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Role of Oxidative Stress in Aging

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Abstract

The question of why we age has given rise to many different theories over the last decades. One of the most popular and long-lasting hypothesis is the free radical theory of aging. It postulates that endogenously generated reactive oxygen species (ROS) accumulate over time, causing damage to cellular macromolecules and eventually leading to physiological decline, disease, aging, and death. Over the years, a multitude of correlative evidence has been collected in favor of this aging theory, including the discovery that aging and many age-related diseases are accompanied by substantial cellular oxidative damage. However, genetic manipulation of components of cellular antioxidant defense systems in model organisms, like Caenorhabditis elegans, Drosophila melanogaster or mice have generated conflicting results and suggested a more complex interplay between endogenous oxidants, antioxidants, and lifespan. The fact that ROS play important roles as second messengers in signaling processes, in hormesis, and during the oxidative burst in innate immune cells, likely contributes to the complexity of this issue. In this chapter, we present an overview of the most crucial experiments conducted to address the free radical theory of aging. Our conclusion is that ROS are major players involved in lifespan and aging but likely not (only) in their role as cytotoxic agents but as regulators of essential physiological processes in the cell.

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References

  • Andziak B, O’Connor TP, Buffenstein R (2005) Antioxidants do not explain the disparate longevity between mice and the longest-living rodent, the naked mole-rat. Mech Ageing Dev 126:1206–1212

    CAS  PubMed  Google Scholar 

  • Ash CE, Merry BJ (2011) The molecular basis by which dietary restricted feeding reduces mitochondrial reactive oxygen species generation. Mech Ageing Dev 132:43–54

    CAS  PubMed  Google Scholar 

  • Asikainen TM, Huang TT, Taskinen E, Levonen AL, Carlson E, Lapatto R, Epstein CJ, Raivio KO (2002) Increased sensitivity of homozygous Sod2 mutant mice to oxygen toxicity. Free Radic Biol Med 32:175–186

    CAS  PubMed  Google Scholar 

  • Ayyadevara S, Dandapat A, Singh SP, Benes H, Zimniak L, Reis RJS, Zimniak P (2005) Lifespan extension in hypomorphic daf-2 mutants of Caenorhabditis elegans is partially mediated by glutathione transferase CeGSTP2-2. Aging Cell 4:299–307

    CAS  PubMed  Google Scholar 

  • Back P, de Vos WH, Depuydt GG, Matthijssens F, Vanfleteren JR, Braeckman BP (2012) Exploring real-time in vivo redox biology of developing and aging Caenorhabditis elegans. Free Radic Biol Med 52:850–859

    CAS  PubMed  Google Scholar 

  • Barnham KJ, Masters CL, Bush AI (2004) Neurodegenerative diseases and oxidative stress. Nat Rev Drug Discov 3:205–214

    CAS  PubMed  Google Scholar 

  • Barros MH, Bandy B, Tahara EB, Kowaltowski AJ (2004) Higher respiratory activity decreases mitochondrial reactive oxygen release and increases life span in Saccharomyces cerevisiae. J Biol Chem 279:49883–49888

    CAS  PubMed  Google Scholar 

  • Bayne ACV, Mockett RJ, Orr WC, Sohal RS (2005) Enhanced catabolism of mitochondrial superoxide/hydrogen peroxide and aging in transgenic Drosophila. Biochem J 391:277–284

    CAS  PubMed  Google Scholar 

  • Bedard K, Krause KH (2007) The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev 87:245–313

    CAS  PubMed  Google Scholar 

  • Bevilacqua L, Ramsey JJ, Hagopian K, Weindruch R, Harper ME (2004) Effects of short- and medium-term calorie restriction on muscle mitochondrial proton leak and reactive oxygen species production. Am J Physiol Endocrinol Metab 286:E852–E861

    CAS  PubMed  Google Scholar 

  • Bluher M, Kahn BB, Kahn CR (2003) Extended longevity in mice lacking the insulin receptor in adipose tissue. Science 299:572–574

    PubMed  Google Scholar 

  • Bortolato M, Chen K, Shih JC (2008) Monoamine oxidase inactivation: from pathophysiology to therapeutics. Adv Drug Deliv Rev 60:1527–1533

    CAS  PubMed Central  PubMed  Google Scholar 

  • Brandes N, Schmitt S, Jakob U (2009) Thiol-based redox switches in eukaryotic proteins. Antioxid Redox Signal 11:997–1014

    CAS  PubMed  Google Scholar 

  • Brandes N, Reichmann D, Tienson H, Leichere LI, Jakob U (2011) Using quantitative redox proteomics to dissect the yeast redoxome. J Biol Chem 286:41893–41903

    CAS  PubMed  Google Scholar 

  • Brys K, Vanfleteren JR, Braeckman BP (2007) Testing the rate-of-living/oxidative damage theory of aging in the nematode model Caenorhabditis elegans. Exp Gerontol 42:845–851

    CAS  PubMed  Google Scholar 

  • Cabreiro F, Ackerman D, Doonan R, Araiz C, Back P, Papp D, Braeckman BP, Gems D (2011) 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

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cadenas E, Davies KJA (2000) Mitochondrial free radical generation, oxidative stress, and aging. Free Radic Biol Med 29:222–230

    CAS  PubMed  Google Scholar 

  • Carlsson LM, Jonsson J, Edlund T, Marklund SL (1995) Mice lacking extracellular superoxide dismutase are more sensitive to hyperoxia. Proc Natl Acad Sci USA 92:6264–6268

    CAS  PubMed  Google Scholar 

  • Ceriello A, Motz E (2004) Is oxidative stress the pathogenic mechanism underlying insulin resistance, diabetes, and cardiovascular disease? The common soil hypothesis revisited. Arterioscler Thromb Vasc Biol 24:816–823

    CAS  PubMed  Google Scholar 

  • Chance B, Williams GR (1956) The respiratory chain and oxidative phosphorylation. Adv Enzymol Relat Subj Biochem 17:65–134

    CAS  PubMed  Google Scholar 

  • Chen XL, Mele J, Giese H, van Remmen H, Dolle MET, Steinhelper M, Richardson A, Vijg J (2003) A strategy for the ubiquitous overexpression of human catalase and CuZn superoxide dismutase genes in transgenic mice. Mech Ageing Dev 124:219–227

    CAS  PubMed  Google Scholar 

  • Cho CG, Kim HJ, Chung SW, Jung KJ, Shim KH, Yu BP, Yodoi J, Chung HY (2003) Modulation of glutathione and thioredoxin systems by calorie restriction during the aging process. Exp Gerontol 38:539–548

