Caenorhabditis elegans: What We Can and Cannot Learn from Aging Worms

Antioxidants and Redox Signaling

Volumn 23, Issue 3, 2015, Pages 256-279

  Gruber, Jan ^a,b   Chen, Ce Belle ^a   Fong, Sheng ^c   Ng, Li Fang ^a   Teo, Emelyne ^a   Halliwell, Barry ^a  

^a NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

^b YALE NUS COLLEGE   (Singapore)

^c DUKE NUS MEDICAL SCHOOL   (Singapore)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIOXIDANT; BIOLOGICAL MARKER; FREE RADICAL; MITOCHONDRIAL DNA;

AGING; CAENORHABDITIS ELEGANS; DNA MUTATIONAL ANALYSIS; HORMESIS; HUMAN; IMMUNE SYSTEM; LIFESPAN; MAMMAL; NONHUMAN; OXIDATIVE STRESS; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; ANIMAL; ANIMAL MODEL; GENETICS; IMMUNOLOGY; METABOLISM; MUTATION; OXIDATION REDUCTION REACTION;

AGING; ANIMALS; CAENORHABDITIS ELEGANS; DNA, MITOCHONDRIAL; FREE RADICALS; HUMANS; MAMMALS; MODELS, ANIMAL; MUTATION; OXIDATION-REDUCTION; SIGNAL TRANSDUCTION;

EID: 84974718006     PISSN: 15230864     EISSN: 15577716     Source Type: Journal    
DOI: 10.1089/ars.2014.6210     Document Type: Review

References (276)

1. 2014. Wormbase, Database of C. elegans research groups. www.wormbase.org/resources/laboratory#2-1-5. Accessed November 2014.
2. Aballay A, Drenkard E, Hilbun LR, Ausubel FM. Caenorhabditis elegans innate immune response triggered by Salmonella enterica requires intact LPS and is mediated by a MAPK signaling pathway. Curr Biol 13: 47-52, 2003.
3. Alegado RA and Tan MW. Resistance to antimicrobial peptides contributes to persistence of Salmonella typhimurium in the C. elegans intestine. Cell Microbiol 10: 1259-1273, 2008.
4. Altun ZF and Hall DH. Muscle system, somatic muscle. WormAtlas 2009. DOI: 10.3908/wormatlas.1.7
5. Altun ZF and Hall DH. Nervous system, general description. WormAtlas 2011. DOI: 10.3908/wormatlas.1.18
6. Ardiel EL and Rankin CH. An elegant mind: learning and memory in Caenorhabditis elegans. LearnMem 17: 191-201, 2010.
7. Back P, Braeckman BP, Matthijssens F. ROS in aging Caenorhabditis elegans: damage or signaling? Oxid Med Cell Longev 2012: 608478, 2012.
8. Baeriswyl S, Diard M, Mosser T, Leroy M, Maniere X, Taddei F, Matic I. Modulation of aging profiles in isogenic populations of Caenorhabditis elegans by bacteria causing different extrinsic mortality rates. Biogerontology 11: 53-65, 2010.
9. Banyai L and Patthy L. Amoebapore homologs of Caenorhabditis elegans. Biochim Biophys Acta 1429: 259-264, 1998.
10. Barja G. Updating the mitochondrial free radical theory of aging: an integrated view, key aspects, confounding concepts. Antioxid Redox Signal 19: 1420-1445, 2013.
11. Baur JA, Chen D, Chini EN, Chua K, Cohen HY, de Cabo R, Deng C, Dimmeler S, Gius D, Guarente LP, Helfand SL, Imai S, Itoh H, Kadowaki T, Koya D, Leeuwenburgh C, McBurney M, Nabeshima Y, Neri C, Oberdoerffer P, Pestell RG, Rogina B, Sadoshima J, Sartorelli V, Serrano M, Sinclair DA, Steegborn C, Tatar M, Tissenbaum HA, Tong Q, Tsubota K, Vaquero A, Verdin E. Dietary restriction: standing up for sirtuins. Science 329: 1012-1013; author reply 1013-1014, 2010.
12. Bello S, Krogsboll LT, Gruber J, Zhao ZJ, Fischer D, Hrobjartsson A. Lack of blinding of outcome assessors in animal model experiments implies risk of observer bias. J Clin Epidemiol 67: 973-983, 2014.
13. Benton MJ and Ayala FJ. Dating the tree of life. Science 300: 1698-1700, 2003.
14. Bernet JD, Doles JD, Hall JK, Kelly Tanaka K, Carter TA, Olwin BB. p38 MAPK signaling underlies a cellautonomous loss of stem cell self-renewal in skeletal muscle of aged mice. Nat Med 20: 265-271, 2014.
15. Bjelakovic G, Nikolova D, Gluud C. Meta-regression analyses, meta-analyses, trial sequential analyses of the effects of supplementation with beta-carotene, vitamin A, vitamin E singly or in different combinations on all-cause mortality: do we have evidence for lack of harm? PLoS One 8: e74558, 2013.
16. Bjelakovic G, Nikolova D, Gluud C. Antioxidant supplements and mortality. Curr Opin Clin Nutr Metab Care 17: 40-44, 2014.
17. Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane Database Syst Rev 3: CD007176, 2012.
18. Borgwardt S, Hammann F, Scheffler K, Kreuter M, Drewe J, Beglinger C. Neural effects of green tea extract on dorsolateral prefrontal cortex. Eur J Clin Nutr 66: 1187-1192, 2012.
19. Brand MD. The role of mitochondria in longevity and healthspan. Longev Healthspan 3: 7, 2014.
20. Braungart E, Gerlach M, Riederer P, Baumeister R, Hoener MC. Caenorhabditis elegans MPP+ model of Parkinson's disease for high-throughput drug screenings. Neurodegener Dis 1: 175-183, 2004.
21. Brown MK, Evans JL, Luo Y. Beneficial effects of natural antioxidants EGCG and alpha-lipoic acid on life span and age-dependent behavioral declines in Caenorhabditis elegans. Pharmacol Biochem Behav 85: 620-628, 2006.
22. Bruunsgaard H,ersen-Ranberg K, Hjelmborg J, Pedersen BK, Jeune B. Elevated levels of tumor necrosis factor alpha and mortality in centenarians. Am J Med 115: 278-283, 2003.
23. Bua E, Johnson J, Herbst A, Delong B, McKenzie D, Salamat S, Aiken JM. Mitochondrial DNA-deletion mutations accumulate intracellularly to detrimental levels in aged human skeletal muscle fibers. Am J Hum Genet 79: 469-480, 2006.
24. Budovskaya YV, Wu K, Southworth LK, Jiang M, Tedesco P, Johnson TE, Kim SK. An elt-3/elt-5/elt-6 GATA transcription circuit guides aging in C. elegans. Cell 134: 291-303, 2008.
25. Butterfield DA, Swomley AM, Sultana R. Amyloid beta-peptide (1-42)-induced oxidative stress in Alzheimer disease: importance in disease pathogenesis and progression. Antioxid Redox Signal 19: 823-835, 2013.
26. Cabreiro F, Ackerman D, Doonan R, Araiz C, Back P, Papp D, Braeckman BP, Gems D. Increased life span from overexpression of superoxide dismutase in Caenorhabditis elegans is not caused by decreased oxidative damage. Free Radic Biol Med 51: 1575-1582, 2011.
27. Cabrejo L, Guyant-Marechal L, Laquerriere A, Vercelletto M, De la Fourniere F, Thomas-Anterion C, Verny C, Letournel F, Pasquier F, Vital A, Checler F, Frebourg T, Campion D, Hannequin D. Phenotype associated with APP duplication in five families. Brain 129: 2966-2976, 2006.
