Molecular mechanisms of aging and immune system regulation in Drosophila

International Journal of Molecular Sciences

Volumn 13, Issue 8, 2012, Pages 9826-9844

  Eleftherianos, Ioannis ^a   Castillo, Julio Cesar ^a  

^a GEORGE WASHINGTON UNIVERSITY   (United States)

Author keywords

Age related diseases; Aging; Antimicrobial peptides; Gene transcription; Infection; Innate immunity; Insects

Indexed keywords

HEAT SHOCK PROTEIN; SILENT INFORMATION REGULATOR PROTEIN 2; STRESS ACTIVATED PROTEIN KINASE; TARGET OF RAPAMYCIN KINASE; TRANSCRIPTION FACTOR FOXO;

AGING; DROSOPHILA MELANOGASTER; GENETICS; GENOMICS; IMMUNOREGULATION; INNATE IMMUNITY; LIFESPAN; MOLECULAR BIOLOGY; MOLECULAR MECHANISM; NONHUMAN; REVIEW; SIGNAL TRANSDUCTION; ANIMAL; DROSOPHILA; HUMAN; IMMUNE SYSTEM; IMMUNOLOGY; PHYSIOLOGY;

AGING; ANIMALS; DROSOPHILA; HUMANS; IMMUNE SYSTEM; SIGNAL TRANSDUCTION;

EID: 84865013231     PISSN: 16616596     EISSN: 14220067     Source Type: Journal    
DOI: 10.3390/ijms13089826     Document Type: Review

References (123)

