Model systems to the rescue

References

• Gomez CR, Nomellini V, Faunce DE, Kovacs EJ. Innate immunity and aging. Exp Gerontol 2008; 43:718 - 728
   PubMed Web of Science ®Google Scholar
• Weiskopf D, Weinberger B, Grubeck-Loebenstein B. The aging of the immune system. Transpl Int 2009; 22:1041 - 1050
   PubMed Web of Science ®Google Scholar
• Franceschi C, Bonafe M, Valensin S, Olivieri F, De Luca M, Ottaviani E, et al. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci 2000; 908:244 - 254
   PubMed Web of Science ®Google Scholar
• Wood WB. The Nematode Caenorhabditis elegans 1988; New York Cold Spring Harbor Laboratory Press
   Google Scholar
• Kenyon CJ. The genetics of ageing. Nature 2010; 464:504 - 512
   PubMed Web of Science ®Google Scholar
• Friedman DB, Johnson TE. A mutation in the age-1 gene in Caenorhabditis elegans lengthens life and reduces hermaphrodite fertility. Genetics 1988; 118:75 - 86
   PubMed Web of Science ®Google Scholar
• 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 - 464
   PubMed Web of Science ®Google Scholar
• Klass MR. A method for the isolation of longevity mutants in the nematode Caenorhabditis elegans and initial results. Mech Ageing Dev 1983; 22:279 - 286
   PubMed Web of Science ®Google Scholar
• Barsyte D, Lovejoy DA, Lithgow GJ. Longevity and heavy metal resistance in daf-2 and age-1 long-lived mutants of Caenorhabditis elegans. Faseb J 2001; 15:627 - 634
   PubMed Web of Science ®Google Scholar
• Gems D, Sutton AJ, Sundermeyer ML, Albert PS, King KV, Edgley ML, et al. Two pleiotropic classes of daf-2 mutation affect larval arrest, adult behavior, reproduction and longevity in Caenorhabditis elegans. Genetics 1998; 150:129 - 155
   PubMed Web of Science ®Google Scholar
• Giannakou MEPL. Role of insulin-like signalling in Drosophila lifespan. Trends Biochem Sci 2007; 32:180 - 188
   PubMedGoogle Scholar
• Honda Y, Honda S. Oxidative stress and life span determination in the nematode Caenorhabditis elegans. Ann N Y Acad Sci 2002; 959:466 - 474
   PubMed Web of Science ®Google Scholar
• Hyun M, Lee J, Lee K, May A, Bohr VA, Ahn B. Longevity and resistance to stress correlate with DNA repair capacity in Caenorhabditis elegans. Nucleic Acids Res 2008; 36:1380 - 1389
   Google Scholar
• Larsen PL. Aging and resistance to oxidative damage in Caenorhabditis elegans. Proc Natl Acad Sci USA 1993; 90:8905 - 8909
   PubMed Web of Science ®Google Scholar
• Lithgow GJ, White TM, Melov S, Johnson TE. Thermotolerance and extended life-span conferred by single-gene mutations and induced by thermal stress. Proc Natl Acad Sci USA 1995; 92:7540 - 7544
   PubMed Web of Science ®Google Scholar
• Murakami S, Johnson TE. A genetic pathway conferring life extension and resistance to UV stress in Caenorhabditis elegans. Genetics 1996; 143:1207 - 1218
   PubMed Web of Science ®Google Scholar
• Vanfleteren JR. Oxidative stress and ageing in Caenorhabditis elegans. Biochem J 1993; 292:605 - 608
   PubMed Web of Science ®Google Scholar
• Garsin DA, Villanueva JM, Begun J, Kim DH, Sifri CD, Calderwood SB, et al. Long-lived C. elegans daf-2 mutants are resistant to bacterial pathogens. Science 2003; 300:1921
   PubMed Web of Science ®Google Scholar
• Arantes-Oliveira N, Apfeld J, Dillin A, Kenyon C. Regulation of life-span by germ-line stem cells in Caenorhabditis elegans. Science 2002; 295:502 - 505