28. Cacho-Valadez B, Munoz-Lobato F, Pedrajas JR, Cabello J, Fierro-Gonzalez JC, Navas P, Swoboda P, Link CD, Miranda-Vizuete A. The characterization of the Caenorhabditis elegans mitochondrial thioredoxin system uncovers an unexpected protective role of thioredoxin reductase 2 in beta-amyloid peptide toxicity. Antioxid Redox Signal 16: 1384-1400, 2012.
29. Calabrese EJ and Baldwin LA. The hormetic doseresponse model is more common than the threshold model in toxicology. Toxicol Sci 71: 246-250, 2003.
30. Cavalier-Smith T. Origin of mitochondria by intracellular enslavement of a photosynthetic purple bacterium. Proc Biol Sci 273: 1943-1952, 2006.
31. Chavez V, Mohri-Shiomi A, Garsin DA. Ce-Duox1/BLI-3 generates reactive oxygen species as a protective innate immune mechanism in Caenorhabditis elegans. Infect Immun 77: 4983-4989, 2009.
32. Chege PM and McColl G. Caenorhabditis elegans: a model to investigate oxidative stress and metal dyshomeostasis in Parkinson's disease. Front Aging Neurosci 6: 89, 2014.
33. Christen WG, Glynn RJ, Chew EY, Buring JE. Vitamin E and age-related macular degeneration in a randomized trial of women. Ophthalmology 117: 1163-1168, 2010.
34. Chuang CF and Bargmann CI. A Toll-interleukin 1 repeat protein at the synapse specifies asymmetric odorant receptor expression via ASK1 MAPKKK signaling. Genes Dev 19: 270-281, 2005.
35. Colman RJ, Beasley TM, Kemnitz JW, Johnson SC, Weindruch R,erson RM. Caloric restriction reduces age-related and all-cause mortality in rhesus monkeys. Nat Commun 5: 3557, 2014.
36. Couillault C, Pujol N, Reboul J, Sabatier L, Guichou JF, Kohara Y, Ewbank JJ. TLR-independent control of innate immunity in Caenorhabditis elegans by the TIR domain adaptor protein TIR-1, an ortholog of human SARM. Nat Immunol 5: 488-494, 2004.
37. Cypser JR and Johnson TE. Multiple stressors in Caenorhabditis elegans induce stress hormesis and extended longevity. J Gerontol A Biol Sci Med Sci 57: B109-B114, 2002.
38. Dai DF, Chiao YA, Marcinek DJ, Szeto HH, Rabinovitch PS. Mitochondrial oxidative stress in aging and healthspan. Longev Healthspan 3: 6, 2014.
39. Daigle I and Li C. Apl-1, a Caenorhabditis elegans gene encoding a protein related to the human beta-amyloid protein precursor. Proc Natl Acad Sci USA 90: 12045-12049, 1993.
40. David DC, Ollikainen N, Trinidad JC, Cary MP, Burlingame AL, Kenyon C. Widespread protein aggregation as an inherent part of aging in C. elegans. PLoS Biol 8: e1000450, 2010.
41. De Haes W, Frooninckx L, Van Assche R, Smolders A, Depuydt G, Billen J, Braeckman BP, Schoofs L, Temmerman L. Metformin promotes lifespan through mitohormesis via the peroxiredoxin PRDX-2. Proc Natl Acad Sci USA 111: E2501-E2509, 2014.
42. De Simoni S, Goemaere J, Knoops B. Silencing of peroxiredoxin 3 and peroxiredoxin 5 reveals the role of mitochondrial peroxiredoxins in the protection of human neuroblastoma SH-SY5Y cells toward MPP+ . Neurosci Lett 433: 219-224, 2008.
43. Diaz F, Bayona-Bafaluy MP, Rana M, Mora M, Hao H, Moraes CT. Human mitochondrial DNA with large deletions repopulates organelles faster than full-length genomes under relaxed copy number control. Nucleic Acids Res 30: 4626-4633, 2002.
44. Doonan R, McElwee JJ, Matthijssens F, Walker GA, Houthoofd K, Back P, Matscheski A, Vanfleteren JR, Gems D. 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 22: 3236-3241, 2008.
45. Dosanjh LE, Brown MK, Rao G, Link CD, Luo Y. Behavioral phenotyping of a transgenic Caenorhabditis elegans expressing neuronal amyloid-beta. J Alzheimers Dis 19: 681-690, 2010.
46. Doss M. Shifting the paradigm in radiation safety. Dose Response 10: 562-583, 2012.
47. Drachman DA. Do we have brain to spare? Neurology 64: 2004-2005, 2005.
48. Draeger CL, Naves A, Marques N, Baptistella AB, Carnauba RA, Paschoal V, Nicastro H. Controversies of antioxidant vitamins supplementation in exercise: ergogenic or ergolytic effects in humans? J Int Soc Sports Nutr 11: 4, 2014.
49. Drake J, Link CD, Butterfield DA. Oxidative stress precedes fibrillar deposition of Alzheimer's disease amyloid beta-peptide (1-42) in a transgenic Caenorhabditis elegans model. Neurobiol Aging 24: 415-420, 2003.
50. Duan Z and Sesti F. A Caenorhabditis elegans model system for amylopathy study. J Vis Exp: e50435, 2013.
51. Dunn KB, Heffler M, Golubovskaya VM. Evolving therapies and FAK inhibitors for the treatment of cancer. Anticancer Agents Med Chem 10: 722-734, 2010.
52. Edens WA, Sharling L, Cheng G, Shapira R, Kinkade JM, Lee T, Edens HA, Tang X, Sullards C, Flaherty DB, Benian GM, Lambeth JD. Tyrosine cross-linking of extracellular matrix is catalyzed by Duox, a multidomain oxidase/peroxidase with homology to the phagocyte oxidase subunit gp91phox. J Cell Biol 154: 879-891, 2001.
53. Elchuri S, Oberley TD, Qi W, Eisenstein RS, Jackson Roberts L, Van Remmen H, Epstein CJ, Huang TT. CuZnSOD deficiency leads to persistent and widespread oxidative damage and hepatocarcinogenesis later in life. Oncogene 24: 367-380, 2005.
54. Ewald CY, Cheng R, Tolen L, Shah V, Gillani A, Nasrin A, Li C. Pan-neuronal expression of APL-1, an APPrelated protein, disrupts olfactory, gustatory, touch plasticity in Caenorhabditis elegans. J Neurosci 32: 10156-10169, 2012.
55. Finch CE, Pike MC, Witten M. Slow mortality rate accelerations during aging in some animals approximate that of humans. Science 249: 902-905, 1990.
56. Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391: 806-811, 1998.
57. Fornalski KW and Dobrzynski L. The healthy worker effect and nuclear industry workers. Dose Response 8: 125-147, 2010.
58. Fukai T and Ushio-Fukai M. Superoxide dismutases: role in redox signaling, vascular function, diseases. Antioxid Redox Signal 15: 1583-1606, 2011.
59. Fukui H and Moraes CT. Mechanisms of formation and accumulation of mitochondrial DNA deletions in aging neurons. Hum Mol Genet 18: 1028-1036, 2009.
60. Garigan D, Hsu AL, Fraser AG, Kamath RS, Ahringer J, Kenyon C. Genetic analysis of tissue aging in Caenorhabditis elegans: a role for heat-shock factor and bacterial proliferation. Genetics 161: 1101-1112, 2002.
61. Garsin DA, Villanueva JM, Begun J, Kim DH, Sifri CD, Calderwood SB, Ruvkun G, Ausubel FM. Long-lived C. elegans daf-2 mutants are resistant to bacterial pathogens. Science 300: 1921, 2003.
62. Gems D and de la Guardia Y. Alternative Perspectives on Aging in Caenorhabditis elegans: Reactive Oxygen Species or Hyperfunction? Antioxid Redox Signal 19: 321-329, 2013.
63. Gems D and Doonan R. Antioxidant defense and aging in C. elegans: is the oxidative damage theory of aging wrong? Cell Cycle 8: 1681-1687, 2009.