1. Kenyon, C.J. The genetics of ageing. Nature 2010, 464, 504-512.
2. Paaby, A.; Schmidt, P. Dissecting the genetics of longevity in Drosophila melanogaster. Fly 2009, 3, 29-38.
3. Ackermann, M.; Chao, L.; Bergstrom, C.T.; Doebeli, M. On the evolutionary origin of aging. Aging Cell 2007, 6, 235-244.
4. Akira, S.; Uematsu, S.; Takeuchi, O. Pathogen recognition and innate immunity. Cell 2006, 124, 783-801.
5. Takeuchi, O.; Akira, S. Signaling pathways activated by microorganisms. Curr. Opin. Cell Biol. 2007, 19, 185-191.
6. Ferrandon, D.; Imler, J.L.; Hetru, C.; Hoffmann, J. The Drosophila systemic immune response: Sensing and signalling during bacterial and fungal infections. Nat. Rev. Immunol. 2007, 7, 862- 874.
7. DeVeale, B.; Brummel, T.; Seroude, L. Immunity and aging: The enemy within? Aging Cell 2004, 3, 195-208.
8. Alper, S. Model systems to the rescue: The relationship between aging and innate immunity. Commun. Integr. Biol. 2010, 3, 409-414.
9. Feldhaar, H.; Gross, R. Immune reactions of insects on bacterial pathogens and mutualists. Microbes Infect. 2008, 10, 1082-1088.
10. Pursall, E.R.; Rolff, J. Immune responses accelerate ageing: Proof-of-principle in an insect model. PLoS One 2011, 6, e19972.
11. Schneider, D.S. Using Drosophila as a model insect. Nat. Rev. Genet. 2000, 1, 218-226.
12. Grotewiel, M.S.; Martin, I.; Bhandari, P.; Cook-Wiens, E. Functional senescence in Drosophila melanogaster. Ageing Res. Rev. 2005, 4, 372-397.
13. Cho, J.; Hur, J.H.; Walker, D.W. The role of mitochondria in Drosophila aging. Exp. Gerontol. 2011, 46, 331-334.
14. Katewa, D.; Kapahi, P. Role of TOR signaling in aging and related biological processes in Drosophila melanogaster. Exp. Gerontol. 2012, 45, 382-390.
15. Inoki, K.; Guan, K.L. Complexity of the TOR signaling network. Trends Cell Biol. 2006, 16, 206-212.
16. 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.
17. 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.
18. 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.
19. 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.
20. 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.
21. 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., et al. Sestrin as a feedback inhibitor of TOR that prevents age-related pathologies. Science 2010, 327, 1223-1228.
22. Giannakou, M.E.; Partridge, L. Role of insulin-like signaling in Drosophila lifespan. Trends Biochem. Sci. 2007, 32, 180-188.
23. Partridge, L.; Alic, N.; Bjedov, I.; Piper, M.D.W. Ageing in Drosophila: The role of the insulin/Igf and TOR signaling network. Exp. Gerontol. 2011, 46, 376-381.
24. Gronke, S.; Clarke, D.F.; Broughton, S.; Andrews, T.D.; Partridge, L. Molecular evolution and functional characterization of Drosophila insulin-like peptides. PLoS Genet. 2010, 6, e1000857.
25. Tatar, M.; Kopelman, A.; Epstein, D.; Tu, M.P.; Yin, C.M.; Garofalo, R.S. A mutant Drosophila insulin receptor homolog that extends life-span and impairs neuroendocrine function. Science 2001, 292, 107-110.
26. Clancy, D.J.; Gems, D.; Harshman, L.G.; Oldham, S.; Stocker, H.; Hafen, E.; Leevers, S.J.; Partridge, L. Extension of life-span by loss of CHICO, a Drosophila insulin receptor substrate protein. Science 2001, 292, 104-106.
27. Slack, C.; Werz, C.; Wieser, D.; Alic, N.; Foley, A.; Stocker, H.; Withers, D.J.; Thornton, J.M.; Hafen, E.; Partridge, L. Regulation of lifespan, metabolism, and stress responses by the Drosophila SH2B protein, Lnk. PLoS Genet. 2010, 6, e1000881.
28. Piper, M.D.; Selman, C.; McElwee, J.J.; Partridge, L. Separating cause from effect: How does insulin/IGF signalling control lifespan in worms, flies and mice? J. Intern. Med. 2008, 263, 179-191.
29. McElwee, J.J.; Schuster, E.; Blanc, E.; Piper, M.D.; Thomas, J.H.; Patel, D.S.; Selman, C.; Withers, D.J.; Thornton, J.M.; Partridge, L., et al. Evolutionary conservation of regulated longevity assurance mechanisms. Genome Biol. 2007, 8, R132.
