Genetics of aging in Caenorhabditis elegans

PLoS Genetics

Volumn 3, Issue 9, 2007, Pages 1565-1571

  Antebi, Adam ^a  

^a BAYLOR COLLEGE OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLIC GMP; G PROTEIN COUPLED RECEPTOR; GUANINE NUCLEOTIDE BINDING PROTEIN; MICRORNA; SOMATOMEDIN C; TRANSCRIPTION FACTOR DAF 16; TRANSCRIPTION FACTOR FOXO;

AGE 1 GENE; AGING; CAENORHABDITIS ELEGANS; DAF 16 GENE; DAF 2 GENE; DIET RESTRICTION; ENVIRONMENTAL FACTOR; GENETIC ANALYSIS; GENETIC CONSERVATION; HEREDITY; LIFESPAN; LONGEVITY; MOLECULAR EVOLUTION; MOLECULAR GENETICS; MUTATOR GENE; NONHUMAN; REVIEW; STOCHASTIC MODEL;

AGING; ANIMALS; CAENORHABDITIS ELEGANS; GENES, HELMINTH; LONGEVITY;

ANIMALIA; CAENORHABDITIS ELEGANS;

EID: 34848911606     PISSN: 15537390     EISSN: 15537404     Source Type: Journal    
DOI: 10.1371/journal.pgen.0030129     Document Type: Review

References (132)

1. Friedman DB, Johnson TE (1988) A mutation in the age-1 gene in C. elegans lengthens life and reduces hermaphrodite fertility. Genetics 118: 75-86.
2. 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: 461-464.
3. Morris JZ, Tissenbaum HA, Ruvkun G (1996) A phosphatidylinositol-3-OH kinase family member regulating longevity and diapause in C. elegans. Nature 382: 536-539.
4. 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 277: 942-946.
5. Ogg S, Paradis S, Gottlieb S, Patterson GI, Lee L, et al. (1997) The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans. Nature 389: 994-999.
6. 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 278: 1319-1322.
7. Clancy DJ, Gems D, Harshman LG, Oldham S, Stocker H, et al. (2001) Extension of life-span by loss of CHICO, a Drosophila insulin receptor substrate protein. Science 292: 104-106.
8. Tatar M, Kopelman A, Epstein D, Tu MP, Yin CM, et al. (2001) A mutant Drosophila insulin receptor homolog that extends life-span and impairs neuroendocrine function. Science 292: 107-110.
9. Bluher M, Kahn BB, Kahn CR (2003) Extended longevity in mice lacking the insulin receptor in adipose tissue. Science 299: 572-574.
10. Holzenberger M, Dupont J, Ducos B, Leneuve P, Geloen A, et al. (2003) IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice. Nature 421: 182-187.
11. Pierce SB, Costa M, Wisotzkey R, Devadhar S, Homburger SA, 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.
12. 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: 844-858.
13. 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: 2488-2498.
14. Ogg S, Ruvkun G (1998) The C. elegans PTEN homolog, DAF-18, acts in the insulin receptor-like metabolic signaling pathway. Mol Cell 2: 887-893.
15. 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: 1438-1452.
16. 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: 577-588.
17. 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: 7427-7432.
18. 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: 1950-1957.
19. 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: 139-145.
20. Henderson ST, Johnson TE (2001) daf-16 integrates developmental and environmental inputs to mediate aging in the nematode C. elegans. Curr Biol 11: 1975-1980.
21. 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: 1385-1393.
22. Murphy CT, McCarroll SA, Bargmann CI, Fraser A, Kamath RS, et al. (2003) Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans. Nature 424: 277-283.
23. Lee SS, Kennedy S, Tolonen AC, Ruvkun G (2003) DAF-16 target genes that control C. elegans life-span and metabolism. Science 300: 644-647.
24. Melendez A, Talloczy Z, Seaman M, Eskelinen EL, Hall DH, et al. (2003) Autophagy genes are essential for dauer development and life-span extension in C. elegans. Science 301: 1387-1391.