    CAS  PubMed  Google Scholar 

  • Cocheme HM, Quin C, McQuaker SJ, Cabreiro F, Logan A, Prime TA, Abakumova I, Patel JV, Fearnley IM, James AM, Porteous CM, Smith RAJ, Saeed S, Carre JE, Singer M, Gems D, Hartley RC, Partridge L, Murphy MP (2011) Measurement of H(2)O(2) within living Drosophila during aging using a ratiometric mass spectrometry probe targeted to the mitochondrial matrix. Cell Metab 13:340–350

    CAS  PubMed  Google Scholar 

  • Collet JF, Messens J (2010) Structure, function, and mechanism of thioredoxin proteins. Antioxid Redox Signal 13:1205–1216

    CAS  PubMed  Google Scholar 

  • Copeland JM, Cho J, Lo T Jr, Hur JH, Bahadorani S, Arabyan T, Rabie J, Soh J, Walker DW (2009) Extension of Drosophila life span by RNAi of the mitochondrial respiratory chain. Curr Biol 19:1591–1598

    CAS  PubMed  Google Scholar 

  • D’Autreaux B, Toledano MB (2007) ROS as signalling molecules: mechanisms that generate specificity in ROS homeostasis. Nat Rev Mol Cell Biol 8:813–824

    PubMed  Google Scholar 

  • Dalle-Donne I, Rossi R, Giustarini D, Milzani A, Colombo R (2003) Protein carbonyl groups as biomarkers of oxidative stress. Clin Chim Acta 329:23–38

    CAS  PubMed  Google Scholar 

  • Dillin A, Hsu AL, Arantes-Oliveira NA, Lehrer-Graiwer J, Hsin H, Fraser AG, Kamath RS, Ahringer J, Kenyon C (2002) Rates of behavior and aging specified by mitochondrial function during development. Science 298:2398–2401

    CAS  PubMed  Google Scholar 

  • Doonan R, McElwee JJ, Matthijssens F, Walker GA, Houthoofd K, Back P, Matscheski A, Vanfleteren JR, Gems D (2008) 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

    CAS  PubMed  Google Scholar 

  • Droge W (2002) Free radicals in the physiological control of cell function. Physiol Rev 82:47–95

    CAS  PubMed  Google Scholar 

  • Dubey A, Forster MJ, Lal H, Sohal RS (1996) Effect of age and caloric intake on protein oxidation in different brain regions and on behavioral functions of the mouse. Arch Biochem Biophys 333:189–197

    CAS  PubMed  Google Scholar 

  • Dupuy C, Virion A, Ohayon R, Kaniewski J, Deme D, Pommier J (1991) Mechanism of hydrogen-peroxide formation catalyzed by nadph oxidase in thyroid plasma-membrane. J Biol Chem 266:3739–3743

    CAS  PubMed  Google Scholar 

  • Durieux J, Wolff S, Dillin A (2011) The cell-non-autonomous nature of electron transport chain-mediated longevity. Cell 144:79–91

    CAS  PubMed Central  PubMed  Google Scholar 

  • Durusoy M, Diril N, Bozcuk AN (1995) Age-related activity of catalase in different genotypes of Drosophila-melanogaster. Exp Gerontol 30:77–86

    CAS  PubMed  Google Scholar 

  • Duttaroy A, Paul A, Kundu M, Belton A (2003) A Sod2 null mutation confers severely reduced adult life span in Drosophila. Genetics 165:2295–2299

    CAS  PubMed  Google Scholar 

  • Elchuri S, Oberley TD, Qi W, Eisenstein RS, Jackson Roberts L, Van Remmen H, Epstein CJ, Huang TT (2005) CuZnSOD deficiency leads to persistent and widespread oxidative damage and hepatocarcinogenesis later in life. Oncogene 24:367–380

    CAS  PubMed  Google Scholar 

  • Feng JL, Bussiere F, Hekimi S (2001) Mitochondrial electron transport is a key determinant of life span in Caenorhabditis elegans. Dev Cell 1:633–644

    CAS  PubMed  Google Scholar 

  • Finkel T (2011a) Signal transduction by mitochondrial oxidants. J Biol Chem 287(7):4434–4440

    PubMed  Google Scholar 

  • Finkel T (2011b) Signal transduction by reactive oxygen species. J Cell Biol 194:7–15

    CAS  PubMed  Google Scholar 

  • Finkel T, Holbrook NJ (2000) Oxidants, oxidative stress and the biology of ageing. Nature 408:239–247

    CAS  PubMed  Google Scholar 

  • Fontana L, Partridge L, Longo VD (2010) Extending healthy life span-from yeast to humans. Science 328:321–326

    CAS  PubMed Central  PubMed  Google Scholar 

  • Fridovic I (1972) Superoxide radical and superoxide dismutase. Acc Chem Res 5:321–326

    Google Scholar 

  • Fu YX, Cheng WH, Ross DA, Lei XG (1999) Cellular glutathione peroxidase protects mice against lethal oxidative stress induced by various doses of diquat. Proc Soc Exp Biol Med 222:164–169

    CAS  PubMed  Google Scholar 

  • Ghezzi P, Bonetto V, Fratelli M (2005) Thiol-disulfide balance: from the concept of oxidative stress to that of redox regulation. Antioxid Redox Signal 7:964–972

    CAS  PubMed  Google Scholar 

  • Giannakou ME, Partridge L (2007) Role of insulin-like signalling in Drosophila lifespan. Trends Biochem Sci 32:180–188

    CAS  PubMed  Google Scholar 

  • Giorgio M, Trinei M, Migliaccio E, Pelicci PG (2007) Hydrogen peroxide: a metabolic by-product or a common mediator of ageing signals? Nat Rev Mol Cell Biol 8:722–728

    CAS  PubMed  Google Scholar 

  • Godon C, Lagniel G, Lee J, Buhler JM, Kieffer S, Perrot M, Boucherie H, Toledano MB, Labarre J (1998) The H2O2 stimulon in Saccharomyces cerevisiae. J Biol Chem 273:22480–22489

    CAS  PubMed  Google Scholar 

  • Golden TR, Hinerfeld DA, Melov S (2002) Oxidative stress and aging: beyond correlation. Aging Cell 1:117–123

    CAS  PubMed  Google Scholar 

  • Grant CM (2008) Metabolic reconfiguration is a regulated response to oxidative stress. J Biol 7:1

    PubMed Central  PubMed  Google Scholar 

  • Griswold CM, Matthews AL, Bewley KE, Mahaffey JW (1993) Molecular characterization and rescue of acatalasemic mutants of Drosophila-melanogaster. Genetics 134:781–788

    CAS  PubMed  Google Scholar 

  • Hamanaka RB, Chandel NS (2010) Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes. Trends Biochem Sci 35:505–513

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hansen RE, Roth D, Winther JR (2009) Quantifying the global cellular thiol-disulfide status. Proc Natl Acad Sci USA 106:422–427