30. Min, K.J.; Yamamoto, R.; Buch, S.; Pankratz, M.; Tatar, M. Drosophila lifespan control by dietary restriction independent of insulin-like signaling. Aging Cell 2008, 7, 199-206.
31. Mair, W.; Dillin, A. Aging and survival: The genetics of life span extension by dietary restriction. Annu. Rev. Biochem. 2008, 77, 727-754.
32. 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.
33. Giannakou, M.E.; Goss, M.; Partridge, L. Role of dFOXO in lifespan extension by dietary restriction in Drosophila melanogaster: Not required, but its activity modulates the response. Aging Cell 2008, 7, 187-198.
34. Flatt, T. Survival costs of reproduction in Drosophila. Exp. Gerontol. 2011, 46, 369-375.
35. Nishimura, M.; Ocorr, K.; Bodmer, R.; Cartry, J. Drosophila as a model to study cardiac aging. Exp. Gerontol. 2011, 46, 326-330.
36. Jones, M.A.; Grotewiel, M. Drosophila as a model for age-related impairment in locomotor and other behaviors. Exp. Gerontol. 2011, 46, 320-325.
37. Bonner, J.M.; Boulianne, G.L. Drosophila as a model to study age-related neurodegenerative disorders: Alzheimer's disease. Exp. Gerontol. 2011, 46, 335-339.
38. Lin, Y.-J.; Seroude, L.; Benzer, S. Extended life-span and stress resistance in the Drosophila mutant methuselah. Science 1998, 282, 943-946.
39. Cvejic, S.; Zhu, Z.; Felice, S.J.; Berman, Y.; Huang, X.-Y. The endogenous ligand Stunted of the GPCR Methuselah extends lifespan in Drosophila. Nat. Cell Biol. 2004, 6, 540-546.
40. Kidd, T.; Abu-Shumays, R.; Katzen, A.; Sisson, J.C.; Jiménez, G.; Pinchin, S.; Sullivan, W.; Ish-Horowicz, D. The epsilon-subunit of mitochondrial ATP synthase is required for normal spindle orientation during the Drosophila embryonic divisions. Genetics 2005, 170, 697-708.
41. Rogina, B.; Reenan, R.A.; Nilsen, S.P.; Helfand, S.L. Extended life-span conferred by cotransporter gene mutation in Drosophila. Science 2000, 290, 2137-2140.
42. Toivonen, J.M.; Walker, G.A.; Martinez-Diaz, P.; Bjedov, I.; Driege, Y.; Jacobs, H.T.; Gems, D.; Partridge, L. No influence of Indy on lifespan in Drosophila after correction for genetic and cytoplasmic background effect. PLOS Genet. 2007, 3, 95.
43. North, B.J.; Verdin, E. Sirtuins: Sir2-related NAD-dependent protein deacetylases. Genome Biol. 2004, 5, 224.
44. Longo, V.D.; Kennedy, B.K. Sirtuins in aging and age-related disease. Cell 2006, 126, 257-268.
45. Parsons, X.H.; Garcia, S.N.; Pillus, L.; Kadonaga, J.T. Histone deacetylation by Sir2 generates a transcriptionally repressed nucleoprotein complex. Proc. Natl. Acad. Sci. USA 2003, 100, 1609-1614.
46. Frankel, S.; Ziafazeli, T.; Rogina, B. dSir2 and longevity in Drosophila. Exp. Gerontol. 2012, 46, 391-396.
47. Rogina, B.; Helfand, S.L. Sir2 mediates longevity in the fly through a pathway related to calorie restriction. Proc. Natl. Acad. Sci. USA 2004, 101, 15998-16003.
48. Rogina, B.; Helfand, S.L.; Frankel, S. Longevity regulation by Drosophila Rpd3 deacetylase and caloric restriction. Science 2002, 298, 1745.
49. Bunett, G.; Valentini, S.; Cabreiro, F.; Goss, M.; Somogyvari, M.; Piper, M.D.; Hoddinott, M.; Sutphin, G.L.; Leko, V.; McElwee, J.J., et al. Absence of effects of Sir2 overxpression on lifespan in C. elegans and Drosophila. Nature 2011, 477, 482-485.
50. Reinhardt, H.C.; Schumacher, B. The p53 network: Cellular and systemic DNA damage responses in aging and cancer. Trends Genet. 2012, 28, 128-136.
51. Rutkowski, R.; Hofmann, K.; Gartner, A. Phylogeny and function of the invertebrate p53 superfamily. Cold Spring Harb. Perspect. Biol. 2010, 2, a001131.
52. Levine, A.J.; Feng, Z.; Mak, T.W.; You, H.; Jin, S. Coordination and communication of between the p53 and IGF-1-AKT-TOR signal transduction pathways. Genes Dev. 2006, 20, 267-275.
53. Donehower, L.A.; Levine, A.J. P53, Cancer, and Longevity. In Molecular Biology of Aging; Guarente, L.P., Partridge, L., Wallace, D.C., Eds.; Cold Spring Harbor Laboratory Press: New York, NY, USA, 2008; pp. 127-152.