25. McElwee JJ, Schuster E, Blanc E, Thomas JH, Gems D (2004) Shared transcriptional signature in Caenorhabditis elegans Dauer larvae and long-lived daf-2 mutants implicates detoxification system in longevity assurance. J Biol Chem 279: 44533-44543.
26. Walker GA, Lithgow GJ (2003) Lifespan extension in C. elegans by a molecular chaperone dependent upon insulin-like signals. Aging Cell 2: 131-139.
27. Kenyon C (2005) The plasticity of aging: insights from long-lived mutants. Cell 120: 449-460.
28. Tatar M, Bartke A, Antebi A (2003) The endocrine regulation of aging by insulin-like signals. Science 299: 1346-1351.
29. Dillin A, Crawford DK, Kenyon C (2002) Timing requirements for insulin/ IGF-1 signaling in C. elegans. Science 298: 830-834.
30. Jenkins NL, McColl G, Lithgow GJ (2004) Fitness cost of extended lifespan in Caenorhabditis elegans. Proc Biol Sci 271: 2523-2526.
31. Hamilton B, Dong Y, Shindo M, Liu W, Odell I, et al. (2005) A systematic RNAi screen for longevity genes in C. elegans. Genes Dev 19: 1544-1555.
32. Hansen M, Hsu AL, Dillin A, Kenyon C (2005) New genes tied to endocrine, metabolic, and dietary regulation of lifespan from a Caenorhabditis elegans genomic RNAi screen. PLoS Genet 1: 119-128. doi:10.1371/journal. pgen.0010017
33. Dillin A, Hsu AL, Arantes-Oliveira N, Lehrer-Graiwer J, Hsin H, et al. (2002) Rates of behavior and aging specified by mitochondrial function during development. Science 298: 2398-2401.
34. Lee SS, Lee RY, Fraser AG, Kamath RS, Ahringer J, et al. (2003) A systematic RNAi screen identifies a critical role for mitochondria in C. elegans longevity. Nat Genet 33: 40-48.
35. Oh SW, Mukhopadhyay A, Dixit BL, Raha T, Green MR, et al. (2006) Identification of direct DAF-16 targets controlling longevity, metabolism and diapause by chromatin immunoprecipitation. Nat Genet 38: 251-257.
36. Cypser JR, Tedesco P, Johnson TE (2006) Hormesis and aging in Caenorhabditis elegans. Exp Gerontol 41: 935-939.
37. Apfeld J, Kenyon C (1999) Regulation of lifespan by sensory perception in Caenorhabditis elegans. Nature 402: 804-809.
38. Alcedo J, Kenyon C (2004) Regulation of C. elegans longevity by specific gustatory and olfactory neurons. Neuron 41: 45-55.
39. Ailion M, Inoue T, Weaver CI, Holdcraft RW, Thomas JH (1999) Neurosecretory control of aging in Caenorhabditis elegans. Proc Natl Acad Sci U S A 96: 7394-7397.
40. Munoz MJ, Riddle DL (2003) Positive selection of C. elegans mutants with increased stress resistance and longevity. Genetics 163: 171-180.
41. Mukhopadhyay A, Deplancke B, Walhout AJ, Tissenbaum HA (2005) C. elegans tubby regulates life span and fat storage by two independent mechanisms. Cell Metab 2: 35-42.
42. Lans H, Jansen G (2007) Multiple sensory G proteins in the olfactory, gustatory and nociceptive neurons modulate longevity in Caenorhabditis elegans. Dev Biol 303: 474-482.
43. Libert S, Zwiener J, Chu X, Vanvoorhies W, Roman G, et al. (2007) Regulation of Drosophila life span by olfaction and food-derived odors. Science 315: 1133-1137.
44. Murakami H, Murakami S (2007) Serotonin receptors antagonistically modulate C. elegans longevity. Aging Cell 6: 483-488.
45. Sze JY, Victor M, Loer C, Shi Y, Ruvkun G (2000) Food and metabolic signalling defects in a C. elegans serotonin-synthesis mutant. Nature 403: 560-564.