64. Gems D and Partridge L. Genetics of longevity in model organisms: debates and paradigm shifts. Annu Rev Physiol 75: 621-644, 2013.
65. Giglio MP, Hunter T, Bannister JV, Bannister WH, Hunter GJ. The manganese superoxide dismutase gene of Caenorhabditis elegans. Biochem Mol Biol Int 33: 37-40, 1994.
66. Glenner GG and Wong CW. Alzheimer's disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun 120: 885-890, 1984.
67. Gomez-Cabrera MC, Domenech E, Romagnoli M, Arduini A, Borras C, Pallardo FV, Sastre J, Vina J. Oral administration of vitamin C decreases muscle mitochondrial biogenesis and hampers training-induced adaptations in endurance performance. Am J Clin Nutr 87: 142-149, 2008.
68. Goth L and Eaton JW. Hereditary catalase deficiencies and increased risk of diabetes. Lancet 356: 1820-1821, 2000.
69. Goyal MM and Basak A. Human catalase: looking for complete identity. Protein Cell 1: 888-897, 2010.
70. Gralle M and Ferreira ST. Structure and functions of the human amyloid precursor protein: the whole is more than the sum of its parts. Prog Neurobiol 82: 11-32, 2007.
71. Gruber J, Ng LF, Fong S, Wong YT, Koh SA, Chen CB, Shui G, Cheong WF, Schaffer S, Wenk MR, Halliwell B. Mitochondrial changes in aging Caenorhabditis elegans-what do we learn from superoxide dismutase knockouts? PLoS One 6: e19444, 2011.
72. Gruber J, Ng LF, Poovathingal SK, Halliwell B. Deceptively simple but simply deceptive-Caenorhabditis elegans lifespan studies: considerations for aging and antioxidant effects. FEBS Lett 583: 3377-3387, 2009.
73. Gruber J, Schaffer S, Halliwell B. The mitochondrial free radical theory of aging-where do we stand? Front Biosci 13: 6554-6579, 2008.
74. Grundke-Iqbal I, Iqbal K, Tung YC, Quinlan M, Wisniewski HM, Binder LI. Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology. Proc Natl Acad Sci USA 83: 4913-4917, 1986.
75. Ha CW and Huh WK. The implication of Sir2 in replicative aging and senescence in Saccharomyces cerevisiae. Aging (Albany NY) 3: 319-324, 2011.
76. Hall DH and Russell RL. The posterior nervous system of the nematode Caenorhabditis elegans: serial reconstruction of identified neurons and complete pattern of synaptic interactions. J Neurosci 11: 1-22, 1991.
77. Halliwell B. Are polyphenols antioxidants or prooxidants? What do we learn from cell culture and in vivo studies? Arch Biochem Biophys 476: 107-112, 2008.
78. Halliwell B. The antioxidant paradox: less paradoxical now? Br J Clin Pharmacol 75: 637-644, 2013.
79. Halliwell B. Cell culture, oxidative stress, antioxidants: avoiding pitfalls. Biomed J 37: 99-105, 2014.
80. Halliwell B and Gutteridge J. Free Radicals in Biology and Medicine, edition five.Oxford: Oxford University Press, 2015.
81. Harman D. Aging: a theory based on free radical and radiation chemistry. J Gerontol 11: 298-300, 1956.
82. Harman D. The biologic clock: the mitochondria? J Am Geriatr Soc 20: 145-147, 1972.
83. Harris TB, Ferrucci L, Tracy RP, Corti MC, Wacholder S, Ettinger WH, Jr., Heimovitz H, Cohen HJ, Wallace R. Associations of elevated interleukin-6 and C-reactive protein levels with mortality in the elderly. Am J Med 106: 506-512, 1999.
84. Hartwig K, Heidler T, Moch J, Daniel H, Wenzel U. Feeding a ROS-generator to Caenorhabditis elegans leads to increased expression of small heat shock protein HSP-16.2 and hormesis. Genes Nutr 4: 59-67, 2009.
85. Hayflick L. The future of aging. Nature 408: 267-269, 2000.
86. Hedges SB, Blair JE, Venturi ML, Shoe JL. A molecular timescale of eukaryote evolution and the rise of complex multicellular life. BMC Evol Biol 4: 2, 2004.
87. Herndon LA, Schmeissner PJ, Dudaronek JM, Brown PA, Listner KM, Sakano Y, Paupard MC, Hall DH, Driscoll M. Stochastic and genetic factors influence tissue-specific decline in aging C. elegans. Nature 419: 808-814, 2002.
88. Hinerfeld D, Traini MD, Weinberger RP, Cochran B, Doctrow SR, Harry J, Melov S. Endogenous mitochondrial oxidative stress: neurodegeneration, proteomic analysis, specific respiratory chain defects, efficacious antioxidant therapy in superoxide dismutase 2 null mice. J Neurochem 88: 657-667, 2004.
89. Ho YS, Xiong Y, Ma W, Spector A, Ho DS. Mice lacking catalase develop normally but show differential sensitivity to oxidant tissue injury. J Biol Chem 279: 32804-32812, 2004.
90. Hoeven R, McCallum KC, Cruz MR, Garsin DA. Ce-Duox1/BLI-3 generated reactive oxygen species trigger protective SKN-1 activity via p38 MAPK signaling during infection in C. elegans. PLoS Pathog 7: e1002453, 2011.
91. Honda Y, Tanaka M, Honda S. Modulation of longevity and diapause by redox regulation mechanisms under the insulin-like signaling control in Caenorhabditis elegans. Exp Gerontol 43: 520-529, 2008.
92. Houthoofd K, Johnson TE, Vanfleteren JR. Dietary restriction in the nematode Caenorhabditis elegans. J Gerontol A Biol Sci Med Sci 60: 1125-1131, 2005.
93. Huang TT, Carlson EJ, Kozy HM, Mantha S, Goodman SI, Ursell PC, Epstein CJ. Genetic modification of prenatal lethality and dilated cardiomyopathy in Mn superoxide dismutase mutant mice. Free Radic Biol Med 31: 1101-1110, 2001.
94. Hunt PR, Son TG, Wilson MA, Yu QS, Wood WH, Zhang Y, Becker KG, Greig NH, Mattson MP, Camandola S, Wolkow CA. Extension of lifespan in C. elegans by naphthoquinones that act through stress hormesis mechanisms. PLoS One 6: e21922, 2011.
95. Hunter T, Bannister WH, Hunter GJ. Cloning, expression, characterization of two manganese superoxide dismutases from Caenorhabditis elegans. J Biol Chem 272: 28652-28659, 1997.
96. Hussain SP, Hofseth LJ, Harris CC. Radical causes of cancer. Nat Rev Cancer 3: 276-285, 2003.
97. Imai S, Armstrong CM, Kaeberlein M, Guarente L. Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature 403: 795-800, 2000.
98. Irazoqui JE, Urbach JM, Ausubel FM. Evolution of host innate defence: insights from Caenorhabditis elegans and primitive invertebrates. Nat Rev Immunol 10: 47-58, 2010.
99. Isermann K, Liebau E, Roeder T, Bruchhaus I. A peroxiredoxin specifically expressed in two types of pharyngeal neurons is required for normal growth and egg production in Caenorhabditis elegans. J Mol Biol 338: 745-755, 2004.
100. Jain C, Pastor K, Gonzalez AY, Lorenz MC, Rao RP. The role of Candida albicans AP-1 protein against host derived ROS in in vivo models of infection. Virulence 4: 67-76, 2013.
101. Jakobsen H, Bojer MS, Marinus MG, Xu T, Struve C, Krogfelt KA, Lobner-Olesen A. The alkaloid compound harmane increases the lifespan of Caenorhabditis elegans during bacterial infection, by modulating the nematode's innate immune response. PLoS One 8: e60519, 2013.