54. Bauer, J.H.; Poon, P.C.; Glatt-Deeley, H.; Abrams, J.M.; Helfand, S.L. Neuronal expression of p53 dominant-negative proteins in adult Drosophila melanogaster extends life span. Curr. Biol. 2005, 15, 2063-2068.
55. Bauer, J.H.; Chang, C.; Morris, S.N.; Hozier, S.; Andersen, S.; Waitzman, J.S.; Helfand, S.L. Expression of dominant-negative Dmp53 in the adult fly brain inhibits insulin signaling. Proc. Natl. Acad. Sci. USA 2007, 104, 13355-13360.
56. Weston, C.R.; Davis, R.J. The JNK signal transduction pathway. Curr. Opin. Genet. Dev. 2002, 12, 14-21.
57. Park, J.M.; Brady, H.; Ruocco, M.G.; Sun, H.; Williams, D.; Lee, S.J.; Kato, T., Jr.; Richards, N.; Chan, K.; Mercurio, F., et al. Targeting of TAK1 by the NF-κB protein Relish regulates the JNK-mediated immune response in Drosophila. Genes Dev. 2004, 18, 584-594.
58. Davis, R.J. Signal transduction by the JNK group of MAP kinases. Cell 2000, 103, 239-252.
59. Biteau, B.; Karpac, J.; Hwangbo, D.S.; Jasper, H. Regulation of Drosophila lifespan by JNK signaling. Exp. Gerontol. 2012, 46, 349-354.
60. Wang, M.C.; Bohmann, D.; Jasper, H. JNK signaling confers tolerance to oxidative stress and extends lifespan in Drosophila. Dev. Cell 2003, 5, 811-816.
61. Wang, M.C.; Bohmann, D.; Jasper, H. JNK extends life span and limits growth by antagonizing cellular and organism-wide responses to insulin signaling. Cell 2005, 121, 115-125.
62. Karpac, J.; Jasper, H. Insulin and JNK: Optimizing metabolic homeostasis and lifespan. Trends Endocrinol. Metab. 2009, 20, 100-106.
63. Garrido, C.; Paul, C.; Seigneuric, R.; Kampinga, H.H. The small heat shock proteins family: The long forgotten chaperones. Int. J. Biochem. Cell Biol. 2012, doi:10.1016/j.biocel.2012.02.022.
64. Tower, J. Heat shock proteins and Drosophila aging. Exp. Gerontol. 2011, 46, 355-362.
65. Tatar, M.; Khazaeli, A.A.; Curtsinger, J.W. Chaperoning extended life. Nature 1997, 390, 30.
66. Minois, N.; Khazaeli, A.A.; Curtsinger, J.W. Locomotor activity as a function of age and life span in Drosophila melanogaster overexpressing hsp70. Exp. Gerontol. 2001, 36, 1137-1153.
67. Wang, H.D.; Kazemi-Esfarjani, P.; Benzer, S. Multiple-stress analysis for isolation of Drosophila longevity genes. Proc. Natl. Acad. Sci. USA 2004, 101, 12610-12615.
68. Morrow, G.; Samson, M.; Michaud, S.; Tanguay, R.M. Over expression of the small mitochondrial Hsp22 extends Drosophila life span and increases resistance to oxidative stress. FASEB J. 2004, 18, 598-599.
69. Cuervo, A.M. Autophagy and aging: Keeping that old broom working. Trends Genet. 2008, 24, 604-612.
70. Madeo, F.; Tavernarakis, N.; Kroemer, G. Can autophagy promote longevity? Nat. Cell Biol. 2010, 12, 842-846.
71. Juhasz, G.; Erdi, B.; 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.
72. 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.
73. Simonsen, A.; Cumming, R.C.; Finley, K.D. Linking lysosomal trafficking defects with changes in aging and stress response in Drosophila. Autophagy 2007, 3, 499-501.
74. Madeo, F.; Eisenberg, T.; Buttner, S.; Ruckenstuhl, C.; Kroemer, G. Spermidine: A novel autophagy inducer and longevity elixir. Autophagy 2010, 6, 160-162.
75. Ferrandon, D.; Imler, J.L.; Hetru, C.; Hoffmann, J. The Drosophila systemic immune response: Sensing and signalling during bacterial and fungal infections. Nat. Rev. Immunol. 2007, 7, 862- 874.
76. Dionne, M.S.; Schneider, D.S. Models of infectious diseases in the fruit fly Drosophila melanogaster. Dis. Models Mech. 2008, 1, 43-49.
77. Kurata, S. Fly immunity: Recognition of pathogens and induction of immune responses. Adv. Exp. Med. Biol. 2010, 708, 205-217.
78. Lemaitre, B.; Hoffmann, J. The host defense of Drosophila melanogaster. Annu. Rev. Immunol 2007, 25, 697-743.
79. Hetru, C.; Hoffmann, J.A. NF-κB in the immune response of Drosophila. Cold Spring Harb. Perspect. Biol. 2009, 1, a000232.
