Role of TOR signaling in aging and related biological processes in Drosophila melanogaster

Experimental Gerontology

Volumn 46, Issue 5, 2011, Pages 382-390

  Katewa, Subhash D ^a   Kapahi, Pankaj ^a  

^a BUCK INSTITUTE FOR RESEARCH ON AGING   (United States)

Author keywords

Aging; Caloric restriction; Dietary restriction; Drosophila; Lifespan; Nutrients; Rapamycin; TOR

Indexed keywords

DROSOPHILA PROTEIN; GROWTH FACTOR; INITIATION FACTOR 4E BINDING PROTEIN; MESSENGER RNA; S6 KINASE; TARGET OF RAPAMYCIN KINASE; TUBERIN; TUBEROUS SCLEROSIS 1; UNCLASSIFIED DRUG;

AGING; ARTICLE; AUTOPHAGY; CELL GROWTH; CELL PROLIFERATION; CELL STRESS; CELL SURVIVAL; DIET RESTRICTION; DROSOPHILA MELANOGASTER; ENVIRONMENTAL FACTOR; ENZYME ACTIVITY; EUKARYOTE; FEEDING BEHAVIOR; GENE; GERIATRIC DISORDER; GROWTH REGULATION; LIFESPAN; LONGEVITY; NONHUMAN; OXIDATIVE STRESS; PRIORITY JOURNAL; PROTEIN SYNTHESIS REGULATION; PROTEIN TARGETING; RHEB GENE; RNA METABOLISM; RNA SYNTHESIS; RNA TRANSCRIPTION; RNA TRANSLATION; SIGNAL TRANSDUCTION;

AGING; ANIMALS; DROSOPHILA MELANOGASTER; DROSOPHILA PROTEINS; MODELS, ANIMAL; PROTEIN KINASES; SIGNAL TRANSDUCTION;

DROSOPHILA MELANOGASTER; EUKARYOTA; MAMMALIA;

EID: 79954632599     PISSN: 05315565     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.exger.2010.11.036     Document Type: Article

References (137)

1. Vezina C., Kudelski A., Sehgal S.N. Rapamycin (AY-22, 989), a new antifungal antibiotic. I. Taxonomy of the producing streptomycete and isolation of the active principle. J Antibiot Tokyo 1975, 28:721-726.
2. Heitman J., Movva N.R., Hall M.N. Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast. Science 1991, 253:905-909.
3. Martin D.E., Hall M.N. The expanding TOR signaling network. Curr. Opin. Cell Biol. 2005, 17:158-166.
4. Dann S.G., Selvaraj A., Thomas G. mTOR Complex1-S6K1 signaling: at the crossroads of obesity, diabetes and cancer. Trends Mol. Med. 2007, 13:252-259.
5. Sabatini D.M. mTOR and cancer: insights into a complex relationship. Nat. Rev. Cancer 2006, 6:729-734.
6. Um S.H., D'Alessio D., Thomas G. Nutrient overload, insulin resistance, and ribosomal protein S6 kinase 1, S6K1. Cell Metab. 2006, 3:393-402.
7. Wullschleger S., Loewith R., Hall M.N. TOR signaling in growth and metabolism. Cell 2006, 124:471-484.
8. Jacinto E., Loewith R., Schmidt A., Lin S., Ruegg M.A., Hall A., Hall M.N. Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive. Nat. Cell Biol. 2004, 6:1122-1128.
9. Long X., Spycher C., Han Z.S., Rose A.M., Muller F., Avruch J. TOR deficiency in C. elegans causes developmental arrest and intestinal atrophy by inhibition of mRNA translation. Curr. Biol. 2002, 12:1448-1461.
10. Jia K., Chen D., Riddle D.L. The TOR pathway interacts with the insulin signaling pathway to regulate C. elegans larval development, metabolism and life span. Development 2004, 131:3897-3906.
11. Hentges K.E., Sirry B., Gingeras A.C., Sarbassov D., Sonenberg N., Sabatini D., Peterson A.S. FRAP/mTOR is required for proliferation and patterning during embryonic development in the mouse. Proc. Natl Acad. Sci. USA 2001, 98:13796-13801.
