOXO. Mech AgeingDev 2006; 127: 48-56.
49. Rogina B, Helfand SL. Sir2 mediates longevity in the fly through apathway related to calorie restriction. Proc Natl Acad Sci USA 2004; 101: 15998-6003.
50. Wood JG, Rogina B, Lavu S, Howitz K, Helfand SL, Tatar M, et al. Sirtuin activators mimic caloric restriction and delay ageing inmetazoans. Nature 2004; 430: 686-9.
51. Koubova J, Guarente L. How does calorie restriction work?. GenesDev 2003: 313-21.
52. Klass M, Hirsh D. Non-ageing developmental variant ofCaenorhabditis elegans. Nature 1976; 260: 523-5.
53. Bishop NA, Guarente L. Genetic links between diet and lifespan:shared mechanisms from yeast to humans. Nat Rev Genetics 2007; 8: 835-44.
54. Lee SJ, Murphy CT, Kenyon C. Glucose shortens the life span ofC. elegans by downregulating DAF-16/FOXO activity and aquaporin gene expression. Cell Metab 2009; 10: 379-91.
55. Vellai T, Takacs-Vellai K, Zhang Y, Kovacs AL, Orosz L, Muller F. Genetics: influence of TOR kinase on lifespan in C. elegans. Nature 2003; 426: 620.
56. Kapahi P, Zid BM, Harper T, Koslover D, Sapin V, Benzer S. Regulation of lifespan in Drosophila by modulation of genes in theTOR signaling pathway. Curr Biol 2004; 14: 885-90.
57. Melendez A, Talloczy Z, Seaman M, Eskelinen EL, Hall DH, Levine B. Autophagy genes are essential for dauer developmentand life-span extension in C. elegans. Science 2003; 301: 1387-91.
58. Jia KL, Thomas C, Akbar M, Sun QH, Adams-Huet B, Gilpin C, et al. Autophagy genes protect against Salmonella typhimuriuminfection and mediate insulin signaling-regulated pathogenresistance. Proc Natl Acad Sci USA 2009; 106: 14564-9.
59. Juhasz G, Puskaas LG, Komonyi O, Erdi B, Maroy P, Neufeld TP, et al. Gene expression profiling identifies FKBP39 as an inhibitorof autophagy in larval Drosophila fat body. Cell Death Differ 2007; 14: 1181-90.
60. Zhao J, Brault JJ, Schild A, Cao P, Sandri M, Schiaffino S, et al. FoxO3 coordinately activates protein degradation by theAutophagic/Lysosomal and proteasomal pathways in atrophyingmuscle cells. Cell Metab 2007; 6: 472-83.
61. Mammucari C, Milan G, Romanello V, Masiero E, Rudolf R, DelPiccolo P, et al. FoxO3 controls autophagy in skeletal muscle invivo. Cell Metab 2007; 6: 458-71.
62. Morselli E, Maiuri MC, Markaki M, Megalou E, Pasparaki A, Palikaras K, et al. The life span-prolonging effect of Sirtuin-1 ismediated by autophagy. Autophagy 2010; 6: 186-8.
63. Garsin DA, Villanueva JM, Begun J, Kim DH, Sifri CD, Calderwood SB, et al. Long-Lived C. elegans daf-2 mutants areresistant to bacterial pathogens. Science 2003; 300: 1921.
64. Evans EA, Kawli T, Tan MW. Pseudomonas aeruginosa suppresseshost immunity by activating the DAF-2 insulin-like signalingpathway in Caenorhabditis elegans. PLoS Pathog 2008; 4:e1000175.
65. Kim DH, Feinbaum R, Alloing G, Emerson FE, Garsin DA, Inoue H, et al. A conserved p38 MAP kinase pathway in Caenorhabditiselegans innate immunity. Science 2002; 297: 623-6.
66. Kim DH, Liberati NT, Mizuno T, Inoue H, Hisamoto N, Matsumoto K, et al. Integration of Caenorhabditis elegans MAPKpathways mediating immunity and stress resistance by MEK-1MAPK kinase and VHP-1 MAPK phosphatase. Proc Natl Acad SciUSA 2004; 101: 10990-4.
67. Nicholas HR, Hodgkin J. The ERK MAP kinase cascade mediatestail swelling and a protective response to rectal infection in C. elegans. Curr Biol 2004; 14: 1256-61.