80. Hultmark, D. Drosophila immunity: Paths and patterns. Curr. Opin. Immunol. 2003, 15, 12-19.
81. Marek, L.R.; Kagan, J.C. Phosphoinositide binding by the Toll adaptor dMyD88 controls antibacterial responses in Drosophila. Immunity 2012, 36, 612-622.
82. Valanne, S.; Wang, J.H.; Rämet, M. The Drosophila Toll signaling pathway. J. Immunol. 2011, 186, 649-656.
83. Leulier, F.; Lemaitre, B. Toll-like receptors-Taking an evolutionary approach. Nat. Rev. Genet. 2008, 9, 165-178.
84. Rämet, M. The fruit fly Drosophila melanogaster unfolds the secrets of innate immunity. Acta Paediatr. 2012, 101, 900-905.
85. Hoffmann, J.A.; Reichhart, J.-M. Drosophila innate immunity: An evolutionary perspective. Nat. Immunol. 2002, 3, 121-126.
86. Georgel, P.; Naitza, S.; Kappler, C.; Ferrandon, D.; Zachary, D.; Swimmer, C.; Kopczynski, C.; Duyk, G.; Reichhart, J.M.; Hoffmann, J.A. Drosophila immune deficiency (IMD) is a death domain protein that activates antibacterial defense and can promote apoptosis. Dev. Cell 2001, 1, 503-514.
87. Ganesan, S.; Aggarwal, K.; Paquette, N.; Silverman, N. NF-κB/Rel proteins and the humoral immune responses of Drosophila melanogaster. Curr. Top. Microbiol. Immunol. 2011, 349, 25-60.
88. Broderick, N.A.; Welchman, D.P.; Lemaitre, B. Recognition and response to microbial infection in Drosophila. In Insect Infection and Immunity: Evolution, Ecology, and Mechanisms; Rolff, R., Ed.; Oxford University Press: Oxford, UK, 2009; pp. 16-33.
89. Uvell, H.; Engstrom, Y.A. Multilayered defense against infection: Combinatorial control of insect immune genes. Trends Genet. 2007, 23, 342-349
90. Aggarwal, K.; Silverman, N. Positive and negative regulation of the Drosophila immune response. BMB Rep. 2008, 41, 267-277.
91. Zerofsky, M.; Harel, E.; Silverman, N.; Tatar, M. Aging of the innate immune response in Drosophila melanogaster. Aging Cell 2005, 4, 103-108.
92. Landis, G.N.; Abdueva, D.; Skvortsov, D.; Yang, J.; Rabin, B.E.; Carrick, J.; Tavare, S.; Tower, J. Similar gene expression patterns characterize aging and oxidative stress in Drosophila melanogaster. Proc. Natl. Acad. Sci. USA 2004, 101, 7663-7668.
93. Moskalev, A.; Shaposhnikov, M. Pharmacological inhibition of NF-κB prolongs lifespan of Drosophila melanogaster. Aging 2011, 3, 391-394.
94. Pletcher, S.D.; Macdonald, S.J.; Marguerie, R.; Certa, U.; Stearns, S.C.; Goldstein, D.B.; Partridge, L. Genome-wide transcript profiles in aging and calorically restricted Drosophila melanogaster. Curr. Biol. 2002, 12, 712-723.
95. Seroude, L.; Brummel, T.; Kapahi, P.; Benzer, S. Spatio-temporal analysis of gene expression during aging in Drosophila melanogaster. Aging Cell 2002, 1, 47-56.
96. Kim, H.; Kim, J.; Lee, Y.; Yang, J.; Han, K. Transcriptional regulation of the Methuselah gene by Dorsal protein in Drosophila melanogaster. Mol. Cell 2006, 21, 261-268.
97. Schneider, D.S.; Ayres, J.S. Two ways to survive infection: What resistance and tolerance can teach us about treating infectious diseases. Nat. Rev. Immunol. 2008, 8, 889-895.
98. Kim, Y.S.; Nam, H.J.; Chung, H.Y.; Kim, N.D.; Ryu, J.H.; Lee, W.J.; Arking, R.; Yoo, M.A. Role of xanthine dehydrogenase and aging on the innate immune response of Drosophila. Age (Omaha) 2001, 24, 187-193.
99. Libert, S.; Chao, Y.; Chu, X.; Pletcher, S.D. Trade-offs between longevity and pathogen resistance in Drosophila melanogaster are mediated by NF-κB signaling. Aging Cell 2006, 5, 533-543.
100. Min, K.T.; Benzer, S. Wolbachia, normally a symbiont of Drosophila, can be virulent, causing degeneration and early death. Proc. Natl. Acad. Sci. USA 1997, 94, 10792-10796.
101. Fry, A.J.; Rand, D.M. Wolbachia interactions that determine Drosophila melanogaster survival. Evolution 2002, 56, 1976-1981.
102. Siozios, S.; Sapountzis, P.; Ioannidis, P.; Bourtzis, K. Wolbachia symbiosis and insect immune response. Insect Sci. 2008, 15, 89-100.