12. Murakami M., Ichisaka T., Maeda M., Oshiro N., Hara K., Edenhofer F., Kiyama H., Yonezawa K., Yamanaka S. mTOR is essential for growth and proliferation in early mouse embryos and embryonic stem cells. Mol. Cell. Biol. 2004, 24:6710-6718.
13. Bentzinger C.F., Romanino K., Cloetta D., Lin S., Mascarenhas J.B., Oliveri F., Xia J., Casanova E., Costa C.F., Brink M., Zorzato F., Hall M.N., Ruegg M.A. Skeletal muscle-specific ablation of raptor, but not of rictor, causes metabolic changes and results in muscle dystrophy. Cell Metab. 2008, 8:411-424.
14. Inoki K., Guan K.L. Complexity of the TOR signaling network. Trends Cell Biol. 2006, 16:206-212.
15. Blagosklonny M.V. Aging and immortality: quasi-programmed senescence and its pharmacologic inhibition. Cell Cycle 2006, 5:2087-2102.
16. Demidenko Z.N., Zubova S.G., Bukreeva E.I., Pospelov V.A., Pospelova T.V., Blagosklonny M.V. Rapamycin decelerates cellular senescence. Cell Cycle 2009, 8:1888-1895.
17. Demidenko Z.N., Blagosklonny M.V. Growth stimulation leads to cellular senescence when the cell cycle is blocked. Cell Cycle 2008, 7:3355-3361.
18. Kapahi P., Chen D., Rogers A.N., Katewa S.D., Li P.W., Thomas E.L., Kockel L. With TOR, less is more: a key role for the conserved nutrient-sensing TOR pathway in aging. Cell Metab. 2010, 11:453-465.
19. Rogers A.N., Kapahi P. Genetic mechanisms of lifespan extension by dietary restriction. Drug Discov. Today Dis. Mech. 2006, 3:6-10.
20. Stewart M.J., Berry C.O., Zilberman F., Thomas G., Kozma S.C. The Drosophila p70s6k homolog exhibits conserved regulatory elements and rapamycin sensitivity. Proc. Natl Acad. Sci. USA 1996, 93:10791-10796.
21. Watson K.L., Chou M.M., Blenis J., Gelbart W.M., Erikson R.L. A Drosophila gene structurally and functionally homologous to the mammalian 70-kDa s6 kinase gene. Proc. Natl Acad. Sci. USA 1996, 93:13694-13698.
22. Montagne J., Stewart M.J., Stocker H., Hafen E., Kozma S.C., Thomas G. Drosophila S6 kinase: a regulator of cell size. Science 1999, 285:2126-2129.
23. Barcelo H., Stewart M.J. Altering Drosophila S6 kinase activity is consistent with a role for S6 kinase in growth. Genesis 2002, 34:83-85.
24. Oldham S., Montagne J., Radimerski T., Thomas G., Hafen E. Genetic and biochemical characterization of dTOR, the Drosophila homolog of the target of rapamycin. Genes Dev. 2000, 14:2689-2694.
25. Zhang H., Stallock J.P., Ng J.C., Reinhard C., Neufeld T.P. Regulation of cellular growth by the Drosophila target of rapamycin dTOR. Genes Dev. 2000, 14:2712-2724.
26. Goberdhan D.C., Paricio N., Goodman E.C., Mlodzik M., Wilson C. Drosophila tumor suppressor PTEN controls cell size and number by antagonizing the Chico/PI3-kinase signaling pathway. Genes Dev. 1999, 13:3244-3258.
27. Britton J.S., Edgar B.A. Environmental control of the cell cycle in Drosophila: nutrition activates mitotic and endoreplicative cells by distinct mechanisms. Development 1998, 125:2149-2158.
28. Gao X., Pan D. TSC1 and TSC2 tumor suppressors antagonize insulin signaling in cell growth. Genes Dev. 2001, 15:1383-1392.