   PubMed Web of Science ®Google Scholar
• Hsin HKC. Signals from the reproductive system regulate the lifespan of C. elegans. Nature 1999; 399:362 - 366
   PubMed Web of Science ®Google Scholar
• Alper S, McElwee M, Apfeld J, Lackford B, Freedman J, Schwartz D. The Caenorhabditis elegans germ line regulates distinct signaling pathways to control lifespan and innate immunity. J Biol Chem 2010; 285:1822 - 1828
   PubMed Web of Science ®Google Scholar
• Evans E, Chen W, Tan M. The DAF-2 Insulin-like Signaling Pathway Independently Regulates Aging and Innate Immunity in C. elegans. Aging Cell 2008; 7:879 - 893
   PubMed Web of Science ®Google Scholar
• Miyata S, Begun J, Troemel ER, Ausubel FM. DAF-16-dependent suppression of immunity during reproduction in Caenorhabditis elegans. Genetics 2008; 178:903 - 918
   Google Scholar
• Baumeister R, Schaffitzel E, Hertweck M. Endocrine signaling in Caenorhabditis elegans controls stress response and longevity. J Endocrinol 2006; 190:191 - 202
   PubMed Web of Science ®Google Scholar
• Panowski SH, Dillin A. Signals of youth: endocrine regulation of aging in Caenorhabditis elegans. Trends Endocrinol Metab 2009; 20:259 - 264
   PubMed Web of Science ®Google Scholar
• Russell SJKC. Endocrine regulation of ageing. Nat Rev Mol Cell Biol 2007; 8:681 - 691
   PubMed Web of Science ®Google Scholar
• Wolff S, Dillin A. The trifecta of aging in Caenorhabditis elegans. Exp Gerontol 2006; 41:894 - 903
   Google Scholar
• Kimura KD, Tissenbaum HA, Liu Y, Ruvkun G. daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans. Science 1997; 277:942 - 946
   PubMed Web of Science ®Google Scholar
• Li W, Kennedy SG, Ruvkun G. 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 2003; 17:844 - 858
   Google Scholar
• Pierce SB, Costa M, Wisotzkey R, Devadhar S, Homburger SA, Buchman AR, et al. 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 2001; 15:672 - 686
   PubMed Web of Science ®Google Scholar
• Morris JZ, Tissenbaum HA, Ruvkun G. A phosphatidylinositol-3-OH kinase family member regulating longevity and diapause in Caenorhabditis elegans. Nature 1996; 382:536 - 539
   PubMed Web of Science ®Google Scholar
• Hertweck M, Gobel C, Baumeister R. C. elegans SGK-1 is the critical component in the Akt/PKB kinase complex to control stress response and life span. Dev Cell 2004; 6:577 - 588
   PubMed Web of Science ®Google Scholar
• Paradis S, Ailion M, Toker A, Thomas JH, Ruvkun G. A PDK1 homolog is necessary and sufficient to transduce AGE-1 PI3 kinase signals that regulate diapause in Caenorhabditis elegans. Genes Dev 1999; 13:1438 - 1452
   PubMedGoogle Scholar
• Paradis S, Ruvkun G. Caenorhabditis elegans Akt/PKB transduces insulin receptor-like signals from AGE-1 PI3 kinase to the DAF-16 transcription factor. Genes Dev 1998; 12:2488 - 2498
   PubMed Web of Science ®Google Scholar
• Lee RY, Hench J, Ruvkun G. Regulation of C. elegans DAF-16 and its human ortholog FKHRL1 by the daf-2 insulin-like signaling pathway. Curr Biol 2001; 11:1950 - 1957
   PubMed Web of Science ®Google Scholar
• Lin K, Dorman JB, Rodan A, Kenyon C. daf-16: An HNF-3/forkhead family member that can function to double the life-span of Caenorhabditis elegans. Science 1997; 278:1319 - 1322