102. Jang YC, Perez VI, Song W, Lustgarten MS, Salmon AB, Mele J, Qi W, Liu Y, Liang H, Chaudhuri A, Ikeno Y, Epstein CJ, Van Remmen H, Richardson A. Overexpression of Mn superoxide dismutase does not increase life span in mice. J Gerontol A Biol Sci Med Sci 64: 1114-1125, 2009.
103. Jee C, Vanoaica L, Lee J, Park BJ, Ahnn J. Thioredoxin is related to life span regulation and oxidative stress response in Caenorhabditis elegans. Genes Cells 10: 1203-1210, 2005.
104. Johnson TE. Increased life-span of age-1 mutants in Caenorhabditis elegans and lower Gompertz rate of aging. Science 249: 908-912, 1990.
105. Johnson TE. 25 years after age-1: genes, interventions and the revolution in aging research. Exp Gerontol 48: 640-643, 2013.
106. Johnson TE and Hartman PS. Radiation effects on life span in Caenorhabditis elegans. J Gerontol 43: B137-B141, 1988.
107. Johnson TE, Wu D, Tedesco P, Dames S, Vaupel JW. Age-specific demographic profiles of longevity mutants in Caenorhabditis elegans show segmental effects. J Gerontol A Biol Sci Med Sci 56: B331-B139, 2001.
108. Kahn A and Olsen A. Stress to the rescue: is hormesis a 'cure' for aging? Dose Response 8: 48-52, 2009.
109. Kamath RS, Fraser AG, Dong Y, Poulin G, Durbin R, Gotta M, Kanapin A, Le Bot N, Moreno S, Sohrmann M, Welchman DP, Zipperlen P, Ahringer J. Systematic functional analysis of the Caenorhabditis elegans genome using RNAi. Nature 421: 231-237, 2003.
110. Keaney M and Gems D. No increase in lifespan in Caenorhabditis elegans upon treatment with the superoxide dismutase mimetic EUK-8. Free Radic Biol Med 34: 277-282, 2003.
111. Keaney M, Matthijssens F, Sharpe M, Vanfleteren J, Gems D. Superoxide dismutase mimetics elevate superoxide dismutase activity in vivo but do not retard aging in the nematode Caenorhabditis elegans. Free Radic Biol Med 37: 239-250, 2004.
112. Kedziora J and Bartosz G. Down's syndrome: a pathology involving the lack of balance of reactive oxygen species. Free Radic Biol Med 4: 317-330, 1988.
113. Kennedy BK, Austriaco NR, Jr., Zhang J, Guarente L. Mutation in the silencing gene SIR4 can delay aging in S. cerevisiae. Cell 80: 485-496, 1995.
114. Kenyon CJ. The genetics of aging. Nature 464: 504-512, 2010.
115. Kim DH, Feinbaum R, Alloing G, Emerson FE, Garsin DA, Inoue H, Tanaka-Hino M, Hisamoto N, Matsumoto K, Tan MW, Ausubel FM. A conserved p38 MAP kinase pathway in Caenorhabditis elegans innate immunity. Science 297: 623-626, 2002.
116. Kim J, Takahashi M, Shimizu T, Shirasawa T, Kajita M, Kanayama A, Miyamoto Y. Effects of a potent antioxidant, platinum nanoparticle, on the lifespan of Caenorhabditis elegans. Mech Aging Dev 129: 322-331, 2008.
117. Kim JH, Park SH, Moon YW, Hwang S, Kim D, Jo SH, Oh SB, Kim JS, Jahng JW, Lee JH, Lee SJ, Choi SY, Park K. Histamine H1 receptor induces cytosolic calcium increase and aquaporin translocation in human salivary gland cells. J Pharmacol Exp Ther 330: 403-412, 2009.
118. King LS, Kozono D, Agre P. From structure to disease: the evolving tale of aquaporin biology. Nat Rev Mol Cell Biol 5: 687-698, 2004.
119. Kirienko NV, Mani K, Fay DS. Cancer models in Caenorhabditis elegans. Dev Dyn 239: 1413-1448, 2010.
120. Kirkwood TB. Understanding aging from an evolutionary perspective. J Intern Med 263: 117-127, 2008.
121. Kobayashi M, Sugiyama H, Wang DH, Toda N, Maeshima Y, Yamasaki Y, Masuoka N, Yamada M, Kira S, Makino H. Catalase deficiency renders remnant kidneys more susceptible to oxidant tissue injury and renal fibrosis in mice. Kidney Int 68: 1018-1031, 2005.
122. Koh K and Rothman JH. ELT-5 and ELT-6 are required continuously to regulate epidermal seam cell differentiation and cell fusion in C. elegans. Development 128: 2867-2880, 2001.
123. Kokoszka JE, Coskun P, Esposito LA, Wallace DC. Increased mitochondrial oxidative stress in the Sod2 ( +/-) mouse results in the age-related decline of mitochondrial function culminating in increased apoptosis. Proc Natl Acad Sci USA 98: 2278-2283, 2001.
124. Krabbe KS, Pedersen M, Bruunsgaard H. Inflammatory mediators in the elderly. Exp Gerontol 39: 687-699, 2004.
125. Kraemer BC, Zhang B, Leverenz JB, Thomas JH, Trojanowski JQ, Schellenberg GD. Neurodegeneration and defective neurotransmission in a Caenorhabditis elegans model of tauopathy. Proc Natl Acad Sci USA 100: 9980-9985, 2003.
126. Kujoth GC, Bradshaw PC, Haroon S, Prolla TA. The role of mitochondrial DNA mutations in mammalian aging. PLoS Genet 3: e24, 2007.
127. Kumsta C, Thamsen M, Jakob U. Effects of oxidative stress on behavior, physiology, the redox thiol proteome of Caenorhabditis elegans. Antioxid Redox Signal 14: 1023-1037, 2011.
128. Lebovitz RM, Zhang H, Vogel H, Cartwright J, Jr., Dionne L, Lu N, Huang S, Matzuk MM. Neurodegeneration, myocardial injury, perinatal death in mitochondrial superoxide dismutase-deficient mice. Proc Natl Acad Sci USA 93: 9782-9787, 1996.
129. Lee TH, Kim SU, Yu SL, Kim SH, Park DS, Moon HB, Dho SH, Kwon KS, Kwon HJ, Han YH, Jeong S, Kang SW, Shin HS, Lee KK, Rhee SG, Yu DY. Peroxiredoxin II is essential for sustaining life span of erythrocytes in mice. Blood 101: 5033-5038, 2003.
130. Lettre G and Hengartner MO. Developmental apoptosis in C. elegans: a complex scenario. Nat Rev Mol Cell Biol 7: 97-108, 2006.
131. Leung MC, Williams PL, Benedetto A, Au C, Helmcke KJ, Aschner M, Meyer JN. Caenorhabditis elegans: an emerging model in biomedical and environmental toxicology. Toxicol Sci 106: 5-28, 2008.
132. Li J and Le W. Modeling neurodegenerative diseases in Caenorhabditis elegans. Exp Neurol 250: 94-103, 2013.
133. Li L, Shoji W, Takano H, Nishimura N, Aoki Y, Takahashi R, Goto S, Kaifu T, Takai T, Obinata M. Increased susceptibility of MER5 (peroxiredoxin III) knockout mice to LPS-induced oxidative stress. Biochem Biophys Res Commun 355: 715-721, 2007.
134. Li Y, Huang TT, Carlson EJ, Melov S, Ursell PC, Olson JL, Noble LJ, Yoshimura MP, Berger C, Chan PH, Wallace DC, Epstein CJ. Dilated cardiomyopathy and neonatal lethality in mutant mice lacking manganese superoxide dismutase. Nat Genet 11: 376-381, 1995.
135. Libby P. Inflammation in atherosclerosis. Nature 420: 868-874, 2002.
136. 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 101: 6593-6598, 2004.