29. Tapon N., Ito N., Dickson B.J., Treisman J.E., Hariharan I.K. The Drosophila tuberous sclerosis complex gene homologs restrict cell growth and cell proliferation. Cell 2001, 105:345-355.
30. Gao X., Zhang Y., Arrazola P., Hino O., Kobayashi T., Yeung R.S., Ru B., Pan D. Tsc tumour suppressor proteins antagonize amino-acid-TOR signalling. Nat. Cell Biol. 2002, 4:699-704.
31. Radimerski T., Montagne J., Hemmings-Mieszczak M., Thomas G. Lethality of Drosophila lacking TSC tumor suppressor function rescued by reducing dS6K signaling. Genes Dev. 2002, 16:2627-2632.
32. Zhang Y., Gao X., Saucedo L.J., Ru B., Edgar B.A., Pan D. Rheb is a direct target of the tuberous sclerosis tumour suppressor proteins. Nat. Cell Biol. 2003, 5:578-581.
33. Stocker H., Radimerski T., Schindelholz B., Wittwer F., Belawat P., Daram P., Breuer S., Thomas G., Hafen E. Rheb is an essential regulator of S6K in controlling cell growth in Drosophila. Nat. Cell Biol. 2003, 5:559-565.
34. Saucedo L.J., Gao X., Chiarelli D.A., Li L., Pan D., Edgar B.A. Rheb promotes cell growth as a component of the insulin/TOR signalling network. Nat. Cell Biol. 2003, 5:566-571.
35. Bernal A., Kimbrell D.A. Drosophila Thor participates in host immune defense and connects a translational regulator with innate immunity. Proc. Natl Acad. Sci. USA 2000, 97:6019-6024.
36. Raught B., Gingras A.C., Gygi S.P., Imataka H., Morino S., Gradi A., Aebersold R., Sonenberg N. Serum-stimulated, rapamycin-sensitive phosphorylation sites in the eukaryotic translation initiation factor 4GI. EMBO J. 2000, 19:434-444.
37. Miron M., Verdu J., Lachance P.E., Birnbaum M.J., Lasko P.F., Sonenberg N. The translational inhibitor 4E-BP is an effector of PI(3)K/Akt signalling and cell growth in Drosophila. Nat. Cell Biol. 2001, 3:596-601.
38. Kim E., Goraksha-Hicks P., Li L., Neufeld T.P., Guan K.L. Regulation of TORC1 by Rag GTPases in nutrient response. Nat. Cell Biol. 2008, 10:935-945.
39. Li L., Kim E., Yuan H., Inoki K., Goraksha-Hicks P., Schiesher R.L., Neufeld T.P., Guan K.L. Regulation of mTORC1 by the rab and ARF GTPases. J. Biol. Chem. 2010, 186:703-711.
40. Lee S.J., Feldman R., O'Farrell P.H. An RNA interference screen identifies a novel regulator of target of rapamycin that mediates hypoxia suppression of translation in Drosophila S2 cells. Mol. Biol. Cell 2008, 19:4051-4061.
41. Hahn K., Miranda M., Francis V.A., Vendrell J., Zorzano A., Teleman A.A. PP2A regulatory subunit PP2A-B? counteracts S6K phosphorylation. Cell Metab. 2010, 11:438-444.
42. Polak P., Hall M.N. mTOR and the control of whole body metabolism. Curr. Opin. Cell Biol. 2009, 21:209-218.
43. Kapahi P., Zid B.M., Harper T., Koslover D., Sapin V., Benzer S. Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway. Curr. Biol. 2004, 14:885-890.
44. Bjedov I., Toivonen J.M., Kerr F., Slack C., Jacobson J., Foley A., Partridge L. Mechanisms of life span extension by rapamycin in the fruit fly Drosophila melanogaster. Cell Metab. 2010, 11:35-46.
45. Luong N., Davies C.R., Wessells R.J., Graham S.M., King M.T., Veech R., Bodmer R., Oldham S.M. Activated FOXO-mediated insulin resistance is blocked by reduction of TOR activity. Cell Metab. 2006, 4:133-142.