103. Brummel, T.; Ching, A.; Seroude, L.; Simon, A.F.; Benzer, S. Drosophila lifespan enhancement by exogenous bacteria. Proc. Natl. Acad. Sci. USA 2004, 101, 12974-12979.
104. Ren, C.; Webster, P.; Finkel, S.E.; Tower, J. Increased internal and external bacterial load during Drosophila aging without life-span trade-off. Cell Metab. 2007, 6, 144-152.
105. Ramsden, S.; Cheung, Y.Y.; Seroude, L. Functional analysis of the Drosophila immune response during aging. Aging Cell 2008, 7, 225-236.
106. Le Bourg, E. Combined effects of suppressing live yeast and of a cold pretreatment on longevity, aging and resistance to several stresses in Drosophila melanogaster. Biogerontology 2010, 11, 245-254.
107. Le Bourg, E.; Massou, I.; Gobert, V. Cold stress increases resistance to fungal infection throughout life in Drosophila melanogaster. Biogerontology 2009, 10, 613-625.
108. Fauvarque, M.O.; Williams M.J. Drosophila cellular immunity: A story of migration and adhesion. J. Cell Sci. 2011, 124, 1373-1382.
109. Mackenzie, D.K.; Bussiere, L.F.; Tinsley, M.C. Senescence of the cellular immune response in Drosophila melanogaster. Exp. Gerontol. 2011, 46, 853-859.
110. Libert, S.; Chao, Y.; Zwiener, J.; Pletcher, S.D. Realized immune response is enhanced in long- lived puc and chico mutants but is unaffected by dietary restriction. Aging Cell 2008, 45, 810-817.
111. Becker, T.; Loch, G.; Beyer, M.; Zinke, I.; Aschenbrenner A.C.; Carrera, P.; Inhester, T.; Schultze, J.L.; Hoch, M. FOXO-dependent regulation of innate immune homeostasis. Nature 2010, 463, 369-373.
112. DiAngelo, J.R.; Bland, M.L.; Bambina, S.; Cherry, S.; Birnbaum, M.J. The immune response attenuates growth and nutrient storage in Drosophila by reducing insulin signaling. Proc. Natl. Acad. Sci. USA 2009, 106, 20853-20858.
113. Lesser, K.J.; Paiusi, I.C.; Leips, J. Naturally occurring genetic variation in the age-specific immune response of Drosophila melanogaster. Aging Cell 2006, 5, 293-295.
114. Cho, I.; Horn, L.; Felix, T.M.; Foster, L.; Gwendlyn, G.; Starz-Gaiano, M.; Chambers, M.M.; de Luca, M.; Leips, J. Age-and diet-specific effects on variation at S6 kinase on life history, metabolic, and immune response traits in Drosophila melanogaster. DNA Cell Biol. 2010, 29, 473-485.
115. Felix, T.M.; Hughes, K.A.; Stone, E.A.; Drnevich, J.M.; Leips, J. Age-specific variation in immune response in Drosophila melanogaster has a genetic basis. Genetics 2012, doi:10.1534/genetics.112.14064.
116. Ren, C.; Finkel, S.E.; Tower, J. Conditional inhibition of autophagy genes in adult Drosophila impairs immunity without compromising longevity. Exp. Gerontol. 2009, 44, 228-235.
117. Croker, B.; Crozat, K.; Berger, M.; Xia, Y.; Sovath, S.; Schaffer, L.; Eleftherianos, I.; Imler, J.L.; Beutler, B. ATP-sensitive potassium channels mediate survival during infection in mammals and insects. Nat. Genet. 2007, 39, 1453-1460.
118. Eleftherianos, I.; Won, S.; Chtarbanova, S.; Squiban, B.; Ocorr, K.; Bodmer R.; Beutler, B.; Hoffmann, J.A.; Imler, J.A. ATP-sensitive potassium channel (KATP)-dependent regulation of cardiotropic viral infections. Proc. Natl. Acad. Sci. USA 2011, 108, 12024-12029.
119. Akasaka, T.; Klinedinst, S.; Ocorr, K.; Bustamante, E.L.; Kim, S.K.; Bodmer, R. The ATP-sensitive potassium (KATP) channel-encoded dSUR gene is required for Drosophila heart function and is regulated by Tinman. Proc. Natl. Acad. Sci. USA 2006, 103, 11999-12004.
120. Burger, J.M.; Promislow, D.E. Sex-specific effects of interventions that extend fly life span. Sci. Aging Knowl. Environ. 2004, 2004, p e30.
121. Taylor, K.; Kimbrell, D.A. Host immune response and differential survival of the sexes in Drosophila. Fly 2007, 1, 197-204.
122. Shirazu-Hiza, M.M.; Schneider, D.S. Confronting physiology: How do infected flies die? Cell. Microbiol. 2007, 9, 2775-2783.
123. Alper, S. Model systems to the rescue: The relationship between aging and innate immunity. Commun. Integr. Biol. 2010, 3, 409-414.