68. Huffman DL, Abrami L, Sasik R, Corbeil J, van der Goot FG, Aroian RV. Mitogen-activated protein kinase pathways defendagainst bacterial pore-forming toxins. Proc Natl Acad Sci USA 2004; 101: 10995-1000.
69. Mallo GV, Kurz CL, Couillault C, Pujol N, Granjeaud S, Kohara Y, et al. Inducible antibacterial defense system in C. elegans. CurrBiol 2002; 12: 1209-14.
70. Aballay A, Ausubel FM. Programmed cell death mediated by ced-3and ced-4 protects Caenorhabditis elegans from Salmonellatyphimurium-mediated killing. Proc Natl Acad Sci USA 2001; 98: 2735-9.
71. Tenor JL, Aballay A. A conserved Toll-like receptor is required forCaenorhabditis elegans innate immunity. EMBO Rep 2008; 9: 103-9.
72. Irazoqui JE, Ng A, Xavier RJ, Ausubel FM. Role for beta-cateninand HOX transcription factors in Caenorhabditis elegans and mammalian host epithelial-pathogen interactions. Proc Natl AcadSci USA 2008; 105: 17469-74.
73. Nicholas HR, Hodgkin J. The C. elegans Hox gene egl-5 isrequired for correct development of the hermaphrodite hindgut and for the response to rectal infection by Microbacteriumnematophilum. Dev Biol 2009; 329: 16-24.
74. Kondo M, Yanase S, Ishii T, Hartman PS, Matsumoto K, Ishii N. The p38 signal transduction pathway participates in the oxidativestress-mediated translocation of DAF-16 to Caenorhabditis elegansnuclei. Mech Ageing Dev 2005; 126: 642-7.
75. Arik AJ, Rasgon JL, Quicke KM, Riehle MA. Manipulating insulinsignaling to enhance mosquito reproduction. BMC Physiol 2009; 9: 15.
76. Butcher RA, Fujita M, Schroeder FC, Clardy J. Small-moleculepheromones that control dauer development in Caenorhabditiselegans. Nat Chem Biol 2007; 3: 420-2.
77. Vowels JJ, Thomas JH. Genetic-analysis of chemosensory controlof dauer formation in caenorhabditis-elegans. Genetics 1992; 130: 105-23.
78. Gottlieb S, Ruvkun G. Daf-2, Daf-16 and Daf-23 - geneticallyinteracting genes-controlling dauer formation in Caenorhabditiselegans. Genetics 1994; 137: 107-20.
79. Riddle DL, Swanson MM, Albert PS. Interacting genes innematode dauer larva formation. Nature 1981; 290: 668-71.
80. Thomas JH, Birnby DA, Vowels JJ. Evidence for parallelprocessingof sensory information controlling dauer formation inCaenorhabditis-elegans. Genetics 1993; 134: 1105-17.
81. Morris JZ, Tissenbaum HA, Ruvkun G. A phosphatidylinositol-3-OH kinase family member regulating longevity and diapause inCaenorhabditis elegans. Nature 1996; 382: 536-9.
82. Kimura KD, Tissenbaum HA, Liu Y, Ruvkun G. daf-2, an insulinreceptor-like gene that regulates longevity and diapause inCaenorhabditis elegans. Science 1997; 277: 942-6.
83. Tatar M, Bartke A, Antebi A. The endocrine regulation of aging byinsulin-like signals. Science 2003; 299: 1346-51.
84. Longo VD. The Ras and Sch9 pathways regulate stress resistanceand longevity. Exp Gerontol 2003; 38: 807-11.
85. Holzenberger M, Dupont J, Ducos B, Leneuve P, Geloen A, Even PC, et al. IGF-1 receptor regulates lifespan and resistance tooxidative stress in mice. Nature 2003; 421: 182-7.
86. Bell R, Hubbard A, Chettier R, Chen D, Miller JP, Kapahi P, et al. A human protein interaction network shows conservation of agingprocesses between human and invertebrate species. Plos Genetics 2009; 5:
87. Pierce SB, Costa M, Wisotzkey R, Devadhar S, Homburger SA, Buchman AR, et al. Regulation of DAF-2 receptor signaling byhuman insulin and ins-1, a member of the unusually large and diverse C. elegans insulin gene family. Genes Dev 2001: 672-86.