137. Licastro F, Candore G, Lio D, Porcellini E, Colonna-Romano G, Franceschi C, Caruso C. Innate immunity and inflammation in aging: a key for understanding agerelated diseases. Immun Aging 2: 8, 2005.
138. Lin L, Hron JD, Peng SL. Regulation of NF-kappaB, Th activation, autoinflammation by the forkhead transcription factor Foxo3a. Immunity 21: 203-213, 2004.
139. Link CD. Expression of human beta-amyloid peptide in transgenic Caenorhabditis elegans. Proc Natl Acad Sci USA 92: 9368-9372, 1995.
140. Link CD. C. elegans models of age-associated neurodegenerative diseases: lessons from transgenic worm models of Alzheimer's disease. Exp Gerontol 41: 1007-1013, 2006.
141. Liochev SI. Reflections on the theories of aging, of oxidative stress, of science in general. Is it time to abandon the free radical (oxidative stress) theory of aging? Antioxid Redox Signal 23: 187-207, 2015.
142. Lipsky NG and Pedersen PL. Mitochondrial turnover in animal cells. Half-lives of mitochondria and mitochondrial subfractions of rat liver based on [14C]bicarbonate incorporation. J Biol Chem 256: 8652-8657, 1981.
143. Lithgow GJ, White TM, Hinerfeld DA, Johnson TE. Thermotolerance of a long-lived mutant of Caenorhabditis elegans. J Gerontol 49: B270-B276, 1994.
144. 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 92: 7540-7544, 1995.
145. Liu S, Saul N, Pan B, Menzel R, Steinberg CE. The non-target organism Caenorhabditis elegans withstands the impact of sulfamethoxazole. Chemosphere 93: 2373-2380, 2013.
146. Lockshin RA and Zakeri Z. Cell death in health and disease. J Cell Mol Med 11: 1214-1224, 2007.
147. Mak JCW. Potential role of green tea catechins in various disease therapies: progress and promise. Clin Exp Pharmacol Physiol 39: 265-273, 2012.
148. Mallo GV, Kurz CL, Couillault C, Pujol N, Granjeaud S, Kohara Y, Ewbank JJ. Inducible antibacterial defense system in C. elegans. Curr Biol 12: 1209-1214, 2002.
149. Manevich Y and Fisher AB. Peroxiredoxin 6, a 1-Cys peroxiredoxin, functions in antioxidant defense and lung phospholipid metabolism. Free Radic Biol Med 38: 1422-1432, 2005.
150. Mao P, Manczak M, Calkins MJ, Truong Q, Reddy TP, Reddy AP, Shirendeb U, Lo HH, Rabinovitch PS, Reddy PH. Mitochondria-targeted catalase reduces abnormal APP processing, amyloid beta production and BACE1 in a mouse model of Alzheimer's disease: implications for neuroprotection and lifespan extension. Hum Mol Genet 21: 2973-2990, 2012.
151. Masoro EJ. The role of hormesis in life extension by dietary restriction. Interdiscip Top Gerontol 35: 1-17, 2007.
152. Matsui M, Oshima M, Oshima H, Takaku K, Maruyama T, Yodoi J, Taketo MM. Early embryonic lethality caused by targeted disruption of the mouse thioredoxin gene. Dev Biol 178: 179-185, 1996.
153. Mattson MP. Dietary factors, hormesis and health. Aging Res Rev 7: 43-48, 2008.
154. McColl BW, Rothwell NJ, Allan SM. Systemic inflammatory stimulus potentiates the acute phase and CXC chemokine responses to experimental stroke and exacerbates brain damage via interleukin-1-and neutrophildependent mechanisms. J Neurosci 27: 4403-4412, 2007.
155. McCord JM. Superoxide dismutase, lipid peroxidation, bell-shaped dose response curves. Dose Response 6: 223-238, 2008.
156. McCord JM and Fridovich I. Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). J Biol Chem 244: 6049-6055, 1969.
157. McElwee J, Bubb K, Thomas JH. Transcriptional outputs of the Caenorhabditis elegans forkhead protein DAF-16. Aging Cell 2: 111-121, 2003.
158. McElwee JJ, Schuster E, Blanc E, Piper MD, Thomas JH, Patel DS, Selman C, Withers DJ, Thornton JM, Partridge L, Gems D. Evolutionary conservation of regulated longevity assurance mechanisms. Genome Biol 8: R132, 2007.
159. McGeer EG and McGeer PL. The importance of inflammatory mechanisms in Alzheimer disease. Exp Gerontol 33: 371-378, 1998.
160. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer'disease: Report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology 34: 939-944, 1984.
161. Melov S, Hertz GZ, Stormo GD, Johnson TE. Detection of deletions in the mitochondrial genome of Caenorhabditis elegans. Nucleic Acids Res 22: 1075-1078, 1994.
162. Melov S, Lithgow GJ, Fischer DR, Tedesco PM, Johnson TE. Increased frequency of deletions in the mitochondrial genome with age of Caenorhabditis elegans. Nucleic Acids Res 23: 1419-1425, 1995.
163. Menzies RA and Gold PH. The turnover of mitochondria in a variety of tissues of young adult and aged rats. J Biol Chem 246: 2425-2429, 1971.
164. Merzenich H, Hammer GP, Troltzsch K, Ruecker K, Buncke J, Fehringer F, Blettner M. Mortality risk in a historical cohort of nuclear power plant workers in Germany: results from a second follow-up. Radiat Environ Biophys 53: 405-416, 2014.
165. Meyer JN, Boyd WA, Azzam GA, Haugen AC, Freedman JH, Van Houten B. Decline of nucleotide excision repair capacity in aging Caenorhabditis elegans. Genome Biol 8: R70, 2007.
166. Mine M, Okumura Y, Ichimaru M, Nakamura T, Kondo S. Apparently beneficial effect of low to intermediate doses of A-bomb radiation on human lifespan. Int J Radiat Biol 58: 1035-1043, 1990.
167. Minois N, Sykacek P, Godsey B, Kreil DP. RNA interference in aging research-a mini-review. Gerontology 56: 496-506, 2010.
168. Miranda-Vizuete A, Fierro Gonzalez JC, Gahmon G, Burghoorn J, Navas P, Swoboda P. Lifespan decrease in a Caenorhabditis elegans mutant lacking TRX-1, a thioredoxin expressed in ASJ sensory neurons. FEBS Lett 580: 484-490, 2006.
169. Miwa S, Lawless C, von Zglinicki T. Mitochondrial turnover in liver is fast in vivo and is accelerated by dietary restriction: application of a simple dynamic model. Aging Cell 7: 920-923, 2008.
170. Mohri-Shiomi A and Garsin DA. Insulin signaling and the heat shock response modulate protein homeostasis in the Caenorhabditis elegans intestine during infection. J Biol Chem 283: 194-201, 2008.
171. Moreno-Arriola E, Cardenas-Rodriguez N, Coballase-Urrutia E, Pedraza-Chaverri J, Carmona-Aparicio L, Ortega-Cuellar D. Caenorhabditis elegans: a useful model for studying metabolic disorders in which oxidative stress is a contributing factor. Oxid Med Cell Longev 2014: 705253, 2014.
172. Morley JE and Farr SA. The role of amyloid-beta in the regulation of memory. Biochem Pharmacol 88: 479-485, 2014.
173. Muller UC and Zheng H. Physiological functions of APP family proteins. Cold Spring Harb Perspect Med 2: a006288, 2012.
174. Murphy CT, McCarroll SA, Bargmann CI, Fraser A, Kamath RS, Ahringer J, Li H, Kenyon C. Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans. Nature 424: 277-283, 2003.
175. Naiman S and Cohen HY. The contentious history of sirtuin debates. Rambam Maimonides Med J 3: e0022, 2012.
176. Nass R and Blakely RD. The Caenorhabditis elegans dopaminergic system: opportunities for insights into dopamine transport and neurodegeneration. Annu Rev Pharmacol Toxicol 43: 521-544, 2003.