    CAS  PubMed  Google Scholar 

  • Harman D (1956) Aging – a theory based on free-radical and radiation-chemistry. J Gerontol 11:298–300

    CAS  PubMed  Google Scholar 

  • Harman D (1972) Biologic clock – mitochondria. J Am Geriatr Soc 20:145–147

    CAS  PubMed  Google Scholar 

  • Hartman PS, Ishii N, Kayser EB, Morgan PG, Sedensky MM (2001) Mitochondrial mutations differentially affect aging, mutability and anesthetic sensitivity in Caenorhabditis elegans. Mech Ageing Dev 122:1187–1201

    CAS  PubMed  Google Scholar 

  • Heidler T, Hartwig K, Daniel H, Wenzel U (2010) Caenorhabditis elegans lifespan extension caused by treatment with an orally active ROS-generator is dependent on DAF-16 and SIR-2.1. Biogerontology 11:183–195

    CAS  PubMed  Google Scholar 

  • Heilbronn LK, Ravussin E (2003) Calorie restriction and aging: review of the literature and implications for studies in humans. Am J Clin Nutr 78:361–369

    CAS  PubMed  Google Scholar 

  • Hernandez-Garcia D, Wood CD, Castro-Obregon S, Covarrubias L (2010) Reactive oxygen species: a radical role in development? Free Radic Biol Med 49:130–143

    CAS  PubMed  Google Scholar 

  • Ho YS, Magnenat JL, Bronson RT, Cao J, Gargano M, Sugawara M, Funk CD (1997) Mice deficient in cellular glutathione peroxidase develop normally and show no increased sensitivity to hyperoxia. J Biol Chem 272:16644–16651

    CAS  PubMed  Google Scholar 

  • Ho YS, Xiong Y, Ma WC, Spector A, Ho DS (2004) Mice lacking catalase develop normally but show differential sensitivity to oxidant tissue injury. J Biol Chem 279:32804–32812

    CAS  PubMed  Google Scholar 

  • Ho HY, Cheng ML, Chiu DT (2007) Glucose-6-phosphate dehydrogenase–from oxidative stress to cellular functions and degenerative diseases. Redox Rep 12:109–118

    CAS  PubMed  Google Scholar 

  • Holmgren A, Johansson C, Berndt C, Lonn ME, Hudemann C, Lillig CH (2005) Thiol redox control via thioredoxin and glutaredoxin systems. Biochem Soc Trans 33:1375–1377

    CAS  PubMed  Google Scholar 

  • Holzenberger M, Dupont J, Ducos B, Leneuve P, Geloen A, Even PC, Cervera P, le Bouc Y (2003) IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice. Nature 421:182–187

    CAS  PubMed  Google Scholar 

  • Honda Y, Honda S (1999) The daf-2 gene network for longevity regulates oxidative stress resistance and Mn-superoxide dismutase gene expression in Caenorhabditis elegans. FASEB J 13:1385–1393

    CAS  PubMed  Google Scholar 

  • Houthoofd K, Braeckman BP, Lenaerts I, Brys K, de Vreese A, van Eygen S, Vanfleteren JR (2002) Axenic growth up-regulates mass-specific metabolic rate, stress resistance, and extends life span in Caenorhabditis elegans. Exp Gerontol 37:1371–1378

    PubMed  Google Scholar 

  • Houthoofd K, Fidalgo MA, Hoogewijs D, Braeckman BP, Lenaerts I, Brys K, Matthijssens F, de Vreese A, van Eygen S, Munoz MJ, Vanfleteren JR (2005) Metabolism, physiology and stress defense in three aging Ins/IGF-1 mutants of the nematode Caenorhabditis elegans. Aging Cell 4:87–95

    CAS  PubMed  Google Scholar 

  • Huang TT, Carlson EJ, Gillespie AM, Shi Y, Epstein CJ (2000) Ubiquitous overexpression of CuZn superoxide dismutase does not extend life span in mice. J Gerontol A Biol Sci Med Sci 55:B5–B9

    CAS  PubMed  Google Scholar 

  • Huang TT, Carlson EJ, Kozy HM, Mantha S, Goodman SI, Ursell PC, Epstein CJ (2001) Genetic modification of prenatal lethality and dilated cardiomyopathy in Mn superoxide dismutase mutant mice. Free Radic Biol Med 31:1101–1110

    CAS  PubMed  Google Scholar 

  • Ishii N, Takahashi K, Tomita S, Keino T, Honda S, Yoshino K, Suzuki K (1990) A methyl viologen-sensitive mutant of the nematode Caenorhabditis-elegans. Mutat Res 237:165–171

    CAS  PubMed  Google Scholar 

  • Ishii N, Fujii M, Hartman PS, Tsuda M, Yasuda K, Senoo-Matsuda N, Yanase S, Ayusawa D, Suzuki K (1998) A mutation in succinate dehydrogenase cytochrome b causes oxidative stress and ageing in nematodes. Nature 394:694–697

    CAS  PubMed  Google Scholar 

  • Jacob MH, Janner Dda R, Araujo AS, Jahn MP, Kucharski LC, Moraes TB, Dutra Filho CS, Ribeiro MF, Bello-Klein A (2010) Redox imbalance influence in the myocardial Akt activation in aged rats treated with DHEA. Exp Gerontol 45:957–963

    CAS  PubMed  Google Scholar 

  • Jee C, Vanoaica L, Lee J, Park BJ, Ahnn J (2005) Thioredoxin is related to life span regulation and oxidative stress response in Caenorhabditis elegans. Genes Cells 10:1203–1210

    CAS  PubMed  Google Scholar 

  • Johnson TE (1990) Increased life-span of age-1 mutants in Caenorhabditis-elegans and lower gompertz rate of aging. Science 249:908–912

    CAS  PubMed  Google Scholar 

  • Kakihana T, Nagata K, Sitia R (2012) Peroxides and peroxidases in the endoplasmic reticulum: integrating redox homeostasis and oxidative folding. Antioxid Redox Signal 16:763–771

    CAS  PubMed  Google Scholar 

  • Keaney M, Gems D (2003) No increase in lifespan in Caenorhabditis elegans upon treatment with the superoxide dismutase mimetic EUK-8. Free Radic Biol Med 34:277–282

    CAS  PubMed  Google Scholar 

  • Keaney M, Matthijssens F, Sharpe M, Vanfleteren J, Gems D (2004) 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

    CAS  PubMed  Google Scholar 

  • Kenyon C (2005) The plasticity of aging: insights from long-lived mutants. Cell 120:449–460

    CAS  PubMed  Google Scholar 

  • Kenyon C, Chang J, Gensch E, Rudner A, Tabtiang R (1993) A C-Elegans mutant that lives twice as long as wild-type. Nature 366:461–464