46. Giannakou M.E., Goss M., Junger M.A., Hafen E., Leevers S.J., Partridge L. Long-lived Drosophila with overexpressed dFOXO in adult fat body. Science 2004, 305:361.
47. Hwangbo D.S., Gershman B., Tu M.P., Palmer M., Tatar M. Drosophila dFOXO controls lifespan and regulates insulin signalling in brain and fat body. Nature 2004, 429:562-566.
48. Bluher M., Kahn B.B., Kahn C.R. Extended longevity in mice lacking the insulin receptor in adipose tissue. Science 2003, 299:572-574.
49. Kapahi P., Zid B. TOR pathway: linking nutrient sensing to life span. Sci Aging Knowledge Environ 2004 2004, PE34.
50. Oldham S., Hafen E. Insulin/IGF and target of rapamycin signaling: a TOR de force in growth control. Trends Cell Biol. 2003, 13:79-85.
51. Clancy D.J., Gems D., Hafen E., Leevers S.J., Partridge L. Dietary restriction in long-lived dwarf flies. Science 2002, 296:319.
52. Mair W., Goymer P., Pletcher S.D., Partridge L. Demography of dietary restriction and death in Drosophila. Science 2003, 301:1731-1733.
53. Rogina B., Helfand S.L., Frankel S. Longevity regulation by Drosophila Rpd3 deacetylase and caloric restriction. Science 2002, 298:1745.
54. Mair W., Piper M.D., Partridge L. Calories do not explain extension of life span by dietary restriction in Drosophila. PLoS Biol. 2005, 3:e223.
55. Katewa S.D., Kapahi P. Dietary restriction and aging, 2009. Aging Cell 2010, 9:105-112.
56. Bradley G.L., Leevers S.J. Amino acids and the humoral regulation of growth: fat bodies use slimfast. Cell 2003, 114:656-658.
57. Neufeld T.P. Genetic analysis of TOR signaling in Drosophila. Curr. Top. Microbiol. Immunol. 2004, 279:139-152.
58. Marygold S.J., Leevers S.J. Growth signaling: TSC takes its place. Curr. Biol. 2002, 12:R785-R787.
59. Shamji A.F., Nghiem P., Schreiber S.L. Integration of growth factor and nutrient signaling: implications for cancer biology. Mol. Cell 2003, 12:271-280.
60. Inoki K., Li Y., Xu T., Guan K.L. Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling. Genes Dev. 2003, 17:1829-1834.
61. Manning B.D., Cantley L.C. Rheb fills a GAP between TSC and TOR. Trends Biochem. Sci. 2003, 28:573-576.
62. Colombani J., Raisin S., Pantalacci S., Radimerski T., Montagne J., Leopold P. A nutrient sensor mechanism controls Drosophila growth. Cell 2003, 114:739-749.
63. Geminard C., Rulifson E.J., Leopold P. Remote control of insulin secretion by fat cells in Drosophila. Cell Metab. 2009, 10:199-207.
64. Wu M.Y., Cully M., Andersen D., Leevers S.J. Insulin delays the progression of Drosophila cells through G2/M by activating the dTOR/dRaptor complex. EMBO J. 2007, 26:371-379.
65. Harvey K.F., Mattila J., Sofer A., Bennett F.C., Ramsey M.R., Ellisen L.W., Puig O., Hariharan I.K. FOXO-regulated transcription restricts overgrowth of Tsc mutant organs. J. Cell Biol. 2008, 180:691-696.
66. Lamouille S., Derynck R. Cell size and invasion in TGF-beta-induced epithelial to mesenchymal transition is regulated by activation of the mTOR pathway. J. Cell Biol. 2007, 178:437-451.
67. Hennig K.M., Colombani J., Neufeld T.P. TOR coordinates bulk and targeted endocytosis in the Drosophila melanogaster fat body to regulate cell growth. J. Cell Biol. 2006, 173:963-974.