177. Nass R, Hall DH, Miller DM, 3rd, Blakely RD. Neurotoxin-induced degeneration of dopamine neurons in Caenorhabditis elegans. Proc Natl Acad Sci USA 99: 3264-3269, 2002.
178. Neumann CA, Krause DS, Carman CV, Das S, Dubey DP, Abraham JL, Bronson RT, Fujiwara Y, Orkin SH, Van Etten RA. Essential role for the peroxiredoxin Prdx1 in erythrocyte antioxidant defence and tumour suppression. Nature 424: 561-565, 2003.
179. Ng LF, Gruber J, Cheah IK, Goo CK, Cheong WF, Shui G, Sit KP, Wenk MR, Halliwell B. The mitochondriatargeted antioxidant MitoQ extends lifespan and improves healthspan of a transgenic Caenorhabditis elegans model of Alzheimer disease. Free Radic Biol Med 71: 390-401, 2014.
180. Nonaka M and Kimura A. Genomic view of the evolution of the complement system. Immunogenetics 58: 701-713, 2006.
181. O'Neill LA, Fitzgerald KA, Bowie AG. The Toll-IL-1 receptor adaptor family grows to five members. Trends Immunol 24: 286-290, 2003.
182. O'Rourke D, Baban D, Demidova M, Mott R, Hodgkin J. Genomic clusters, putative pathogen recognition molecules, antimicrobial genes are induced by infection of C. elegans with M. nematophilum. Genome Res 16: 1005-1016, 2006.
183. Ogata M. Acatalasemia. Hum Genet 86: 331-340, 1991.
184. Olahova M, Taylor SR, Khazaipoul S, Wang J, Morgan BA, Matsumoto K, Blackwell TK, Veal EA. A redoxsensitive peroxiredoxin that is important for longevity has tissue-and stress-specific roles in stress resistance. Proc Natl Acad Sci USA 105: 19839-19844, 2008.
185. Omodei D, Licastro D, Salvatore F, Crosby SD, Fontana L. Serum from humans on long term calorie restriction enhances stress resistance in cell culture. Aging 5: 599-606, 2013.
186. Onodera A, Yanase S, Ishii T, Yasuda K, Miyazawa M, Hartman PS, Ishii N. Post-dauer life span of Caenorhabditis elegans dauer larvae can be modified by Xirradiation. J Radiat Res 51: 67-71, 2010.
187. Partridge L and Gems D. Mechanisms of aging: public or private? Nat Rev Genet 3: 165-175, 2002.
188. Partridge L and Gems D. Benchmarks for aging studies. Nature 450: 165-167, 2007.
189. Partridge L, Pletcher SD, Mair W. Dietary restriction, mortality trajectories, risk and damage. Mech Aging Dev 126: 35-41, 2005.
190. Paulsen G, Cumming KT, Holden G, Hallen J, Ronnestad BR, Sveen O, Skaug A, Paur I, Bastani NE, Ostgaard HN, Buer C, Midttun M, Freuchen F, Wiig H, Ulseth ET, Garthe I, Blomhoff R, Benestad HB, Raastad T. Vitamin C and E supplementation hampers cellular adaptation to endurance training in humans: a double-blind randomized controlled trial. J Physiol 592: 1887-1901, 2014.
191. Perez VI, Bokov A, Van Remmen H, Mele J, Ran Q, Ikeno Y, Richardson A. Is the oxidative stress theory of aging dead? Biochim Biophys Acta 1790: 1005-1014, 2009.
192. Perez VI, Lew CM, Cortez LA, Webb CR, Rodriguez M, Liu Y, Qi W, Li Y, Chaudhuri A, Van Remmen H, Richardson A, Ikeno Y. Thioredoxin 2 haploinsufficiency in mice results in impaired mitochondrial function and increased oxidative stress. Free Radic Biol Med 44: 882-892, 2008.
193. Petriv OI and Rachubinski RA. Lack of peroxisomal catalase causes a progeric phenotype in Caenorhabditis elegans. J Biol Chem 279: 19996-20001, 2004.
194. Pletcher SD, Khazaeli AA, Curtsinger JW. Why do life spans differ? Partitioning mean longevity differences in terms of age-specific mortality parameters. J Gerontol A Biol Sci Med Sci 55: B381-B389, 2000.
195. Poovathingal SK, Gruber J, Lakshmanan L, Halliwell B, Gunawan R. Is mitochondrial DNA turnover slower than commonly assumed? Biogerontology 13: 557-564, 2012.
196. Powers SK, Nelson WB, Hudson MB. Exerciseinduced oxidative stress in humans: cause and consequences. Free Radic Biol Med 51: 942-950, 2011.
197. Pradel E, Zhang Y, Pujol N, Matsuyama T, Bargmann CI, Ewbank JJ. Detection and avoidance of a natural product from the pathogenic bacterium Serratia marcescens by Caenorhabditis elegans. Proc Natl Acad Sci USA 104: 2295-2300, 2007.
198. Pujol N, Link EM, Liu LX, Kurz CL, Alloing G, Tan MW, Ray KP, Solari R, Johnson CD, Ewbank JJ. A reverse genetic analysis of components of the Toll signaling pathway in Caenorhabditis elegans. Curr Biol 11: 809-821, 2001.
199. Pujol N, Zugasti O, Wong D, Couillault C, Kurz CL, Schulenburg H, Ewbank JJ. Anti-fungal innate immunity in C. elegans is enhanced by evolutionary diversification of antimicrobial peptides. PLoS Pathogens 4: e1000105, 2008.
200. Pun PB, Gruber J, Tang SY, Schaffer S, Ong RL, Fong S, Ng LF, Cheah I, Halliwell B. Aging in nematodes: do antioxidants extend lifespan in Caenorhabditis elegans? Biogerontology 11: 17-30, 2010.
201. Radyuk SN, Klichko VI, Michalak K, Orr WC. The effect of peroxiredoxin 4 on fly physiology is a complex interplay of antioxidant and signaling functions. FASEB J 27: 1426-1438, 2013.
202. Radyuk SN, Rebrin I, Klichko VI, Sohal BH, Michalak K, Benes J, Sohal RS, Orr WC. Mitochondrial peroxiredoxins are critical for the maintenance of redox state and the survival of adult Drosophila. Free Radic Biol Med 49: 1892-1902, 2010.
203. Ranjan M, Gruber J, Ng LF, Halliwell B. Repression of the mitochondrial peroxiredoxin antioxidant system does not shorten life span but causes reduced fitness in Caenorhabditis elegans. Free Radic Biol Med 63: 381-389, 2013.
204. Rattan SI. Hormesis in aging. Aging Res Rev 7: 63-78, 2008.
205. Rattan SI, Kryzch V, Schnebert S, Perrier E, Nizard C. Hormesis-based anti-aging products: a case study of a novel cosmetic. Dose Response 11: 99-108, 2013.
206. Rattan SS and Demirovic D. Hormesis as a Mechanism for the Anti-Aging Effects of Calorie Restriction. In: Calorie Restriction, Aging and Longevity, edited by Everitt AV, Rattan SIS, le Couteur DG, de Cabo R. Netherlands: Springer, 2010, pp. 233-245.
207. Reuben DB, Cheh AI, Harris TB, Ferrucci L, Rowe JW, Tracy RP, Seeman TE. Peripheral blood markers of inflammation predict mortality and functional decline in high-functioning community-dwelling older persons. J Am Geriatr Soc 50: 638-644, 2002.
208. Rhee SG, Woo HA, Kil IS, Bae SH. Peroxiredoxin functions as a peroxidase and a regulator and sensor of local peroxides. J Biol Chem 287: 4403-4410, 2012.
209. Rice TW, Wheeler AP, Thompson BT, deBoisblanc BP, Steingrub J, Rock P. Enteral omega-3 fatty acid, gamma-linolenic acid, antioxidant supplementation in acute lung injury. JAMA 306: 1574-1581, 2011.