    CAS  PubMed  Google Scholar 

  • Kim J, Takahashi M, Shimizu T, Shirasawa T, Kajita M, Kanayama A, Miyamoto Y (2008) Effects of a potent antioxidant, platinum nanoparticle, on the lifespan of Caenorhabditis elegans. Mech Ageing Dev 129:322–331

    CAS  PubMed  Google Scholar 

  • Klichko VI, Radyuk SN, Orr WC (2004) Profiling catalase gene expression in Drosophila melanogaster during development and aging. Arch Insect Biochem Physiol 56:34–50

    CAS  PubMed  Google Scholar 

  • Klotz LO, Sies H (2009) Cellular generation of oxidants: relation to oxidative stress. In: Redox signaling and regulation in biology and medicine. Wiley-VCH, Weinheim, pp 45–61

    Google Scholar 

  • Kohn RR (1971) Effect of antioxidants on life-span of C57bl mice. J Gerontol 26:378–380

    CAS  PubMed  Google Scholar 

  • Kondo M, Senoo-Matsuda N, Yanase S, Ishii T, Hartman PS, Ishii N (2005) Effect of oxidative stress on translocation of DAF-16 in oxygen-sensitive mutants, mev-1 and gas-1 of Caenorhabditis elegans. Mech Ageing Dev 126:637–641

    CAS  PubMed  Google Scholar 

  • Krause KH (2007) Aging: a revisited theory based on free radicals generated by NOX family NADPH oxidases. Exp Gerontol 42:256–262

    CAS  PubMed  Google Scholar 

  • Kumsta C, Thamsen M, Jakob U (2011) Effects of oxidative stress on behavior, physiology, and the redox thiol proteome of Caenorhabditis elegans. Antioxid Redox Signal 14:1023–1037

    CAS  PubMed  Google Scholar 

  • Lambert AJ, Merry BJ (2004) Effect of caloric restriction on mitochondrial reactive oxygen species production and bioenergetics: reversal by insulin. Am J Physiol Regul Integr Comp Physiol 286:R71–R79

    CAS  PubMed  Google Scholar 

  • Lambeth JD (2004) NOX enzymes and the biology of reactive oxygen. Nat Rev Immunol 4:181–189

    CAS  PubMed  Google Scholar 

  • Lapointe J, Hekimi S (2008) Early mitochondrial dysfunction in long-lived Mclk1(+/−) mice. J Biol Chem 283:26217–26227

    CAS  PubMed  Google Scholar 

  • Lee SS, Lee RYN, Fraser AG, Kamath RS, Ahringer J, Ruvkun G (2003a) A systematic RNAi screen identifies a critical role for mitochondria in C-elegans longevity. Nat Genet 33:40–48

    CAS  PubMed  Google Scholar 

  • 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 (2003b) Peroxiredoxin II is essential for sustaining life span of erythrocytes in mice. Blood 101:5033–5038

    CAS  PubMed  Google Scholar 

  • Lee KS, Iijima-Ando K, Iijima K, Lee WJ, Lee JH, Yu K, Lee DS (2009a) JNK/FOXO-mediated neuronal expression of fly homologue of peroxiredoxin II reduces oxidative stress and extends life span. J Biol Chem 284:29454–29461

    CAS  PubMed  Google Scholar 

  • Lee SJ, Murphy CT, Kenyon C (2009b) Glucose shortens the life span of C. elegans by downregulating DAF-16/FOXO activity and aquaporin gene expression. Cell Metab 10:379–391

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lee SJ, Hwang AB, Kenyon C (2010) Inhibition of respiration extends C. elegans life span via reactive oxygen species that increase HIF-1 activity. Curr Biol 20:2131–2136

    CAS  PubMed Central  PubMed  Google Scholar 

  • Levine RL (2002) Carbonyl modified proteins in cellular regulation, aging, and disease. Free Radic Biol Med 32:790–796

    CAS  PubMed  Google Scholar 

  • Li Y, Huang TT, Carlson EJ, Melov S, Ursell PC, Olson JL, Noble LJ, Yoshimura MP, Berger C, Chan PH, Wallace DC, Epstein CJ (1995) Dilated cardiomyopathy and neonatal lethality in mutant mice lacking manganese superoxide dismutase. Nat Genet 11:376–381

    CAS  PubMed  Google Scholar 

  • Lin K, Hsin H, Libina N, Kenyon C (2001) Regulation of the Caenorhabditis elegans longevity protein DAF-16 by insulin/IGF-1 and germline signaling. Nat Genet 28:139–145

    CAS  PubMed  Google Scholar 

  • Lin SJ, Kaeberlein M, Andalis AA, Sturtz LA, Defossez PA, Culotta VC, Fink GR, Guarente L (2002) Calorie restriction extends Saccharomyces cerevisiae lifespan by increasing respiration. Nature 418:344–348

    CAS  PubMed  Google Scholar 

  • Liu XX, Jiang N, Hughes B, Bigras E, Shoubridge E, Hekimi S (2005) Evolutionary conservation of the clk-1-dependent mechanism of longevity: loss of mclk1 increases cellular fitness and lifespan in mice. Genes Dev 19:2424–2434

    CAS  PubMed  Google Scholar 

  • Longo VD, Finch CE (2003) Evolutionary medicine: from dwarf model systems to healthy centenarians? Science 299:1342–1346

    PubMed  Google Scholar 

  • Lopez-Lluch G, Hunt N, Jones B, Zhu M, Jamieson H, Hilmer S, Cascajo MV, Allard J, Ingram DK, Navas P, de Cabo R (2006) Calorie restriction induces mitochondrial biogenesis and bioenergetic efficiency. Proc Natl Acad Sci USA 103:1768–1773

    CAS  PubMed  Google Scholar 

  • Mackay WJ, Bewley GC (1989) The genetics of catalase in Drosophila-melanogaster – isolation and characterization of acatalasemic mutants. Genetics 122:643–652

    CAS  PubMed  Google Scholar 

  • Makino N, Mochizuki Y, Bannai S, Sugita Y (1994) Kinetic studies on the removal of extracellular hydrogen peroxide by cultured fibroblasts. J Biol Chem 269:1020–1025

    CAS  PubMed  Google Scholar 

  • Margittai E, Banhegyi G (2010) Oxidative folding in the endoplasmic reticulum: towards a multiple oxidant hypothesis? FEBS Lett 584:2995–2998

    CAS  PubMed  Google Scholar 

  • Matsui M, Oshima M, Oshima H, Takaku K, Maruyama T, Yodoi J, Taketo MM (1996) Early embryonic lethality caused by targeted disruption of the mouse thioredoxin gene. Dev Biol 178:179–185