68. Bronk P., Wenniger J.J., Dawson-Scully K., Guo X., Hong S., Atwood H.L., Zinsmaier K.E. Drosophila Hsc70-4 is critical for neurotransmitter exocytosis in vivo. Neuron 2001, 30:475-488.
69. Layalle S., Arquier N., Leopold P. The TOR pathway couples nutrition and developmental timing in Drosophila. Dev. Cell 2008, 15:568-577.
70. Martin G.M., Austad S.N., Johnson T.E. Genetic analysis of ageing: role of oxidative damage and environmental stresses. Nat. Genet. 1996, 13:25-34.
71. Urban J., Soulard A., Huber A., Lippman S., Mukhopadhyay D., Deloche O., Wanke V., Anrather D., Ammerer G., Riezman H., Broach J.R., De Virgilio C., Hall M.N., Loewith R. Sch9 is a major target of TORC1 in Saccharomyces cerevisiae. Mol. Cell 2007, 26:663-674.
72. Hansen M., Taubert S., Crawford D., Libina N., Lee S.J., Kenyon C. Lifespan extension by conditions that inhibit translation in Caenorhabditis elegans. Aging Cell 2007, 6:95-110.
73. Kaeberlein M., Powers R.W., Steffen K.K., Westman E.A., Hu D., Dang N., Kerr E.O., Kirkland K.T., Fields S., Kennedy B.K. Regulation of yeast replicative life span by TOR and Sch9 in response to nutrients. Science 2005, 310:1193-1196.
74. Pan K.Z., Palter J.E., Rogers A.N., Olsen A., Chen D., Lithgow G.J., Kapahi P. Inhibition of mRNA translation extends lifespan in Caenorhabditis elegans. Aging Cell 2007, 6:111-119.
75. Powers R.W., Kaeberlein M., Caldwell S.D., Kennedy B.K., Fields S. Extension of chronological life span in yeast by decreased TOR pathway signaling. Genes Dev. 2006, 20:174-184.
76. Chen D., Thomas E.L., Kapahi P. HIF-1 modulates dietary restriction-mediated lifespan extension via IRE-1 in Caenorhabditis elegans. PLoS Genet. 2009, 5:e1000486.
77. Medvedik O., Lamming D.W., Kim K.D., Sinclair D.A. MSN2 and MSN4 link calorie restriction and TOR to sirtuin-mediated lifespan extension in Saccharomyces cerevisiae. PLoS Biol. 2007, 5:e261.
78. Sheaffer K.L., Updike D.L., Mango S.E. The Target of Rapamycin pathway antagonizes pha-4/FoxA to control development and aging. Curr. Biol. 2008, 18:1355-1364.
79. Patel P.H., Tamanoi F. Increased Rheb-TOR signaling enhances sensitivity of the whole organism to oxidative stress. J. Cell Sci. 2006, 119:4285-4292.
80. Budanov A.V., Karin M. p53 target genes sestrin1 and sestrin2 connect genotoxic stress and mTOR signaling. Cell 2008, 134:451-460.
81. Tettweiler G., Miron M., Jenkins M., Sonenberg N., Lasko P.F. Starvation and oxidative stress resistance in Drosophila are mediated through the eIF4E-binding protein, d4E-BP. Genes Dev. 2005, 19:1840-1843.
82. Teleman A.A., Chen Y.W., Cohen S.M. 4E-BP functions as a metabolic brake used under stress conditions but not during normal growth. Genes Dev. 2005, 19:1844-1848.
83. Lee J.H., Budanov A.V., Park E.J., Birse R., Kim T.E., Perkins G.A., Ocorr K., Ellisman M.H., Bodmer R., Bier E., Karin M. Sestrin as a feedback inhibitor of TOR that prevents age-related pathologies. Science 2010, 327:1223-1228.
84. Reiling J.H., Hafen E. The hypoxia-induced paralogs Scylla and Charybdis inhibit growth by down-regulating S6K activity upstream of TSC in Drosophila. Genes Dev. 2004, 18:2879-2892.