88. Finch CE, Ruvkun G. The genetics of aging. Annu Rev GenomicsHum Genet 2001; 2: 435-62.
89. Iser WB, Gami MS, Wolkow CA. Insulin signaling inCaenorhabditis elegans regulates both endocrine-like and cellautonomousoutputs. Dev Biol 2007; 303: 434-47.
90. Ewbank JJ. Wormbook, Signaling in the immune response. The C. elegance Research Community 2006; pp. 1-12.
91. Brunet A, Bonni A, Zigmond MJ, Lin MZ, Juo P, Hu LS, et al. Aktpromotes cell survival by phosphorylating and inhibiting aForkhead transcription factor. Cell 1999; 96: 857-68.
92. Lin K, Hsin H, Libina N, Kenyon C. Regulation of theCaenorhabditis elegans longevity protein DAF-16 by insulin/IGF-1and germline signaling. Nat Genetics 2001; 28: 139-45.
93. Ogg S, Ruvkun G. The C. elegans PTEN Homolog, DAF-18, actsin the insulin receptor-like metabolic signaling pathway. Mol Cell 1998; 2: 887-93.
94. Chavez V, Mohri-Shiomi A, Maadani A, Vega LA, Garsin DA. Oxidative stress enzymes are required for daf-16-mediatedimmunity due to generation of reactive oxygen species byCaenorhabditis elegans. Genetics 2007; 176: 1567-77.
95. Li J, Tewari M, Vidal M, Lee SS. The 14-3-3 protein FTT-2regulates DAF-16 in Caenorhabditis elegans. Dev Biol 2007; 301: 82-91.
96. Ookuma S, Fukuda M, Nishida E. Identification of a DAF-16transcriptional target gene, scl-1, that regulates longevity and stressresistance in Caenorhabditis elegans. Curr Biol 2003; 13: 427-31.
97. Dorman JB, Albinder B, Shroyer T, Kenyon C. The age-1 and daf-2 genes function in a common pathway to control the lifespan ofCaenorhabditis elegans. Genetics 1995; 141: 1399-406.
98. Lee RYN, Hench J, Ruvkun G. Regulation of C. elegans DAF-16and its human ortholog FKHRL1 by the daf-2 insulin-like signalingpathway. Curr Biol 2001; 11: 1950-7.
99. Schaffitzel E, Hertweck M. Recent aging research inCaenorhabditis elegans. Exp Gerontol 2006; 41: 557-63.
100. Lee SS, Kennedy S, Tolonen AC, Ruvkun G. DAF-16 target genesthat control C-elegans life-span and metabolism. Science 2003; 300: 644-7.
101. Toivonen JM, Partridge L. Endocrine regulation of aging and reproduction in Drosophila. Mol Cell Endocrinol 2009; 299: 39-50.
102. Weinkove D, Leevers SJ. The genetic control of organ growth:insights from Drosophila. Curr Opin Genet Dev 2000; 10: 75-80.
103. Bohni R, Riesgo-Escovar J, Oldham S, Brogiolo W, Stocker H, Andruss BF, et al. Autonomous control of cell and organ size byCHICO, a Drosophila homolog of vertebrate IRS1-4. Cell 1999; 97: 865-75.
104. Leevers SJ, Weinkove D, MacDougall LK, Hafen E, Waterfield MD. The Drosophila phosphoinositide 3-kinase Dp110 promotescell growth. EMBO J 1996; 15: 6584-94.
105. Verdu J, Buratovich MA, Wilder EL, Birnbaum MJ. Cellautonomousregulation of cell and organ growth in Drosophila byAkt/PKB. Nat Cell Biol 1999; 1: 500-6.
106. Ogg S, Paradis S, Gottlieb S, Patterson GI, Lee L, Tissenbaum HA, et al. The Fork head transcription factor DAF-16 transducesinsulin-like metabolic and longevity signals in C-elegans. Nature 1997; 389: 994-9.
107. Alvarez B, Martinez AC, Burgering BM, Carrera AC. Forkheadtranscription factors contribute to execution of the mitoticprogramme in mammals. Nature 2001; 413: 744-7.
108. Kops GJ, Dansen TB, Polderman PE, Saarloos I, Wirtz KW, Coffer PJ, et al. Forkhead transcription factor FOXO3a protects quiescentcells from oxidative stress. Nature 2002; 419: 316-21.
109. Tran H, Brunet A, Grenier JM, Datta SR, Fornace AJ, DiStefano PS, et al. DNA repair pathway stimulated by the forkheadtranscription factor FOXO3a through the Gadd45 protein. Science 2002; 296: 530-4.