    CAS  PubMed  Google Scholar 

  • McCay CM, Crowell MF, Maynard LA (1935) The effect of retarded growth upon the length of life span and upon the ultimate body size. J Nutr 10:63–79

    CAS  Google Scholar 

  • McCord JM, Fridovic I (1969) Superoxide dismutase an enzymic function for erythrocuprein (Hemocuprein). J Biol Chem 244:6049–6055

    CAS  PubMed  Google Scholar 

  • Melov S, Ravenscroft J, Malik S, Gill MS, Walker DW, Clayton PE, Wallace DC, Malfroy B, Doctrow SR, Lithgow GJ (2000) Extension of life-span with superoxide dismutase/catalase mimetics. Science 289:1567–1569

    CAS  PubMed  Google Scholar 

  • Migliaccio E, Giorgio M, Mele S, Pelicci G, Reboidl P, Pandolfi PP, Lanfrancone L, Pelicci PG (1999) The p66(shc) adaptor protein controls oxidative stress response and life span in mammals. Nature 402:309–313

    CAS  PubMed  Google Scholar 

  • Miranda-Vizuete A, Gonzalez JCF, Gahmon G, Burghoorn J, Navas P, Swoboda P (2006) Lifespan decrease in a Caenorhabditis elegans mutant lacking TRX-1, a thioredoxin expressed in ASJ sensory neurons. FEBS Lett 580:484–490

    CAS  PubMed  Google Scholar 

  • Mitsui A, Hamuro J, Nakamura H, Kondo N, Hirabayashi Y, Ishizaki-Koizumi S, Hirakawa T, Inoue T, Yodoi J (2002) Overexpression of human thioredoxin in transgenic mice controls oxidative stress and life span. Antioxid Redox Signal 4:693–696

    CAS  PubMed  Google Scholar 

  • Miwa S, Riyahi K, Partridge L, Brand MD (2004) Lack of correlation between mitochondrial reactive oxygen species production and life span in Drosophila. Strateg Eng Neglig Senescence Why Genuin Control Aging May Be Foreseeable 1019:388–391

    CAS  Google Scholar 

  • Mockett RJ, Orr WC, Rahmandar JJ, Benes JJ, Radyuk SN, Klichko VI, Sohal RS (1999) Overexpression of Mn-containing superoxide dismutase in transgenic Drosophila melanogaster. Arch Biochem Biophys 371:260–269

    CAS  PubMed  Google Scholar 

  • Mockett RJ, Sohal BH, Sohal RS (2010) Expression of multiple copies of mitochondrially targeted catalase or genomic Mn superoxide dismutase transgenes does not extend the life span of Drosophila melanogaster. Free Radic Biol Med 49:2028–2031

    CAS  PubMed Central  PubMed  Google Scholar 

  • Moller IM, Rogowska-Wrzesinska A, Rao RSP (2011) Protein carbonylation and metal-catalyzed protein oxidation in a cellular perspective. J Proteomics 74:2228–2242

    CAS  PubMed  Google Scholar 

  • Muller FL, Song W, Liu Y, Chaudhuri A, Pieke-Dahl S, Strong R, Huang TT, Epstein CJ, Roberts LJ 2nd, Csete M, Faulkner JA, Van Remmen H (2006) Absence of CuZn superoxide dismutase leads to elevated oxidative stress and acceleration of age-dependent skeletal muscle atrophy. Free Radic Biol Med 40:1993–2004

    CAS  PubMed  Google Scholar 

  • Muller FL, Lustgarten MS, Jang Y, Richardson A, van Remmen H (2007) Trends in oxidative aging theories. Free Radic Biol Med 43:477–503

    CAS  PubMed  Google Scholar 

  • Murakami S, Johnson TE (1996) A genetic pathway conferring life extension and resistance to UV stress in Caenorhabditis elegans. Genetics 143:1207–1218

    CAS  PubMed  Google Scholar 

  • Murphy CT (2006) The search for DAF-16/FOXO transcriptional targets: approaches and discoveries. Exp Gerontol 41:910–921

    CAS  PubMed  Google Scholar 

  • Murphy MP (2012) Mitochondrial thiols in antioxidant protection and redox signaling: distinct roles for glutathionylation and other thiol modifications. Antioxid Redox Signal 16:476–495

    CAS  PubMed  Google Scholar 

  • Murphy CT, McCarroll SA, Bargmann CI, Fraser A, Kamath RS, Ahringer J, Li H, Kenyon C (2003) Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans. Nature 424:277–284

    CAS  PubMed  Google Scholar 

  • Nauseef WM (2008) Biological roles for the NOX family NADPH oxidases. J Biol Chem 283:16961–16965

    CAS  PubMed  Google Scholar 

  • Nemoto S, Finkel T (2002) Redox regulation of forkhead proteins through a p66shc-dependent signaling pathway. Science 295:2450–2452

    CAS  PubMed  Google Scholar 

  • Neumann CA, Krause DS, Carman CV, Das S, Dubey DP, Abraham JL, Bronson RT, Fujiwara Y, Orkin SH, van Etten RA (2003) Essential role for the peroxiredoxin Prdx1 in erythrocyte antioxidant defence and tumour suppression. Nature 424:561–565

    CAS  PubMed  Google Scholar 

  • Nicholls P, Fita I, Loewen PC (2001) Enzymology and structure of catalases. Adv Inorg Chem 51(51):51–106

    CAS  Google Scholar 

  • Niki E (1987) Interaction of ascorbate and alpha-tocopherol. Ann N Y Acad Sci 498:186–199

    CAS  PubMed  Google Scholar 

  • Nisoli E, Tonetto C, Cardile A, Cozzi V, Bracale R, Tedesco L, Falcone S, Valerio A, Cantoni O, Clementi E, Moncada S, Carruba MO (2005) Calorie restriction promotes mitochondrial biogenesis by inducing the expression of eNOS. Science 310:314–317

    CAS  PubMed  Google Scholar 

  • Nonn L, Williams RR, Erickson RP, Powis G (2003) The absence of mitochondrial thioredoxin 2 causes massive apoptosis, exencephaly, and early embryonic lethality in homozygous mice. Mol Cell Biol 23:916–922

    CAS  PubMed Central  PubMed  Google Scholar 

  • Olahova M, Taylor SR, Khazaipoul S, Wang JL, Morgan BA, Matsumoto K, Blackwell TK, Veal EA (2008) A redox-sensitive peroxiredoxin that is important for longevity has tissue- and stress-specific roles in stress resistance. Proc Natl Acad Sci USA 105:19839–19844

    CAS  PubMed  Google Scholar 

  • Orr WC, Sohal RS (1994) Extension of life-span by overexpression of superoxide-dismutase and catalase in Drosophila-melanogaster. Science 263:1128–1130