85. Cully M., Genevet A., Warne P., Treins C., Liu T., Bastien J., Baum B., Tapon N., Leevers S.J., Downward J. A role for p38 stress-activated protein kinase in regulation of cell growth via TORC1. Mol. Cell. Biol. 2010, 30:481-495.
86. Sonenberg N., Hershey J.W.B., Mathews B.M. In Translational Control of Gene Expression 2000, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York.
87. Ma X.M., Blenis J. Molecular mechanisms of mTOR-mediated translational control. Nat. Rev. Mol. Cell Biol. 2009, 10:307-318.
88. Selman C., Tullet J.M., Wieser D., Irvine E., Lingard S.J., Choudhury A.I., Claret M., Al-Qassab H., Carmignac D., Ramadani F., Woods A., Robinson I.C., Schuster E., Batterham R.L., Kozma S.C., Thomas G., Carling D., Okkenhaug K., Thornton J.M., Partridge L., Gems D., Withers D.J. Ribosomal protein S6 kinase 1 signaling regulates mammalian life span. Science 2009, 326:140-144.
89. Harrison D.E., Strong R., Sharp Z.D., Nelson J.F., Astle C.M., Flurkey K., Nadon N.L., Wilkinson J.E., Frenkel K., Carter C.S., Pahor M., Javors M.A., Fernandez E., Miller R.A. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 2009, 460:392-395.
90. Kaeberlein M., Kapahi P. Cell signaling. Aging is RSKy business. Science 2009, 326:55-56.
91. Kapahi P., Vijg J. Aging-lost in translation?. N. Engl. J. Med. 2009, 361:2669-2670.
92. Guertin D.A., Sabatini D.M. Defining the role of mTOR in cancer. Cancer Cell 2007, 12:9-22.
93. Grewal S.S., Evans J.R., Edgar B.A. Drosophila TIF-IA is required for ribosome synthesis and cell growth and is regulated by the TOR pathway. J. Cell Biol. 2007, 179:1105-1113.
94. Bell R., Hubbard A., Chettier R., Chen D., Miller J.P., Kapahi P., Tarnopolsky M., Sahasrabuhde S., Melov S., Hughes R.E. A human protein interaction network shows conservation of aging processes between human and invertebrate species. PLoS Genet. 2009, 5:e1000414.
95. Chen D., Pan K.Z., Palter J.E., Kapahi P. Longevity determined by developmental arrest genes in Caenorhabditis elegans. Aging Cell 2007, 6:525-533.
96. Curran S.P., Ruvkun G. Lifespan regulation by evolutionarily conserved genes essential for viability. PLoS Genet. 2007, 3:e56.
97. Hay N., Sonenberg N. Upstream and downstream of mTOR. Genes Dev. 2004, 18:1926-1945.
98. Tee A.R., Blenis J. mTOR, translational control and human disease. Semin. Cell Dev. Biol. 2005, 16:29-37.
99. Sonenberg N., Gingras A.C. The mRNA 5? cap-binding protein eIF4E and control of cell growth. Curr. Opin. Cell Biol. 1998, 10:268-275.
100. Marintchev A., Wagner G. Translation initiation: structures, mechanisms and evolution. Q. Rev. Biophys. 2004, 37:197-284.
101. Zid B.M., Rogers A.N., Katewa S.D., Vargas M.A., Kolipinski M.C., Lu T.A., Benzer S., Kapahi P. 4E-BP extends lifespan upon dietary restriction by enhancing mitochondrial activity in Drosophila. Cell 2009, 139:149-160.
102. Finch C.E. Longevity, Senescence, and the Genome 1990, University of Chicago Press, Chicago.
103. Henderson S.T., Bonafe M., Johnson T.E. daf-16 protects the nematode Caenorhabditis elegans during food deprivation. J. Gerontol. A Biol. Sci. Med. Sci. 2006, 61:444-460.
104. Steffen K.K., MacKay V.L., Kerr E.O., Tsuchiya M., Hu D., Fox L.A., Dang N., Johnston E.D., Oakes J.A., Tchao B.N., Pak D.N., Fields S., Kennedy B.K., Kaeberlein M. Yeast life span extension by depletion of 60S ribosomal subunits is mediated by Gcn4. Cell 2008, 133:292-302.