210. Ristow M and Schmeisser K. Mitohormesis: promoting health and lifespan by increased levels of reactive oxygen species (ROS). Dose Response 12: 288-341, 2014.
211. Ristow M and Schmeisser S. Extending life span by increasing oxidative stress. Free Radic Biol Med 51: 327-336, 2011.
212. Ristow M and Zarse K. How increased oxidative stress promotes longevity and metabolic health: the concept of mitochondrial hormesis (mitohormesis). Exp Gerontol 45: 410-418, 2010.
213. Ristow M, Zarse K, Oberbach A, Kloting N, Birringer M, Kiehntopf M, Stumvoll M, Kahn CR, Bluher M. Antioxidants prevent health-promoting effects of physical exercise in humans. Proc Natl Acad Sci USA 106: 8665-8670, 2009.
214. Rothman SM and Mattson MP. Activity-dependent, stress-responsive BDNF signaling and the quest for optimal brain health and resilience throughout the lifespan. Neuroscience 239: 228-240, 2013.
215. Rotig A, Bourgeron T, Chretien D, Rustin P, Munnich A. Spectrum of mitochondrial DNA rearrangements in the Pearson marrow-pancreas syndrome. Hum Mol Genet 4: 1327-1330, 1995.
216. Rovelet-Lecrux A, Hannequin D, Raux G, Le Meur N, Laquerriere A, Vital A, Dumanchin C, Feuillette S, Brice A, Vercelletto M, Dubas F, Frebourg T, Campion D. APP locus duplication causes autosomal dominant earlyonset Alzheimer disease with cerebral amyloid angiopathy. Nat Genet 38: 24-26, 2006.
217. Sakashita T, Takanami T, Yanase S, Hamada N, Suzuki M, Kimura T, Kobayashi Y, Ishii N, Higashitani A. Radiation biology of Caenorhabditis elegans: germ cell response, aging and behavior. J Radiat Res 51: 107-121, 2010.
218. Saul N, Pietsch K, Sturzenbaum SR, Menzel R, Steinberg CE. Hormesis and longevity with tannins: free of charge or cost-intensive? Chemosphere 93: 1005-1008, 2013.
219. Sawin ER, Ranganathan R, Horvitz HR. C. elegans locomotory rate is modulated by the environment through a dopaminergic pathway and by experience through a serotonergic pathway. Neuron 26: 619-631, 2000.
220. Schmeisser S, Schmeisser K, Weimer S, Groth M, Priebe S, Fazius E, Kuhlow D, Pick D, Einax JW, Guthke R, Platzer M, Zarse K, Ristow M. Mitochondrial hormesis links low-dose arsenite exposure to lifespan extension. Aging Cell 12: 508-517, 2013.
221. Schmeisser S, Zarse K, Ristow M. Lonidamine extends lifespan of adult Caenorhabditis elegans by increasing the formation of mitochondrial reactive oxygen species. Horm Metab Res 43: 687-692, 2011.
222. Schmitt K, Grimm A, Kazmierczak A, Strosznajder JB, Gotz J, Eckert A. Insights into mitochondrial dysfunction: aging, amyloid-beta, tau-A deleterious trio. Antioxid Redox Signal 16: 1456-1466, 2012.
223. Schriner SE and Linford NJ. Extension of mouse lifespan by overexpression of catalase. Age (Dordr) 28: 209-218, 2006.
224. Schriner SE, Linford NJ, Martin GM, Treuting P, Ogburn CE, Emond M, Coskun PE, Ladiges W, Wolf N, Van Remmen H, Wallace DC, Rabinovitch PS. Extension of murine life span by overexpression of catalase targeted to mitochondria. Science 308: 1909-1911, 2005.
225. Schroder K and Tschopp J. The inflammasomes. Cell 140: 821-832, 2010.
226. Schulenburg H and Ewbank JJ. The genetics of pathogen avoidance in Caenorhabditis elegans. Mol Microbiol 66: 563-570, 2007.
227. Seok J, Warren HS, Cuenca AG, Mindrinos MN, Baker HV, Xu W, Richards DR, McDonald-Smith GP, Gao H, Hennessy L, Finnerty CC, Lopez CM, Honari S, Moore EE, Minei JP, Cuschieri J, Bankey PE, Johnson JL, Sperry J, Nathens AB, Billiar TR, West MA, Jeschke MG, Klein MB, Gamelli RL, Gibran NS, Brownstein BH, Miller-Graziano C, Calvano SE, Mason PH, Cobb JP, Rahme LG, Lowry SF, Maier RV, Moldawer LL, Herndon DN, Davis RW, Xiao W, Tompkins RG; Inflammation, Host Response to Injury LSCRP. Genomic responses in mouse models poorly mimic human inflammatory diseases. Proc Natl Acad Sci USA 110: 3507-3512, 2013.
228. 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 103: 14086-14091, 2006.
229. Sifri CD, Begun J, Ausubel FM, Calderwood SB. Caenorhabditis elegans as a model host for Staphylococcus aureus pathogenesis. Infect Immun 71: 2208-2217, 2003.
230. Silverman GA, Luke CJ, Bhatia SR, Long OS, Vetica AC, Perlmutter DH, Pak SC. Modeling molecular and cellular aspects of human disease using the nematode Caenorhabditis elegans. Pediatr Res 65: 10-18, 2009.
231. Sinclair DA and Guarente L. Extrachromosomal rDNA circles-a cause of aging in yeast. Cell 91: 1033-1042, 1997.
232. Singh V and Aballay A. Regulation of DAF-16-mediated innate immunity in Caenorhabditis elegans. J Biol Chem 284: 35580-35587, 2009.
233. Sleegers K, Brouwers N, Gijselinck I, Theuns J, Goossens D, Wauters J, Del-Favero J, Cruts M, van Duijn CM, Van Broeckhoven C. APP duplication is sufficient to cause early onset Alzheimer's dementia with cerebral amyloid angiopathy. Brain 129: 2977-2983, 2006.
234. Smith JV and Luo Y. Elevation of oxidative free radicals in Alzheimer's disease models can be attenuated by Ginkgo biloba extract EGb 761. J Alzheimers Dis 5: 287-300, 2003.
235. Snoeks L, Weber CR, Turner JR, Bhattacharyya M, Wasland K, Savkovic SD. Tumor suppressor Foxo3a is involved in the regulation of lipopolysaccharideinduced interleukin-8 in intestinal HT-29 cells. Infect Immun 76: 4677-4685, 2008.
236. Son TG, Camandola S, Mattson MP. Hormetic dietary phytochemicals. Neuro Mol Med 10: 236-246, 2008.
237. Stein GM and Murphy CT. The intersection of aging, longevity pathways, learning and memory in C. elegans. Front Genet 3: 259, 2012.
238. Stiernagle T. Maintenance of C. elegans. Wormbook 11: 1-11, 2006.
239. Stranahan AM and Mattson MP. Recruiting adaptive cellular stress responses for successful brain aging. Nat Rev Neurosci 13: 209-216, 2012.
240. Stuart JA, Maddalena LA, Merilovich M, Robb EL. A midlife crisis for the mitochondrial free radical theory of aging. Longev Healthspan 3: 4, 2014.
241. Sulston JE and Horvitz HR. Post-embryonic cell lineages of the nematode, Caenorhabditis elegans. Dev Biol 56: 110-156, 1977.
242. Sulston JE, Schierenberg E, White JG, Thomson JN. The embryonic cell lineage of the nematode Caenorhabditis elegans. Dev Biol 100: 64-119, 1983.
243. Suzuki N, Inokuma K, Yasuda K, Ishii N. Cloning, sequencing and mapping of a manganese superoxide dismutase gene of the nematode Caenorhabditis elegans. DNA Res 3: 171-174, 1996.