110. Navarro I, Leibush B, Moon TW, Plisetskaya EM, Banos N, Mendez E, et al. Insulin, insulin-like growth factor-I (IGF-I) and glucagon: the evolution of their receptors. Comp Biochem PhysiolB-Biochem Mol Biol 1999; 122: 137-53.
111. Saltiel AR, Kahn CR. Insulin signalling and the regulation ofglucose and lipid metabolism. Nature 2001; 414: 799-806.
112. Nakae J, Biggs WH, 3rd, Kitamura T, Cavenee WK, Wright CV, Arden KC, et al. Regulation of insulin action and pancreatic betacellfunction by mutated alleles of the gene encoding forkheadtranscription factor Foxo1. Nat Genet 2002; 32: 245-53.
113. Paik JH, Kollipara R, Chu G, Ji H, Xiao Y, Ding Z, et al. FoxOsare lineage-restricted redundant tumor suppressors and regulateendothelial cell homeostasis. Cell 2007; 128: 309-23.
114. Tothova Z, Kollipara R, Huntly BJ, Lee BH, Castrillon DH, Cullen DE, et al. FoxOs are critical mediators of hematopoietic stem cellresistance to physiologic oxidative stress. Cell 2007; 128: 325-39.
115. Naka K, Hoshii T, Muraguchi T, Tadokoro Y, Ooshio T, Kondo Y, et al. TGF-beta-FOXO signalling maintains leukaemia-initiatingcells in chronic myeloid leukaemia. Nature 2010; 463: 676-80.
116. Kops GJ, de Ruiter ND, De Vries-Smits AM, Powell DR, Bos JL, Burgering BM. Direct control of the Forkhead transcription factorAFX by protein kinase B. Nature 1999; 398: 630-4.
117. van der Horst A, de Vries-Smits AMM, Brenkman AB, van Triest MH, van den Broek N, Colland F, et al. FOXO4 transcriptionalactivity is regulated by monoubiquitination and USP7/HAUSP. NatCell Biol 2006; 8: 1064-73.
118. Matsuzaki H, Daitoku H, Hatta M, Aoyama H, Yoshimochi K, Fukamizu A. Acetylation of Foxo1 alters its DNA-binding abilityand sensitivity to phosphorylation. Proc Natl Acad Sci USA 2005; 102: 11278-83.
119. Brownawell AM, Kops GJ, Macara IG, Burgering BM. Inhibitionof nuclear import by protein kinase B (Akt) regulates thesubcellular distribution and activity of the forkhead transcriptionfactor AFX. Mol Cell Biol 2001; 21: 3534-46.
120. Obsilova V, Vecer J, Herman P, Pabianova A, Sulc M, Teisinger J, et al. 14-3-3 Protein interacts with nuclear localization sequence offorkhead transcription factor FoxO4. Biochemistry 2005; 44: 11608-17.
121. Rinner O, Mueller LN, Hubalek M, Muller M, Gstaiger M, Aebersold R. An integrated mass spectrometric and computationalframework for the analysis of protein interaction networks. NatBiotechnol 2007; 25: 345-52.
122. Brunet A, Kanai F, Stehn J, Xu J, Sarbassova D, Frangioni JV, et al. 14-3-3 transits to the nucleus and participates in dynamicnucleocytoplasmic transport. J Cell Biol 2002; 156: 817-28.
123. Boura E, Silhan J, Herman P, Vecer J, Sulc M, Teisinger J, et al. Both the N-terminal loop and wing W2 of the forkhead domain oftranscription factor Foxo4 are important for DNA binding. J BiolChem 2007: 8265-75.
124. Plas DR, Thompson CB. Akt activation promotes degradation oftuberin and FOXO3a via the proteasome. J Biol Chem 2003; 278: 12361-6.
125. Willcox BJ, Donlon TA, He Q, Chen R, Grove JS, Yano K, et al. FOXO3A genotype is strongly associated with human longevity. Proc Natl Acad Sci USA 2008: 13987-92.
126. Flachsbart F, Caliebe A, Kleindorp R, Blanche H, von Eller-Eberstein H, Nikolaus S, et al. Association of FOXO3A variationwith human longevity confirmed in German centenarians. ProcNatl Acad Sci USA 2009; 106: 2700-5.