105. Syntichaki P., Troulinaki K., Tavernarakis N. eIF4E function in somatic cells modulates ageing in Caenorhabditis elegans. Nature 2007, 445:922-926.
106. Chippindale A.K., Leroi A.M., Kim S.B., Rose M.R. Phenotypic plasticity and selection in Drosophila life-history evolution. I. Nutrition and the cost of reproduction. J. Evol. Biol. 1993, 6:171-193.
107. Miller R.A., Buehner G., Chang Y., Harper J.M., Sigler R., Smith-Wheelock M. Methionine-deficient diet extends mouse lifespan, slows immune and lens aging, alters glucose, T4, IGF-I and insulin levels, and increases hepatocyte MIF levels and stress resistance. Aging Cell 2005, 4:119-125.
108. Orentreich N., Matias J.R., DeFelice A., Zimmerman J.A. Low methionine ingestion by rats extends life span. J. Nutr. 1993, 123:269-274.
109. Richie J.P., Leutzinger Y., Parthasarathy S., Malloy V., Orentreich N., Zimmerman J.A. Methionine restriction increases blood glutathione and longevity in F344 rats. FASEB J. 1994, 8:1302-1307.
110. Munro H.N. Evolution of protein metabolism in mammals. Mammalian Protein Metabolism 1969, vol. 3:133-182. H.N. Munro, J.B. Allison (Eds.).
111. Serikawa K.A., Xu X.L., MacKay V.L., Law G.L., Zong Q., Zhao L.P., Bumgarner R., Morris D.R. The transcriptome and its translation during recovery from cell cycle arrest in Saccharomyces cerevisiae. Mol. Cell. Proteomics 2003, 2:191-204.
112. Zong Q., Schummer M., Hood L., Morris D.R. Messenger RNA translation state: the second dimension of high-throughput expression screening. Proc. Natl Acad. Sci. USA 1999, 96:10632-10636.
113. Noda T., Ohsumi Y. Tor, a phosphatidylinositol kinase homologue, controls autophagy in yeast. J. Biol. Chem. 1998, 273:3963-3966.
114. Levine B., Klionsky D.J. Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev. Cell 2004, 6:463-477.
115. Scott R.C., Schuldiner O., Neufeld T.P. Role and regulation of starvation-induced autophagy in the Drosophila fat body. Dev. Cell 2004, 7:167-178.
116. Chang Y.Y., Neufeld T.P. An Atg1/Atg13 complex with multiple roles in TOR-mediated autophagy regulation. Mol. Biol. Cell 2009, 20:2004-2014.
117. Simonsen A., Cumming R.C., Brech A., Isakson P., Schubert D.R., Finley K.D. Promoting basal levels of autophagy in the nervous system enhances longevity and oxidant resistance in adult Drosophila. Autophagy 2008, 4:176-184.
118. Juhasz G., Erdi B., Sass M., Neufeld T.P. Atg7-dependent autophagy promotes neuronal health, stress tolerance, and longevity but is dispensable for metamorphosis in Drosophila. Genes Dev. 2007, 21:3061-3066.
119. Toth M.L., Sigmond T., Borsos E., Barna J., Erdelyi P., Takacs-Vellai K., Orosz L., Kovacs A.L., Csikos G., Sass M., Vellai T. Longevity pathways converge on autophagy genes to regulate life span in Caenorhabditis elegans. Autophagy 2008, 4:330-338.
120. Copeland J.M., Cho J., Lo T., Hur J.H., Bahadorani S., Arabyan T., Rabie J., Soh J., Walker D.W. Extension of Drosophila life span by RNAi of the mitochondrial respiratory chain. Curr. Biol. 2009, 19:1591-1598.
121. McCarroll S.A., Murphy C.T., Zou S., Pletcher S.D., Chin C.S., Jan Y.N., Kenyon C., Bargmann C.I., Li H. Comparing genomic expression patterns across species identifies shared transcriptional profile in aging. Nat. Genet. 2004, 36:197-204.