   PubMed Web of Science ®Google Scholar
• Lin KHH, Libina N, Kenyon C. Regulation of the Caenorhabditis elegans longevity protein DAF-16 by insulin/IGF-1 and germline signaling. Nat Genet 2001; 28:139 - 145
   PubMed Web of Science ®Google Scholar
• Ogg S, Paradis S, Gottlieb S, Patterson GI, Lee L, Tissenbaum HA, et al. The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans. Nature 1997; 389:994 - 999
   PubMed Web of Science ®Google Scholar
• McElwee J, Bubb K, Thomas JH. Transcriptional outputs of the Caenorhabditis elegans forkhead protein DAF-16. Aging Cell 2003; 2:111 - 121
   PubMed Web of Science ®Google Scholar
• Murphy CT, McCarroll SA, Bargmann CI, Fraser A, Kamath RS, Ahringer J, et al. Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans. Nature 2003; 424:277 - 283
   PubMed Web of Science ®Google Scholar
• Ogg S, Ruvkun G. The C. elegans PTEN homolog, DAF-18, acts in the insulin receptor-like metabolic signaling pathway. Mol Cell 1998; 2:887 - 893
   PubMed Web of Science ®Google Scholar
• Berman JRKC. Germ-cell loss extends C. elegans life span through regulation of DAF-16 by kri-1 and lipophilic-hormone signaling. Cell 2006; 124:1055 - 1068
   Google Scholar
• Fares H, Greenwald I. Genetic analysis of endocytosis in Caenorhabditis elegans: coelomocyte uptake defective mutants. Genetics 2001; 159:133 - 145
   Google Scholar
• Alper S, McBride SJ, Lackford B, Freedman JH, Schwartz DA. Specificity and complexity of the C. elegans innate immune response. Mol Cell Biol 2007; 27:5544 - 5553
   PubMed Web of Science ®Google Scholar
• Couillault C, Pujol N, Reboul J, Sabatier L, Guichou JF, Kohara Y, et al. TLR-independent control of innate immunity in Caenorhabditis elegans by the TIR domain adaptor protein TIR-1, an ortholog of human SARM. Nat Immunol 2004; 5:488 - 494
   PubMed Web of Science ®Google Scholar
• Liberati NT, Fitzgerald KA, Kim DH, Feinbaum R, Golenbock DT, Ausubel FM. Requirement for a conserved Toll/interleukin-1 resistance domain protein in the Caenorhabditis elegans immune response. Proc Natl Acad Sci USA 2004; 101:6593 - 6598
   PubMed Web of Science ®Google Scholar
• Mallo GV, Kurz CL, Couillault C, Pujol N, Granjeaud S, Kohara Y, et al. Inducible antibacterial defense system in C. elegans. Curr Biol 2002; 12:1209 - 1214
   PubMed Web of Science ®Google Scholar
• O'Rourke D, Baban D, Demidova M, Mott R, Hodgkin J. Genomic clusters, putative pathogen recognition molecules and antimicrobial genes are induced by infection of C. elegans with M. nematophilum. Genome Res 2006; 16:1005 - 1016
   PubMed Web of Science ®Google Scholar
• Shapira M, Hamlin BJ, Rong J, Chen K, Ronen M, Tan MW. A conserved role for a GATA transcription factor in regulating epithelial innate immune responses. Proc Natl Acad Sci USA 2006; 103:14086 - 14091
   PubMed Web of Science ®Google Scholar
• Troemel ER, Chu SW, Reinke V, Lee SS, Ausubel FM, Kim DH. p38 MAPK regulates expression of immune response genes and contributes to longevity in C. elegans. PLoS Genet 2006; 2:183
   PubMed Web of Science ®Google Scholar
• Darby C. Interactions with microbial pathogens. Wormbook 2005; http://www.wormbook.org
   Google Scholar
• Kim DH, Feinbaum R, Alloing G, Emerson FE, Garsin DA, Inoue H, et al. A conserved p38 MAP kinase pathway in Caenorhabditis elegans innate immunity. Science 2002; 297:623 - 626