46. Liang B, Moussaif M, Kuan CJ, Gargus JJ, Sze JY (2006) Serotonin targets the DAF-16/FOXO signaling pathway to modulate stress responses. Cell Metab 4: 429-440.
47. Oh SW, Mukhopadhyay A, Svrzikapa N, Jiang F, Davis RJ, et al. (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.
48. Wang MC, Bohmann D, Jasper H (2005) JNK extends life span and limits growth by antagonizing cellular and organism-wide responses to insulin signaling. Cell 121: 115-125.
49. Wang MC, Bohmann D, Jasper H (2003) JNK signaling confers tolerance to oxidative stress and extends lifespan in Drosophila. Dev Cell 5: 811-816.
50. Lehtinen MK, Yuan Z, Boag PR, Yang Y, Villen J, et al. (2006) A conserved MST-FOXO signaling pathway mediates oxidative-stress responses and extends life span. Cell 125: 987-1001.
51. Troemel ER, Chu SW, Reinke V, Lee SS, Ausubel FM, et al. (2006) p38 MAPK regulates expressionof immune response genes and contributes to longevity in C. elegans. PLoS Genet 2: e183. doi:10.1371/journal.pgen.0020183
52. Nanji M, Hopper NA, Gems D (2005) LET-60 RAS modulates effects of insulin/IGF-1 signaling on development and aging in Caenorhabditis elegans. Aging Cell 4: 235-245.
53. 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: 3004-3009.
54. 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: 235-246.
55. Wolff S, Ma H, Burch D, Maciel GA, Hunter T, et al. (2006) SMK-1, an essential regulator of DAF-16-mediated longevity. Cell 124: 1039-1053.
56. Hsu AL, Murphy CT, Kenyon C (2003) Regulation of aging and age-related disease by DAF-16 and heat-shock factor. Science 300: 1142-1145.
57. Morley JF, Morimoto RI (2004) Regulation of longevity in Caenorhabditis elegans by heat shock factor and molecular chaperones. Mol Biol Cell 15: 657-664.
58. Singh V, 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.
59. Essers MA, de Vries-Smits LM, Barker N, Polderman PE, Burgering BM, et al. (2005) Functional interaction between beta-catenin and FOXO in oxidative stress signaling. Science 308: 1181-1184.
60. Kaeberlein M, McVey M, Guarente L (1999) The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes Dev 13: 2570-2580.
61. Tissenbaum HA, Guarente L (2001) Increased dosage of a sir-2 gene extends lifespan in C. elegans. Nature 410: 227-230.
62. Rogina B, Helfand SL (2004) Sir2 mediates longevity in the fly through a pathway related to calorie restriction. Proc Natl Acad Sci U S A 101: 15998-16003.
63. Luo J, Nikolaev AY, Imai S, Chen D, Su F, et al. (2001) Negative control of p53 by Sir2alpha promotes cell survival under stress. Cell 107: 137-148.
64. Vaziri H, Dessain SK,Ng Eaton E, Imai SI, Frye RA, et al. (2001) hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase. Cell 107: 149-159.
65. MottaMC, Divecha N, LemieuxM, Kamel C, Chen D, et al. (2004) Mammalian SIRT1 represses forkhead transcription factors. Cell 116: 551-563.
66. Brunet A, Sweeney LB, Sturgill JF, Chua KF, Greer PL, et al. (2004) Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science 303: 2011-2015.
67. Nemoto S, Fergusson MM, Finkel T (2005) SIRT1 functionally interacts with the metabolic regulator and transcriptional coactivator PGC-1{alpha}. J Biol Chem 280: 16456-16460.
68. 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: 1165-1177.
69. Wang Y, Oh SW, Deplancke B, Luo J, Walhout AJ, et al. (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.
70. Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, et al. (2003) Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 425: 191-196.
71. Wood JG, Rogina B, Lavu S, Howitz K, Helfand SL, et al. (2004) Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Nature 430: 686-689.
72. Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, et al. (2006) Resveratrol improves health and survival of mice on a high-calorie diet. Nature 444: 337-342.
73. Viswanathan M, Kim SK, Berdichevsky A, Guarente L (2005) A role for SIR-2.1 regulation of ER stress response genes in determining C. elegans life span. Dev Cell 9: 605-615.
74. Urano F, Calfon M, Yoneda T, Yun C, Kiraly M, et al. (2002) A survival pathway for Caenorhabditis elegans with a blocked unfolded protein response. J Cell Biol 158: 639-646.
75. Arantes-Oliveira N, Apfeld J, Dillin A, Kenyon C (2002) Regulation of lifespan by germ-line stem cells in Caenorhabditis elegans. Science 295: 502-505.
76. Hsin H, Kenyon C (1999) Signals from the reproductive system regulate the lifespan of C. elegans. Nature 399: 362-366.
77. Berman JR, Kenyon C (2006) Germ-cell loss extends C. elegans life span through regulation of DAF-16 by kri-1 and lipophilic-hormone signaling. Cell 124: 1055-1068.
78. Rottiers V, Motola DL, Gerisch B, Cummins CL, Nishiwaki K, et al. (2006) Hormonal control of C. elegans dauer formation and life span by a Rieske-like oxygenase. Developmental Cell 10: 473-482.
79. Gerisch B, Weitzel C, Kober-Eisermann C, Rottiers V, Antebi A (2001) A hormonal signaling pathway influencing C. elegans metabolism, reproductive development, and life span. Dev Cell 1: 841-851.
80. Gerisch B, Rottiers V, Li D, Motola DL, Cummins CL, et al. (2007) A bile acid-like steroid modulates C. elegans lifespan through nuclear receptor signaling. PNAS 104: 5014-5019.
81. Motola DL, Cummins CL, Rottiers V, Sharma K, Sunino K, et al. (2006) Identification of DAF-12 ligands that govern dauer formation and reproduction in C. elegans. Cell 124: 1209-1223.
82. Held JM, White MP, Fisher AL, Gibson BW, Lithgow GJ, et al. (2006) DAF-12-dependent rescue of dauer formation in Caenorhabditis elegans by (25S)-cholestenoic acid. Aging Cell 5: 283-291.
83. Song C, Liao S (2000) Cholestenoic acid is a naturally occurring ligand for liver X receptor alpha. Endocrinology 141: 4180-4184.
84. Broue F, Liere P, Kenyon C, Baulieu EE (2007) A steroid hormone that extends the lifespan of Caenorhabditis elegans. Aging Cell 6: 87-94.
85. Jia K, Albert PS, Riddle DL (2002) DAF-9, a cytochrome P450 regulating C. elegans larval development and adult longevity. Development 129: 221-231.
86. Ludewig AH, Kober-Eisermann C, Weitzel C, Bethke A, Neubert K, et al. (2004) A novel nuclear receptor/coregulator complex controls C. elegans lipid metabolism, larval development, and aging. Genes Dev 18: 2120-2133.
87. Lee RC, Feinbaum RL, Ambros V (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75: 843-854.
88. Wightman B, Ha I, Ruvkun G (1993) Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell 75: 855-862.
89. Boehm M, Slack F (2005) A developmental timing microRNA and its target regulate life span in C. elegans. Science 310: 1954-1957.
90. Hristova M, Birse D, Hong Y, Ambros V (2005) The Caenorhabditis elegans heterochronic regulator LIN-14 is a novel transcription factor that controls the developmental timing of transcription from the insulin/ insulin-like growth factor gene ins-33 by direct DNA binding. Mol Cell Biol 25: 11059-11072.
91. Ibanez-Ventoso C, Yang M, Guo S, Robins H, Padgett RW, et al. (2006) Modulated microRNA expression during adult lifespan in Caenorhabditis elegans. Aging Cell 5: 235-246.
92. Olsen A, Vantipalli MC, Lithgow GJ (2006) Checkpoint proteins control survival of the postmitotic cells in Caenorhabditis elegans. Science 312: 1381-1385.