122. Dobrosotskaya I.Y., Seegmiller A.C., Brown M.S., Goldstein J.L., Rawson R.B. Regulation of SREBP processing and membrane lipid production by phospholipids in Drosophila. Science 2002, 296:879-883.
123. Seegmiller A.C., Dobrosotskaya I., Goldstein J.L., Ho Y.K., Brown M.S., Rawson R.B. The SREBP pathway in Drosophila: regulation by palmitate, not sterols. Dev. Cell 2002, 2:229-238.
124. Porstmann T., Santos C.R., Griffiths B., Cully M., Wu M., Leevers S., Griffiths J.R., Chung Y.L., Schulze A. SREBP activity is regulated by mTORC1 and contributes to Akt-dependent cell growth. Cell Metab. 2008, 8:224-236.
125. Ribeiro C., Dickson B.J. Sex peptide receptor and neuronal TOR/S6K signaling modulate nutrient balancing in Drosophila. Curr. Biol. 2010, 20:1000-1005.
126. Vargas M.A., Luo N., Yamaguchi A., Kapahi P. A role for S6 kinase and serotonin in postmating dietary switch and balance of nutrients in D. melanogaster. Curr. Biol. 2010, 20:1006-1011.
127. Lee K.P., Simpson S.J., Clissold F.J., Brooks R., Ballard J.W., Taylor P.W., Soran N., Raubenheimer D. Lifespan and reproduction in Drosophila: new insights from nutritional geometry. Proc. Natl Acad. Sci. USA 2008, 105:2498-2503.
128. Skorupa D.A., Dervisefendic A., Zwiener J., Pletcher S.D. Dietary composition specifies consumption, obesity, and lifespan in Drosophila melanogaster. Aging Cell 2008, 7:478-490.
129. Wu Q., Zhang Y., Xu J., Shen P. Regulation of hunger-driven behaviors by neural ribosomal S6 kinase in Drosophila. Proc. Natl Acad. Sci. USA 2005, 102:13289-13294.
130. Giebultowicz J., Kapahi P. Circadian clocks and metabolism: the nutrient-sensing AKT and TOR pathways make the link. Curr. Biol. 2010, 20:R608-R609.
131. Zheng X., Sehgal A. AKT and TOR signaling sets the circadian pacemaker. Curr. Biol. 2010, 20:1203-1208.
132. Berger Z., Ravikumar B., Menzies F.M., Oroz L.G., Underwood B.R., Pangalos M.N., Schmitt I., Wullner U., Evert B.O., O'Kane C.J., Rubinsztein D.C. Rapamycin alleviates toxicity of different aggregate-prone proteins. Hum. Mol. Genet. 2006, 15:433-442.
133. Ravikumar B., Vacher C., Berger Z., Davies J.E., Luo S., Oroz L.G., Scaravilli F., Easton D.F., Duden R., O'Kane C.J., Rubinsztein D.C. Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease. Nat. Genet. 2004, 36:585-595.
134. Khurana V., Lu Y., Steinhilb M.L., Oldham S., Shulman J.M., Feany M.B. TOR-mediated cell-cycle activation causes neurodegeneration in a Drosophila tauopathy model. Curr. Biol. 2006, 16:230-241.
135. Wang T., Lao U., Edgar B.A. TOR-mediated autophagy regulates cell death in Drosophila neurodegenerative disease. J. Cell Biol. 2009, 186:703-711.
136. Tain L.S., Mortiboys H., Tao R.N., Ziviani E., Bandmann O., Whitworth A.J. Rapamycin activation of 4E-BP prevents parkinsonian dopaminergic neuron loss. Nat. Neurosci. 2009, 12:1129-1135.
137. Wessells R., Fitzgerald E., Piazza N., Ocorr K., Morley S., Davies C., Lim H.Y., Elmen L., Hayes M., Oldham S., Bodmer R. d4eBP acts downstream of both dTOR and dFoxo to modulate cardiac functional aging in Drosophila. Aging Cell 2009, 8:542-552.