   PubMed Web of Science ®Google Scholar
• Zugasti O, Ewbank JJ. Neuroimmune regulation of antimicrobial peptide expression by a noncanonical TGFbeta signaling pathway in Caenorhabditis elegans epidermis. Nat Immunol 2009; 10:249 - 256
   PubMed Web of Science ®Google Scholar
• Ewbank JJ. Signaling in the immune response. Wormbook 2006; http://www.wormbook.org
   Google Scholar
• Irazoqui J, Ausubel F. 99th Dahlem Conference on infection, inflammation and chronic inflammatory disorders: Caenorhabditis elegans as a model to study tissues involved in host immunity and microbial pathogenesis. Clinical and Experimental Immunology 2010; 160:48 - 57
   PubMed Web of Science ®Google Scholar
• Bolz DD, Tenor JL, Aballay A. A conserved PMK-1/p38 MAPK is required in C. elegans tissue-specific immune response to Y. pestis infection. J Biol Chem 2010; 285:10832 - 10840
   PubMed Web of Science ®Google Scholar
• Pujol N, Link EM, Liu LX, Kurz CL, Alloing G, Tan MW, et al. A reverse genetic analysis of components of the Toll signaling pathway in Caenorhabditis elegans. Curr Biol 2001; 11:809 - 821
   PubMedGoogle Scholar
• Kawli T, Tan MW. Neuroendocrine signals modulate the innate immunity of Caenorhabditis elegans through insulin signaling. Nat Immunol 2008; 9:1415 - 1424
   Google Scholar
• Evans EA, Kawli T, Tan MW. Pseudomonas aeruginosa suppresses host immunity by activating the DAF-2 insulin-like signaling pathway in Caenorhabditis elegans. PLoS Pathog 2008; 4:1000175
   PubMed Web of Science ®Google Scholar
• Amrit FR, Boehnisch CM, May RC. Phenotypic covariance of longevity, immunity and stress resistance in the Caenorhabditis nematodes. PLoS One 5:9978
   Web of Science ®Google Scholar
• van den Berg MC, Woerlee JZ, Ma H, May RC. Sex-dependent resistance to the pathogenic fungus Cryptococcus neoformans. Genetics 2006; 173:677 - 683
   PubMed Web of Science ®Google Scholar
• Tatar M, Kopelman A, Epstein D, Tu MP, Yin CM, Garofalo RS. A mutant Drosophila insulin receptor homolog that extends life-span and impairs neuroendocrine function. Science 2001; 292:107 - 110
   PubMed Web of Science ®Google Scholar
• Clancy DJ, Gems D, Harshman LG, Oldham S, Stocker H, Hafen E, et al. Extension of life-span by loss of CHICO, a Drosophila insulin receptor substrate protein. Science 2001; 292:104 - 106
   PubMed Web of Science ®Google Scholar
• Libert S, Chao Y, Zwiener J, Pletcher SD. Realized immune response is enhanced in long-lived puc and chico mutants but is unaffected by dietary restriction. Mol Immunol 2008; 45:810 - 817
   PubMed Web of Science ®Google Scholar
• Bluher M, Kahn BB, Kahn CR. Extended longevity in mice lacking the insulin receptor in adipose tissue. Science 2003; 299:572 - 574
   PubMed Web of Science ®Google Scholar
• Holzenberger M, Dupont J, Ducos B, Leneuve P, Geloen A, Even PC, et al. IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice. Nature 2003; 421:182 - 187
   PubMed Web of Science ®Google Scholar
• Kappeler L, De Magalhaes Filho C, Dupont J, Leneuve P, Cervera P, Perin L, et al. Brain IGF-1 receptors control mammalian growth and lifespan through a neuroendocrine mechanism. PLoS Biol 2008; 6:254
   Web of Science ®Google Scholar