244. Taylor RW and Turnbull DM. Mitochondrial DNA mutations in human disease. Nat Rev Genet 6: 389-402, 2005.
245. Tenor JL and Aballay A. A conserved Toll-like receptor is required for Caenorhabditis elegans innate immunity. EMBO Rep 9: 103-109, 2008.
246. Testa G, Biasi F, Poli G, Chiarpotto E. Calorie restriction and dietary restriction mimetics: a strategy for improving healthy aging and longevity. Curr Pharm Des 20: 2950-2977, 2014.
247. Treusch S, Hamamichi S, Goodman JL, Matlack KE, Chung CY, Baru V, Shulman JM, Parrado A, Bevis BJ, Valastyan JS, Han H, Lindhagen-Persson M, Reiman EM, Evans DA, Bennett DA, Olofsson A, DeJager PL, Tanzi RE, Caldwell KA, Caldwell GA, Lindquist S. Functional links between Abeta toxicity, endocytic trafficking, Alzheimer's disease risk factors in yeast. Science 334: 1241-1245, 2011.
248. Treuting PM, Linford NJ, Knoblaugh SE, Emond MJ, Morton JF, Martin GM, Rabinovitch PS, Ladiges WC. Reduction of age-associated pathology in old mice by overexpression of catalase in mitochondria. J Gerontol A Biol Sci Med Sci 63: 813-822, 2008.
249. Tullet JM, Araiz C, Sanders MJ, Au C, Benedetto A, Papatheodorou I, Clark E, Schmeisser K, Jones D, Schuster EF, Thornton JM, Gems D. DAF-16/FoxO directly regulates an atypical AMP-activated protein kinase gamma isoform to mediate the effects of insulin/IGF-1 signaling on aging in Caenorhabditis elegans. PLoS Genet 10: e1004109, 2014.
250. Van Raamsdonk JM and Hekimi S. Deletion of the mitochondrial superoxide dismutase sod-2 extends lifespan in Caenorhabditis elegans. PLoS Genet 5: e1000361, 2009.
251. Van Raamsdonk JM and Hekimi S. Reactive oxygen species and aging in Caenorhabditis elegans: causal or casual relationship? Antioxid Redox Signal 13: 1911-1953, 2010.
252. Van Raamsdonk JM and Hekimi S. Superoxide dismutase is dispensable for normal animal lifespan. Proc Natl Acad Sci USA 109: 5785-5790, 2012.
253. Van Remmen H, Ikeno Y, Hamilton M, Pahlavani M, Wolf N, Thorpe SR, Alderson NL, Baynes JW, Epstein CJ, Huang TT, Nelson J, Strong R, Richardson A. Life-long reduction in MnSOD activity results in increased DNA damage and higher incidence of cancer but does not accelerate aging. Physiol Genomics 16: 29-37, 2003.
254. Van Voorhies WA, Fuchs J, Thomas S. The longevity of Caenorhabditis elegans in soil. Biol Lett 1: 247-249, 2005.
255. Ved R, Saha S, Westlund B, Perier C, Burnam L, Sluder A, Hoener M, Rodrigues CM, Alfonso A, Steer C, Liu L, Przedborski S, Wolozin B. Similar patterns of mitochondrial vulnerability and rescue induced by genetic modification of alpha-synuclein, parkin, DJ-1 in Caenorhabditis elegans. J Biol Chem 280: 42655-42668, 2005.
256. Verdoucq L. In vivo characterization of a thioredoxin h target protein defines a new peroxiredoxin family. J Biol Chem 274: 19714-19722, 1999.
257. Wang D, Liu P, Xing X. Pre-treatment with mild UV irradiation increases the resistance of nematode Caenorhabditis elegans to toxicity on locomotion behaviors from metal exposure. Environ Toxicol Pharmacol 29: 213-222, 2010.
258. Watabe S, Hasegawa H, Takimoto K, Yamamoto Y, Takahashi SY. Possible function of SP-22, a substrate of mitochondrial ATP-dependent protease, as a radical scavenger. Biochem Biophys Res Commun 213: 1010-1016, 1995.
259. Weimer S, Priebs J, Kuhlow D, Groth M, Priebe S, Mansfeld J, Merry TL, Dubuis S, Laube B, Pfeiffer AF, Schulz TJ, Guthke R, Platzer M, Zamboni N, Zarse K, Ristow M. D-Glucosamine supplementation extends life span of nematodes and of aging mice. Nat Commun 5: 3563, 2014.
260. White JG, Southgate E, Thomson JN, Brenner S. The structure of the nervous system of the nematode Caenorhabditis elegans. Philos Trans R Soc Lond B Biol Sci 314: 1-340, 1986.
261. Wolozin B, Gabel C, Ferree A, Guillily M, Ebata A. Watching worms whither: modeling neurodegeneration in C. elegans. Prog Mol Biol Transl Sci 100: 499-514, 2011.
262. Wszolek ZK, Tsuboi Y, Ghetti B, Pickering-Brown S, Baba Y, Cheshire WP. Frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). Orphanet J Rare Dis 1: 30, 2006.
263. Wu D, Cypser JR, Yashin AI, Johnson TE. Multiple mild heat-shocks decrease the Gompertz component of mortality in Caenorhabditis elegans. Exp Gerontol 44: 607-612, 2009.
264. Wu D, Rea SL, Cypser JR, Johnson TE. Mortality shifts in Caenorhabditis elegans: remembrance of conditions past. Aging Cell 8: 666-675, 2009.
265. Wu Y and Luo Y. Transgenic C. elegans as a model in Alzheimer's research. Curr Alzheimer Res 2: 37-45, 2005.
266. Wu Y, Wu Z, Butko P, Christen Y, Lambert MP, Klein WL, Link CD, Luo Y. Amyloid-beta-induced pathological behaviors are suppressed by Ginkgo biloba extract EGb 761 and ginkgolides in transgenic Caenorhabditis elegans. J Neurosci 26: 13102-13113, 2006.
267. Yamashita S, Nishino I, Nonaka I, Goto YI. Genotype and phenotype analyses in 136 patients with single largescale mitochondrial DNA deletions. J Hum Genet 53: 598-606, 2008.
268. Yang W, Li J, Hekimi S. A measurable increase in oxidative damage due to reduction in superoxide detoxification fails to shorten the life span of long-lived mitochondrial mutants of Caenorhabditis elegans. Genetics 177: 2063-2074, 2007.
269. Yanowitz J and Fire A. Cyclin D involvement demarcates a late transition in C. elegans embryogenesis. Dev Biol 279: 244-251, 2005.
270. Yatin SM, Varadarajan S, Link CD, Butterfield DA. In vitro and in vivo oxidative stress associated with Alzheimer's amyloid beta-peptide (1-42). Neurobiol Aging 20: 325-330; discussion 339-342, 1999.
271. Yuan J and Horvitz HR. The Caenorhabditis elegans cell death gene ced-4 encodes a novel protein and is expressed during the period of extensive programmed cell death. Development 116: 309-320, 1992.
272. Yuan J, Shaham S, Ledoux S, Ellis HM, Horvitz HR. The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1 beta-converting enzyme. Cell 75: 641-652, 1993.
273. Yun J and Finkel T. Mitohormesis. Cell Metab 19: 757-766, 2014.
274. Zahedi Avval F and Holmgren A. Molecular mechanisms of thioredoxin and glutaredoxin as hydrogen donors for Mammalian S phase ribonucleotide reductase. J Biol Chem 284: 8233-8240, 2009.
275. Zarse K, Bossecker A, Muller-Kuhrt L, Siems K, Hernandez MA, Berendsohn WG, Birringer M, Ristow M. The phytochemical glaucarubinone promotes mitochondrial metabolism, reduces body fat, extends lifespan of Caenorhabditis elegans. Horm Metab Res 43: 241-243, 2011.
276. Zaveri NT. Green tea and its polyphenolic catechins: medicinal uses in cancer and noncancer applications. Life Sci 78: 2073-2080, 2006.