93. Lakowski B, Hekimi S (1996) Determination of life-span in Caenorhabditis elegans by four clock genes. Science 272: 1010-1013.
94. Campisi J (2003) Cancer and ageing: rival demons? Nat Rev Cancer 3: 339-349.
95. Jonassen T, Proft M, Randez-Gil F, Schultz JR, Marbois BN, et al. (1998) Yeast Clk-1 homologue (Coq7/Cat5) is a mitochondrial protein in coenzyme Q synthesis. J Biol Chem 273: 3351-3357.
96. Feng J, Bussiere F, Hekimi S (2001) Mitochondrial electron transport is a key determinant of life span in Caenorhabditis elegans. Dev Cell 1: 633-644.
97. Braeckman BP, Houthoofd K, Brys K, Lenaerts I, De Vreese A, et al. (2002) No reduction of energy metabolism in Clk mutants. Mech Ageing Dev 123: 1447-1456.
98. Kayser EB, Sedensky MM, Morgan PG, Hoppel CL (2004) Mitochondrial oxidative phosphorylation is defective in the long-lived mutant clk-1. J Biol Chem 279: 54479-54486.
99. Ventura N, Rea SL, Testi R (2006) Long-lived C. elegans mitochondrial mutants as a model for human mitochondrial-associated diseases. Exp Gerontol 41: 974-991.
100. Curtis R, O'Connor G, DiStefano PS (2006) Aging networks in Caenorhabditis elegans: AMP-activated protein kinase (aak-2) links multiple aging and metabolism pathways. Aging Cell 5: 119-126.
101. Liu X, Jiang N, Hughes B, Bigras E, Shoubridge E, et al. (2005) Evolutionary conservation of the clk-1-dependent mechanism of longevity: loss of mclk1 increases cellular fitness and lifespan in mice. Genes Dev 19: 2424-2434.
102. Klass MR (1977) Aging in the nematode C. elegans: major biological and environmental factors influencing life span. Mech Ageing Dev 6: 413-429.
103. Houthoofd K, Braeckman BP, Johnson TE, Vanfleteren JR (2003) Life extension via dietary restriction is independent of the Ins/IGF-1 signalling pathway in Caenorhabditis elegans. Exp Gerontol 38: 947-954.
104. Lakowski B, Hekimi S (1998) The genetics of caloric restriction in Caenorhabditis elegans. Proc Natl Acad Sci U S A 95: 13091-13096.
105. Lee GD, Wilson MA, Zhu M, Wolkow CA, de Cabo R, et al. (2006) Dietary deprivation extends lifespan in Caenorhabditis elegans. Aging Cell 5: 515-524.
106. Kaeberlein TL, Smith ED, Tsuchiya M, Welton KL, Thomas JH, et al. (2006) Lifespan extension in Caenorhabditis elegans by complete removal of food. Aging Cell 5: 487-494.
107. Panowski SH, Wolff S, Aguilaniu H, Durieux J, Dillin A (2007) PHA-4/ Foxa mediates diet-restriction-induced longevity of C. elegans. Nature 447: 550-555.
108. Bishop NA, Guarente L (2007) Two neurons mediate diet-restriction-induced longevity in C. elegans. Nature 447: 545-549.
109. Bowerman B, Eaton BA, Priess JR (1992) skn-1, a maternally expressed gene required to specify the fate of ventral blastomeres in the early C. elegans embryo. Cell 68: 1061-1075.
110. An JH, Blackwell TK (2003) SKN-1 links C. elegans mesendodermal specification to a conserved oxidative stress response. Genes Dev 17: 1882-1893.
111. Mango SE, Lambie EJ, Kimble J (1994) The pha-4 gene is required to generate the pharyngeal primordium of Caenorhabditis elegans. Development 120: 3019-3031.
112. Friedman JR, Kaestner KH (2006) The Foxa family of transcription factors in development and metabolism. Cell Mol Life Sci 63: 2317-2328.
113. Lin SJ, Defossez PA, Guarente L (2000) Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae. Science 289: 2126-2128.