• Selman C, Lingard S, Choudhury AI, Batterham RL, Claret M, Clements M, et al. Evidence for lifespan extension and delayed age-related biomarkers in insulin receptor substrate 1 null mice. FASEB J 2008; 22:807 - 818
   PubMed Web of Science ®Google Scholar
• Baba T, Shimizu T, Suzuki Y, Ogawara M, Isono K, Koseki H, et al. Estrogen, insulin and dietary signals cooperatively regulate longevity signals to enhance resistance to oxidative stress in mice. J Biol Chem 2005; 280:16417 - 16426
   PubMed Web of Science ®Google Scholar
• Bonafe M, Barbieri M, Marchegiani F, Olivieri F, Ragno E, Giampieri C, et al. Polymorphic variants of insulin-like growth factor I (IGF-I) receptor and phosphoinositide 3-kinase genes affect IGF-I plasma levels and human longevity: cues for an evolutionarily conserved mechanism of life span control. Journal of Clinical Endocrinology and Metabolism 2003; 88:3299 - 3304
   PubMed Web of Science ®Google Scholar
• Franceschi C, Olivieri F, Marchegiani F, Cardelli M, Cavallone L, Capri M, et al. Genes involved in immune response/inflammation, IGF1/insulin pathway and response to oxidative stress play a major role in the genetics of human longevity: the lesson of centenarians. Mech Ageing Dev 2005; 126:351 - 361
   PubMed Web of Science ®Google Scholar
• Kojima T, Kamei H, Aizu T, Arai Y, Takayama M, Nakazawa S, et al. Association analysis between longevity in the Japanese population and polymorphic variants of genes involved in insulin and insulin-like growth factor 1 signaling pathways. Experimental Gerontology 2004; 39:1595 - 1598
   PubMed Web of Science ®Google Scholar
• Suh Y, Atzmon G, Cho MO, Hwang D, Liu B, Leahy DJ, et al. Functionally significant insulin-like growth factor I receptor mutations in centenarians. Proceedings of the National Academy of Sciences of the United States of America 2008; 105:3438 - 3442
   PubMed Web of Science ®Google Scholar
• van Heemst D, Beekman M, Mooijaart SP, Heijmans BT, Brandt BW, Zwaan BJ, et al. Reduced insulin/IGF-1 signalling and human longevity. Aging Cell 2005; 4:79 - 85
   PubMed Web of Science ®Google Scholar
• 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; 105:13987 - 13992
   PubMed Web of Science ®Google Scholar
• 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 - 6373
   PubMed Web of Science ®Google Scholar
• Cargill SLCJ, Müller HG, Anderson G. Age of ovary determines remaining life expectancy in old ovariectomized mice. Aging Cell 2003; 2:185 - 190
   PubMed Web of Science ®Google Scholar
• Perez GIJA, Wise L, Lipina T, Kanisek M, Bechard A, Takai Y, et al. Absence of the proapoptotic Bax protein extends fertility and alleviates age-related health complications in female mice. Proc Natl Acad Sci USA 2007; 104:5229 - 5234
   PubMed Web of Science ®Google Scholar
• Parker WH, Broder MS, Chang E, Feskanich D, Farquhar C, Liu Z, et al. Ovarian conservation at the time of hysterectomy and long-term health outcomes in the nurses' health study. Obstet Gynecol 2009; 113:1027 - 1037
   PubMed Web of Science ®Google Scholar
• Parker WH, Broder MS, Liu Z, Shoupe D, Farquhar C, Berek JS. Ovarian conservation at the time of hysterectomy for benign disease. Clin Obstet Gynecol 2007; 50:354 - 361
   PubMed Web of Science ®Google Scholar
• Rivera CM, Grossardt BR, Rhodes DJ, Brown RD Jr, Roger VL, Melton LJ 3rd, et al. Increased cardiovascular mortality after early bilateral oophorectomy. Menopause 2009; 16:15 - 23