    CAS  PubMed  Google Scholar 

  • Orr WC, Sohal RS (2003) Does overexpression of Cu, Zn-SOD extend life span in Drosophila melanogaster? Exp Gerontol 38:227–230

    CAS  PubMed  Google Scholar 

  • Orrenius S, Moldeus P (1984) The multiple roles of glutathione in drug-metabolism. Trends Pharmacol Sci 5:432–435

    CAS  Google Scholar 

  • Parihar MS, Kunz EA, Brewer GJ (2008) Age-related decreases in NAD(P)H and glutathione cause redox declines before ATP loss during glutamate treatment of hippocampal neurons. J Neurosci Res 86:2339–2352

    CAS  PubMed  Google Scholar 

  • Parkes TL, Elia AJ, Dickinson D, Hilliker AJ, Phillips JP, Boulianne GL (1998) Extension of Drosophila lifespan by overexpression of human SOD1 in motorneurons. Nat Genet 19:171–174

    CAS  PubMed  Google Scholar 

  • Pearl R (1921) The biology of death. Utica, N.Y.: Science Press

    Google Scholar 

  • 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 (2008) Thioredoxin 2 haploinsufficiency in mice results in impaired mitochondrial function and increased oxidative stress. Free Radic Biol Med 44:882–892

    CAS  PubMed  Google Scholar 

  • Perez VI, Bokov A, van Remmen H, Mele J, Ran QT, Ikeno Y, Richardson A (2009a) Is the oxidative stress theory of aging dead? Biochim Biophys Acta Gen Subj 1790:1005–1014

    CAS  Google Scholar 

  • Perez VI, van Remmen H, Bokov A, Epstein CJ, Vijg J, Richardson A (2009b) The overexpression of major antioxidant enzymes does not extend the lifespan of mice. Aging Cell 8:73–75

    CAS  PubMed Central  PubMed  Google Scholar 

  • Perez VI, Cortez LA, Lew CM, Rodriguez M, Webb CR, van Remmen H, Chaudhuri A, Qi WB, Lee S, Bokov A, Fok W, Jones D, Richardson A, Yodoi J, Zhang Y, Tominaga K, Hubbard GB, Ikeno Y (2011) Thioredoxin 1 overexpression extends mainly the earlier part of life span in mice. J Gerontol A Biol Sci Med Sci 66:1286–1299

    PubMed  Google Scholar 

  • Perichon R, Bourre JM (1995) Peroxisomal beta-oxidation activity and catalase activity during development and aging in mouse-liver. Biochimie 77:288–293

    CAS  PubMed  Google Scholar 

  • Petriv OI, Rachubinski RA (2004) Lack of peroxisomal catalase causes a progeric phenotype in Caenorhabditis elegans. J Biol Chem 279:19996–20001

    CAS  PubMed  Google Scholar 

  • Phillips JP, Campbell SD, Michaud D, Charbonneau M, Hilliker AJ (1989) Null mutation of copper-zinc superoxide-dismutase in Drosophila confers hypersensitivity to paraquat and reduced longevity. Proc Natl Acad Sci USA 86:2761–2765

    CAS  PubMed  Google Scholar 

  • Radi R, Turrens JF, Chang LY, Bush KM, Crapo JD, Freeman BA (1991) Detection of catalase in rat heart mitochondria. J Biol Chem 266:22028–22034

    CAS  PubMed  Google Scholar 

  • Radyuk SN, Klichko VI, Orr WC (2004) Profiling Cu, Zn-superoxide dismutase expression in Drosophila melanogaster–a critical regulatory role for intron/exon sequence within the coding domain. Gene 328:37–48

    CAS  PubMed  Google Scholar 

  • Radyuk SN, Michalak K, Klichko VI, Benes J, Rebrin I, Sohal RS, Orr WC (2009) Peroxiredoxin 5 confers protection against oxidative stress and apoptosis and also promotes longevity in Drosophila. Biochem J 419:437–445

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ran QT, Liang HY, Gu MJ, Qi WB, Walter CA, Roberts LJ, Herman B, Richardson A, van Remmen H (2004) Transgenic mice overexpressing glutathione peroxidase 4 are protected against oxidative stress-induced apoptosis. J Biol Chem 279:55137–55146

    CAS  PubMed  Google Scholar 

  • Ran Q, Liang HY, Ikeno Y, Qi WB, Prolla TA, Roberts LJ, Wolf N, Vanremmen H, Richardson A (2007) Reduction in glutathione peroxidase 4 increases life span through increased sensitivity to apoptosis. J Gerontol A Biol Sci Med Sci 62:932–942

    PubMed  Google Scholar 

  • Rando TA, Crowley RS, Carlson EJ, Epstein CJ, Mohapatra PK (1998) Overexpression of copper/zinc superoxide dismutase: a novel cause of murine muscular dystrophy. Ann Neurol 44:381–386

    CAS  PubMed  Google Scholar 

  • Rea S, Johnson TE (2003) A metabolic model for life span determination in Caenorhabditis elegans. Dev Cell 5:197–203

    CAS  PubMed  Google Scholar 

  • Rea SL, Ventura N, Johnson TE (2007) Relationship between mitochondrial electron transport chain dysfunction, development, and life extension in Caenorhabditis elegans. PLOS Biol 5:2312–2329

    CAS  Google Scholar 

  • Rebrin I, Sohal RS (2008) Pro-oxidant shift in glutathione redox state during aging. Adv Drug Deliv Rev 60:1545–1552

    CAS  PubMed Central  PubMed  Google Scholar 

  • Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB (2010) Oxidative stress, inflammation, and cancer how are they linked? Free Radic Biol Med 49:1603–1616

    CAS  PubMed Central  PubMed  Google Scholar 

  • Reveillaud I, Niedzwiecki A, Bensch KG, Fleming JE (1991) Expression of bovine superoxide-dismutase in Drosophila-melanogaster augments resistance to oxidative stress. Mol Cell Biol 11:632–640

    CAS  PubMed Central  PubMed  Google Scholar 

  • Rohrbach S, Gruenler S, Teschner M, Holtz J (2006) The thioredoxin system in aging muscle: key role of mitochondrial thioredoxin reductase in the protective effects of caloric restriction? Am J Physiol Regul Integr Comp Physiol 291:R927–R935

    CAS  PubMed  Google Scholar 

  • Rubner M (1908) Das problem der lebensdauer und seine beziehungen zu ernährung. Oldenbourg, München

    Google Scholar 

  • Salvi M, Battaglia V, Brunati AM, la Rocca N, Tibaldi E, Pietrangeli P, Marcocci L, Mondovi B, Rossi CA, Toninello A (2007) Catalase takes part in rat liver mitochondria oxidative stress defense. J Biol Chem 282:24407–24415