127. Gerisch B, Rottiers V, Li D, Motola DL, Cummins CL, Lehrach H, et al. A bile acid-like steroid modulates Caenorhabditis eleganslifespan through nuclear receptor signaling. Proc Natl Acad SciUSA 2007 104: 5014-9.
128. Lin K, Dorman JB, Rodan A, Kenyon C. daf-16: an hnf-3/forkheadfamily member that can function to double the life-span ofcaenorhabditis elegans. Science 1997; 278: 1319-22.
129. Furuyama T, Nakazawa T, Nakano I, Mori N. Identification of thedifferential distribution patterns of mRNAs and consensus bindingsequences for mouse DAF-16 homologues. Biochem J 2000; 349: 629-34.
130. Mukhopadhyay A, Deplancke B, Walhout AJM, Tissenbaum HA. Chromatin immunoprecipitation (ChIP) coupled to detection byquantitative real-time PCR to study transcription factor binding toDNA in Caenorhabditis elegans. Nat Protocols 2008; 3: 698-709.
131. Van Der Heide LP, Hoekman MF, Smidt MP. The ins and outs ofFoxO shuttling: mechanisms of FoxO translocation and transcriptional regulation. Biochem J 2004; 380: 297-309.
132. Wolff S, Ma H, Burch D, Maciel GA, Hunter T, Dillin A. SMK-1, an essential regulator of DAF-16-mediated longevity. Cell 2006; 124: 1039-53.
133. Hahm JH, Kim S, Paik YK. Endogenous cGMP regulates adultlongevity via the insulin signaling pathway in Caenorhabditiselegans. Aging Cell 2009; 8: 473-83.
134. Libina N, Berman JR, Kenyon C. Tissue-specific activities of c. elegans daf-16 in the regulation of lifespan. Cell 2003; 115: 489-502.
135. Apfeld J, Kenyon C. Cell Nonautonomy of C. elegans daf-2function in the regulation of diapause and life span. Cell 1998; 95: 199-210.
136. Henderson ST, Johnson TE. daf-16 integrates developmental and environmental inputs to mediate aging in the nematodeCaenorhabditis elegans. Curr Biol 2001; 11: 1975-80.
137. Hsin H, Kenyon C. Signals from the reproductive system regulatethe lifespan of C-elegans. Nature 1999; 399: 362-6.
138. Flatt T, Min KJ, D'Alterio C, Villa-Cuesta E, Cumbers J, Lehmann R, et al. Drosophila, germ-line modulation of insulin signaling and lifespan. Proc Natl Acad Sci USA 2008; 105: 6368-73.
139. Cargill SL, Carey JR, Muller HG, Anderson G. Age of ovarydetermines remaining life expectancy in old ovariectomized mice. Aging Cell 2003; 2: 185-90.
140. Alper S, McElwee MK, Apfeld J, Lackford B, Freedman JH, Schwartz DA. The Caenorhabditis elegans germ line regulatesdistinct signaling pathways to control lifespan and innateimmunity. J Biol Chem 2009; 1822-8.
141. Arantes-Oliveira N, Apfeld J, Dillin A, Kenyon C. Regulation oflife-span by germ-line stem cells in Caenorhabditis elegans. Science 2002; 295: 502-5.
142. Schulenburg H, Kurz CL, Ewbank JJ. Evolution of the innateimmune system: the worm perspective. Immunol Rev 2004; 198: 36-58.
143. Longo VD, Fabrizio P. Regulation of longevity and stressresistance: a molecular strategy conserved from yeast to humans?Cell Mol Life Sci 2002; 59: 903-8.
144. van den Berg MC, Woerlee JZ, Ma H, May RC. Sex-dependentresistance to the pathogenic fungus Cryptococcus neoformans. Genetics 2006; 173: 677-83.
145. Inoue T, Ailion M, Poon S, Kim HK, Thomas JH, Sternberg PW. Genetic analysis of dauer formation in Caenorhabditis briggsae. Genetics 2007; 177: 809-18.
146. McCulloch D, Gems D. Evolution of male longevity bias innematodes. Aging Cell 2003; 2: 165-73.
147. Kiontke K, Sudhaus W. Ecology of Caenorhabditis species; FitchDHA. The C. elegance Research Community 2006.
148. Riddle DL, Blumenthal T, Meyer BJ, Priess JR. C. elegans II. USA: Cold Spring Harbor Laboratory Press 1997.