   PubMed Web of Science ®Google Scholar
• Becker T, Loch G, Beyer M, Zinke I, Aschenbrenner AC, Carrera P, et al. FOXO-dependent regulation of innate immune homeostasis. Nature 463:369 - 373
   PubMed Web of Science ®Google Scholar
• Coffer PJ, Burgering BM. Forkhead-box transcription factors and their role in the immune system. Nat Rev Immunol 2004; 4:889 - 899
   PubMed Web of Science ®Google Scholar
• Jonsson H, Peng SL. Forkhead transcription factors in immunology. Cell Mol Life Sci 2005; 62:397 - 409
   PubMed Web of Science ®Google Scholar
• Salminen A, Huuskonen J, Ojala J, Kauppinen A, Kaarniranta K, Suuronen T. Activation of innate immunity system during aging: NFκB signaling is the molecular culprit of inflamm-aging. Ageing Res Rev 2008; 7:83 - 105
   PubMed Web of Science ®Google Scholar
• Spencer NF, Poynter ME, Im SY, Daynes RA. Constitutive activation of NFkappaB in an animal model of aging. Int Immunol 1997; 9:1581 - 1588
   PubMed Web of Science ®Google Scholar
• Lin L, Hron JD, Peng SL. Regulation of NFkappaB, Th activation and autoinflammation by the forkhead transcription factor Foxo3a. Immunity 2004; 21:203 - 213
   PubMed Web of Science ®Google Scholar
• Peng SL. Immune regulation by Foxo transcription factors. Autoimmunity 2007; 40:462 - 469
   PubMed Web of Science ®Google Scholar
• Salminen A, Ojala J, Huuskonen J, Kauppinen A, Suuronen T, Kaarniranta K. Interaction of aging-associated signaling cascades: inhibition of NFkappaB signaling by longevity factors FoxOs and SIRT1. Cell Mol Life Sci 2008; 65:1049 - 1058
   PubMed Web of Science ®Google Scholar
• Beckman KB, Ames BN. The free radical theory of aging matures. Physiol Rev 1998; 78:547 - 581
   PubMed Web of Science ®Google Scholar
• Harman D. Aging: a theory based on free radical and radiation chemistry. J Gerontol 1956; 11:298 - 300
   PubMedGoogle Scholar
• Fujii M, Matsumoto Y, Tanaka N, Miki K, Suzuki T, Ishii N, et al. Mutations in chemosensory cilia cause resistance to paraquat in nematode Caenorhabditis elegans. J Biol Chem 2004; 279:20277 - 20282
   PubMed Web of Science ®Google Scholar
• Yamawaki TM, Arantes-Oliveira N, Berman JR, Zhang P, Kenyon C. Distinct Activities of the Germline and Somatic Reproductive Tissues in the Regulation of Caenorhabditis elegans Longevity. Genetics 2008; 178:513 - 526
   PubMed Web of Science ®Google Scholar
• Libina NBJ, Kenyon C. Tissue-specific activities of C. elegans DAF-16 in the regulation of lifespan. Cell 2003; 115:489 - 502
   PubMed Web of Science ®Google Scholar
• Doonan R, McElwee JJ, Matthijssens F, Walker GA, Houthoofd K, Back P, et al. Against the oxidative damage theory of aging: superoxide dismutases protect against oxidative stress but have little or no effect on life span in Caenorhabditis elegans. Genes Dev 2008; 22:3236 - 3241
   PubMed Web of Science ®Google Scholar
• Perez VI, Bokov A, Van Remmen H, Mele J, Ran Q, Ikeno Y, et al. Is the oxidative stress theory of aging dead?. Biochim Biophys Acta 2009; 1790:1005 - 1014
   PubMed Web of Science ®Google Scholar
• Van Raamsdonk JM, Hekimi S. Deletion of the mitochondrial superoxide dismutase sod-2 extends lifespan in Caenorhabditis elegans. PLoS Genet 2009; 5:1000361
   PubMed Web of Science ®Google Scholar