114. Kaeberlein M, Kirkland KT, Fields S, Kennedy BK (2004) Sir2-independent life span extension by calorie restriction in yeast. PLoS Biol 2: e296. doi:10. 1371/journal.pbio.0020296
115. Hansen M, Taubert S, Crawford D, Libina N, Lee SJ, et al. (2007) Lifespan extension by conditions that inhibit translation in Caenorhabditis elegans. Aging Cell 6: 95-110.
116. Wang Y, Tissenbaum HA (2006) Overlapping and distinct functions for a Caenorhabditis elegans SIR2 and DAF-16/FOXO. Mech Ageing Dev 127: 48-56.
117. Kapahi P, Zid BM, Harper T, Koslover D, Sapin V, et al. (2004) Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway. Curr Biol 14: 885-890.
118. Kaeberlein M, Powers RW 3rd, Steffen KK, Westman EA, Hu D, et al. (2005) Regulation of yeast replicative life span by TOR and Sch9 in response to nutrients. Science 310: 1193-1196.
119. Vellai T, Takacs-Vellai K, Zhang Y, Kovacs AL, Orosz L, et al. (2003) Genetics: influence of TOR kinase on lifespan in C. elegans. Nature 426: 620.
120. Jia K, Chen D, Riddle DL (2004) The TOR pathway interacts with the insulin signaling pathway to regulate C. elegans larval development, metabolism and life span. Development 131: 3897-3906.
121. Pan KZ, Palter JE, Rogers AN, Olsen A, Chen D, et al. (2007) Inhibition of mRNA translation extends lifespan in Caenorhabditis elegans. Aging Cell 6: 111-119.
122. Henderson ST, Bonafe M, Johnson TE (2006) daf-16 protects the nematode Caenorhabditis elegans during food deprivation. J Gerontol A Biol Sci Med Sci 61: 444-460.
123. Syntichaki P, Troulinaki K, TavernarakisN(2007) eIF4E function in somatic cells modulates ageing in Caenorhabditis elegans. Nature 445: 922-926.
124. Huang C, Xiong C, Kornfeld K (2004) Measurements of age-related changes of physiological processes that predict lifespan of Caenorhabditis elegans. Proc Natl Acad Sci U S A 101: 8084-8089.
125. Herndon LA, Schmeissner PJ, Dudaronek JM, Brown PA, Listner KM, et al. (2002) Stochastic and genetic factors influence tissue-specific decline in ageing C. elegans. Nature 419: 808-814.
126. Garigan D, Hsu AL, Fraser AG, Kamath RS, Ahringer J, et al. (2002) Genetic analysis of tissue aging in Caenorhabditis elegans: a role for heatshock factor and bacterial proliferation. Genetics 161: 1101-1112.
127. Golden TR, Beckman KB, Lee AH, Dudek N, Hubbard A, et al. (2007) Dramatic age-related changes in nuclear and genome copy number in the nematode Caenorhabditis elegans. Aging Cell 6: 179-188
128. Ishii N, Goto S, Hartman PS (2002) Protein oxidation during aging of the nematode Caenorhabditis elegans. Free Radic Biol Med 33: 1021-1025.
129. Gerstbrein B, Stamatas G, Kollias N, Driscoll M (2005) In vivo spectrofluorimetry reveals endogenous biomarkers that report healthspan and dietary restriction in Caenorhabditis elegans. Aging Cell 4: 127-137.
130. Rea SL, Wu D, Cypser JR, Vaupel JW, Johnson TE (2005) A stress-sensitive reporter predicts longevity in isogenic populations of Caenorhabditis elegans. Nat Genet 37: 894-898.
131. Cohen E, Bieschke J, Perciavalle RM, Kelly JW, Dillin A (2006) Opposing activities protect against age-onset proteotoxicity. Science 313: 1604-1610.
132. Pinkston JM, GariganD, Hansen M, KenyonC(2006) Mutations that increase the life span of C. elegans inhibit tumor growth. Science 313: 971-975.