    CAS  PubMed  Google Scholar 

  • Schafer FQ, Buettner GR (2001) Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple. Free Radic Biol Med 30:1191–1212

    CAS  PubMed  Google Scholar 

  • Schlotterer A, Kukudov G, Bozorgmehr F, Hutter H, Du XL, Oikonomou D, Ibrahim Y, Pfisterer F, Rabbani N, Thornalley P, Sayed A, Fleming T, Humpert P, Schwenger V, Zeier M, Hamann A, Stern D, Brownlee M, Bierhaus A, Nawroth P, Morcos M (2009) C-elegans as model for the study of high glucose-mediated life span reduction. Diabetes 58:2450–2456

    CAS  PubMed  Google Scholar 

  • 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 (2005) Extension of murine life span by overexpression of catalase targeted to mitochondria. Science 308:1909–1911

    CAS  PubMed  Google Scholar 

  • Schulz TJ, Zarse K, Voigt A, Urban N, Birringer M, Ristow M (2007) Glucose restriction extends Caenorhabditis elegans life span by inducing mitochondrial respiration and increasing oxidative stress. Cell Metab 6:280–293

    CAS  PubMed  Google Scholar 

  • Sedensky MM, Morgan PG (2006) Mitochondrial respiration and reactive oxygen species in mitochondrial aging mutants. Exp Gerontol 41:237–245

    CAS  PubMed  Google Scholar 

  • Semsei I, Rao G, Richardson A (1991) Expression of superoxide-dismutase and catalase in rat-brain as a function of age. Mech Ageing Dev 58:13–19

    CAS  PubMed  Google Scholar 

  • Senoo-Matsuda N, Yasuda K, Tsuda M, Ohkubo T, Yoshimura S, Nakazawa H, Hartman PS, Ishii N (2001) A defect in the cytochrome b large subunit in complex II causes both superoxide anion overproduction and abnormal energy metabolism in Caenorhabditis elegans. J Biol Chem 276:41553–41558

    CAS  PubMed  Google Scholar 

  • Sentman ML, Granstrom M, Jakobson H, Reaume A, Basu S, Marklund SL (2006) Phenotypes of mice lacking extracellular superoxide dismutase and copper- and zinc-containing superoxide dismutase. J Biol Chem 281:6904–6909

    CAS  PubMed  Google Scholar 

  • Seong KH, Ogashiwa T, Matsuo T, Fuyama Y, Aigaki T (2001) Application of the gene search system to screen for longevity genes in Drosophila. Biogerontology 2:209–217

    CAS  PubMed  Google Scholar 

  • Seto NOL, Hayashi S, Tener GM (1990) Overexpression of Cu-Zn superoxide-dismutase in Drosophila does not affect life-span. Proc Natl Acad Sci USA 87:4270–4274

    CAS  PubMed  Google Scholar 

  • Sohal RS, Arnold L, Orr WC (1990) Effect of age on superoxide-dismutase, catalase, glutathione-reductase, inorganic peroxides, Tba-reactive material, Gsh Gssg, Nadph Nadp+ and Nadh Nad + in Drosophila-melanogaster. Mech Ageing Dev 56:223–235

    CAS  PubMed  Google Scholar 

  • Sohal RS, Ku HH, Agarwal S, Forster MJ, Lal H (1994) Oxidative damage, mitochondrial oxidant generation and antioxidant defenses during aging and in response to food restriction in the mouse. Mech Ageing Dev 74:121–133

    CAS  PubMed  Google Scholar 

  • Sohal RS, Mockett RJ, Orr WC (2002) Mechanisms of aging: an appraisal of the oxidative stress hypothesis. Free Radic Biol Med 33:575–586

    CAS  PubMed  Google Scholar 

  • Someya S, Yu W, Hallows WC, Xu JZ, Vann JM, Leeuwenburgh C, Tanokura M, Denu JM, Prolla TA (2010) Sirt3 mediates reduction of oxidative damage and prevention of age-related hearing loss under caloric restriction. Cell 143:802–812

    CAS  PubMed Central  PubMed  Google Scholar 

  • Stadtman ER (1992) Protein oxidation and aging. Science 257:1220–1224

    CAS  PubMed  Google Scholar 

  • Sun JT, Tower J (1999) FLP recombinase-mediated induction of Cu/Zn-superoxide dismutase transgene expression can extend the life span of adult Drosophila melanogaster flies. Mol Cell Biol 19:216–228

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sun JT, Folk D, Bradley TJ, Tower J (2002) Induced overexpression of mitochondrial Mn-superoxide dismutase extends the life span of adult Drosophila melanogaster. Genetics 161:661–672

    CAS  PubMed  Google Scholar 

  • Sun JT, Molitor J, Tower J (2004) Effects of simultaneous over-expression of Cu/ZnSOD and MnSOD on Drosophila melanogaster life span. Mech Ageing Dev 125:341–349

    CAS  PubMed  Google Scholar 

  • Svensson MJ, Larsson J (2007) Thioredoxin-2 affects lifespan and oxidative stress in Drosophila. Hereditas 144:25–32

    PubMed  Google Scholar 

  • Tatar M, Bartke A, Antebi A (2003) The endocrine regulation of aging by insulin-like signals. Science 299:1346–1351

    CAS  PubMed  Google Scholar 

  • Thornalley PJ, Vasak M (1985) Possible role for metallothionein in protection against radiation-induced oxidative stress. Kinetics and mechanism of its reaction with superoxide and hydroxyl radicals. Biochim Biophys Acta 827:36–44

    CAS  PubMed  Google Scholar 

  • Trachootham D, Lu WQ, Ogasawara MA, Valle NRD, Huang P (2008) Redox regulation of cell survival. Antioxid Redox Signal 10:1343–1374

    CAS  PubMed  Google Scholar 

  • Tsan MF, White JE, Caska B, Epstein CJ, Lee CY (1998) Susceptibility of heterozygous MnSOD gene-knockout mice to oxygen toxicity. Am J Respir Cell Mol Biol 19:114–120

    CAS  PubMed  Google Scholar 

  • Tsuda M, Ootaka R, Ohkura C, Kishita Y, Seong KH, Matsuo T, Aigaki T (2010) Loss of Trx-2 enhances oxidative stress-dependent phenotypes in Drosophila. FEBS Lett 584:3398–3401

    CAS  PubMed  Google Scholar 

  • Turrens JF (1997) Superoxide production by the mitochondrial respiratory chain. Biosci Rep 17:3–8

    CAS  PubMed  Google Scholar 

  • Ushio-Fukai M, Nakamura Y (2008) Reactive oxygen species and angiogenesis: NADPH oxidase as target for cancer therapy. Cancer Lett 266:37–52

    CAS  PubMed Central  PubMed  Google Scholar 

  • van Raamsdonk JM, Hekimi S (2009) Deletion of the mitochondrial superoxide dismutase sod-2 extends lifespan in Caenorhabditis elegans. PLOS Genet 5:e1000361

    PubMed Central  PubMed  Google Scholar 

  • van Raamsdonk JM, Hekimi S (2012) Superoxide dismutase is dispensable for normal animal lifespan. Proc Natl Acad Sci 109:5785–5790

    PubMed  Google Scholar 

  • 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 (2003) Life-long reduction in MnSOD activity results in increased DNA damage and higher incidence of cancer but does not accelerate aging. Phys Genomics 16:29–37

    Google Scholar 

  • van Remmen H, Qi WB, Sabia M, Freeman G, Estlack L, Yang H, Guo ZM, Huang TT, Strong R, Lee S, Epstein CJ, Richardson A (2004) Multiple deficiencies in antioxidant enzymes in mice result in a compound increase in sensitivity to oxidative stress. Free Radic Biol Med 36:1625–1634

    PubMed  Google Scholar 

  • Vanfleteren JR (1993) Oxidative stress and aging in Caenorhabditis-elegans. Biochem J 292:605–608

    CAS  PubMed  Google Scholar 

  • Victor VM, Rocha M, Sola E, Banuls C, Garcia-Malpartida K, Hernandez-Mijares A (2009) Oxidative stress, endothelial dysfunction and atherosclerosis. Curr Pharm Des 15:2988–3002

    CAS  PubMed  Google Scholar 

  • Walker DW, Hajek P, Muffat J, Knoepfle D, Cornelison S, Attardi G, Benzer S (2006) Hypersensitivity to oxygen and shortened lifespan in a Drosophila mitochondrial complex II mutant. Proc Natl Acad Sci USA 103:16382–16387

    CAS  PubMed  Google Scholar 

  • Wang XS, Phelan SA, Forsman-Semb K, Taylor EF, Petros C, Brown A, Lerner CP, Paigen B (2003) Mice with targeted mutation of peroxiredoxin 6 develop normally but are susceptible to oxidative stress. J Biol Chem 278:25179–25190

    CAS  PubMed  Google Scholar 

  • Wang DT, Malo D, Hekimi S (2010) Elevated mitochondrial reactive oxygen species generation affects the immune response via hypoxia-inducible factor-1 alpha in long-lived Mclk1(+/-) mouse mutants. J Immunol 184:582–590

    CAS  PubMed  Google Scholar 

  • Weinkove D, Halstead JR, Gems D, Divecha N (2006) Long-term starvation and ageing induce AGE-1/PI 3-kinase-dependent translocation of DAF-16/FOXO to the cytoplasm. BMC Biol 4:e1741–e7007

    Google Scholar 

  • Winterbourn CC, Hampton MB (2008) Thiol chemistry and specificity in redox signaling. Free Radic Biol Med 45:549–561

    CAS  PubMed  Google Scholar 

  • Wolf N, Penn P, Pendergrass W, van Remmen H, Bartke A, Rabinovitch P, Martin GM (2005) Age-related cataract progression in five mouse models for anti-oxidant protection or hormonal influence. Exp Eye Res 81:276–285

    CAS  PubMed  Google Scholar 

  • Wong A, Boutis P, Hekimi S (1995) Mutations in the Clk-1 gene of Caenorhabditis-elegans affect developmental and behavioral timing. Genetics 139:1247–1259

    CAS  PubMed  Google Scholar 

  • Yanase S, Yasuda K, Ishii N (2002) Adaptive responses to oxidative, damage in three mutants of Caenorhabditis elegans (age-1, mev-1 and daf-16) that affect life span. Mech Age Dev 123:1579–1587

    CAS  Google Scholar 

  • Yanase S, Onodera A, Tedesco P, Johnson TE, Ishii N (2009) SOD-1 deletions in Caenorhabditis elegans alter the localization of intracellular reactive oxygen species and show molecular compensation. J Gerontol A Biol Sci Med Sci 64:530–539

    PubMed  Google Scholar 

  • Yang W, Hekimi S (2010) A mitochondrial superoxide signal triggers increased longevity in Caenorhabditis elegans. PLOS Biol 8:e1000556

    PubMed Central  PubMed  Google Scholar 

  • Yant LJ, Ran QT, Rao L, van Remmen H, Shibatani T, Belter JG, Motta L, Richardson A, Prolla TA (2003) The selenoprotein GPX4 is essential for mouse development and protects from radiation and oxidative damage insults. Free Radic Biol Med 34:496–502

    CAS  PubMed  Google Scholar 

  • Yen K, Patel HB, Lublin AL, Mobbs CV (2009) SOD isoforms play no role in lifespan in ad lib or dietary restricted conditions, but mutational inactivation of SOD-1 reduces life extension by cold. Mech Ageing Dev 130:173–178

    CAS  PubMed  Google Scholar 

  • Yu BP, Yang R (1996) Critical evaluation of the free radical theory of aging – a proposal for the oxidative stress hypothesis. Ann N Y Acad Sci 786:1–11

    CAS  PubMed  Google Scholar 

  • Zangar RC, Davydov DR, Verma S (2004) Mechanisms that regulate production of reactive oxygen species by cytochrome P450. Toxicol Appl Pharmacol 199:316–331

    CAS  PubMed  Google Scholar 

  • Zarse K, Schmeisser S, Groth M, Priebe S, Beuster G, Kuhlow D, Guthke R, Platzer M, Kahn CR, Ristow M (2012) Impaired insulin/IGF1 signaling extends life span by promoting mitochondrial L-proline catabolism to induce a transient ROS signal. Cell Metab 15:451–465

    CAS  PubMed  Google Scholar 

  • Zelko IN, Mariani TJ, Folz RJ (2002) Superoxide dismutase multigene family: a comparison of the CuZn-SOD (SOD1), Mn-SOD (SOD2), and EC-SOD (SOD3) gene structures, evolution, and expression. Free Radic Biol Med 33:337–349

    CAS  PubMed  Google Scholar 

  • Zhang YQ, Ikeno Y, Qi WB, Chaudhuri A, Li Y, Bokov A, Thorpe SR, Baynes JW, Epstein C, Richardson A, van Remmen H (2009) Mice deficient in both Mn superoxide dismutase and glutathione peroxidase-1 have increased oxidative damage and a greater incidence of pathology but no reduction in longevity. J Gerontol A Biol Sci Med Sci 64:1212–1220

    PubMed  Google Scholar 

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Knoefler, D., Tienson, H.L., Jakob, U. (2013). Role of Oxidative Stress in Aging. In: Jakob, U., Reichmann, D. (eds) Oxidative Stress and Redox Regulation. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5787-5_14

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