Skip to main content

Part of the book series: Subcellular Biochemistry ((SCBI,volume 90))

Abstract

The free radical theory of ageing (FRTA), presented by Denham Harman in 1950s, proposed that aerobic organisms age due to reactive oxygen species (ROS)/free radical induced damage that accumulates in cells over time. Since antioxidants can neutralize free radicals by electron donation, the most logical approach was to use them as supplements in order to prevent ageing. In this chapter, we will discuss the inability of antioxidant supplementation to improve health and longevity.

Although many antioxidants are efficient free radical quenchers in vitro, their in vivo effects are less clear. Recent evidence from human trials implies that antioxidant supplements do not increase lifespan and can even increase the incidence of diseases. Synthetic antioxidants were unable to consistently prevent ROS-induced damage in vivo, possibly as dietary antioxidants may not act only as ROS scavengers. Antioxidants can have dichotomous roles on ROS production. They are easily oxidized and can act as oxidants to induce damage when present in large concentrations. In appropriate amounts, they can modulate cellular metabolism by induction of cell stress responses and/or activate cell damage repair and maintenance systems. Therefore, the antioxidants’ beneficial role may be reversed/prevented by excessive amounts of antioxidant supplements. On the other hand, ROS are also involved in many important physiological processes in humans, such as induction of stress responses, pathogen defence, and systemic signalling. Thus, both “anti-oxidative or reductive stress” (the excess of antioxidants) as well as oxidative stress (the excess of ROS) can be damaging and contribute to the ageing processes.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 229.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 299.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Alam MT, Zelezniak A, Muelleder M, Shliaha P, Schwarz R, Capuano F et al (2016) The metabolic background is a global player in Saccharomyces gene expression epistasis. Nat Microbiol 1:15030

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Allen CL, Bayraktutan U (2009) Oxidative stress and its role in the pathogenesis of ischaemic stroke. Int J Stroke 4:461–470

    Article  CAS  PubMed  Google Scholar 

  • Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group (1994) The effects of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med 330(15):1029–1035

    Article  Google Scholar 

  • Ames BN (2001) DNA damage from micronutrient deficiencies is likely to be a major cause of cancer. Mutat Res 475(1–2):7–20

    Article  CAS  PubMed  Google Scholar 

  • Ames BN (2004) Dealying the mitochondrial decay ageing. Ann N Y Acad Sci 1019:406–411

    Article  CAS  PubMed  Google Scholar 

  • Ames BN (2005) Increasing longevity by tuning up metabolism: to maximize human health and lifespan, scientist must abandon outdated models of micronutrients. EMBO Rep 6:S20–S24

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ames BN (2006) Low micronutrient intake may accelerate the degenerative diseases of ageing through allocation of scarce micronutrient by triage. Proc Natl Acad Sci U S A 103(47):17589–17,594

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ames BN, Shigenaga MK, Hagen TM (1993) Oxidants, antioxidants, and the degenerative diseases of ageing. Proc Natl Acad Sci U S A 90(17):7915–7922

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Anisimov VN, Bakeeva LE, Egormin PA et al (2008) Mitochondrial-targeted plastoquinone derivatives as tools to interrupt execution of the ageing program. 5. SkQl prolongs lifespan and prevents development of traits of senescence. Biochemistry 73(12):1329–1342

    CAS  PubMed  Google Scholar 

  • Argüelles S, Gomez A, Machado A, Ayala A (2007) A preliminary analysis of within-subject variation in human serum oxidative stress parameters as a function of time. Rejuvenation Res 10(4):621–636

    Article  PubMed  Google Scholar 

  • Ayyadevara S, Alla R, Thaden JJ, Shmookler Reis RJ (2008) Remarkable longevity and stress resistance of nematode PI3K-null mutants. Ageing Cell 7(1):13–22

    Article  CAS  Google Scholar 

  • Barja G (1998) Mitochondrial free radical production and ageing in mammals and birds. Ann N Y Acad Sci 854:224–238

    Article  CAS  PubMed  Google Scholar 

  • Barja G (2002) Rate of generation of oxidative stress-related damage and animal longevity. Free Radic Biol Med 33(9):1167–1172

    Article  CAS  PubMed  Google Scholar 

  • Barja G (2012) Evolution and longevity. Nova Science Publisher, New York

    Google Scholar 

  • Bases R, Franklin WA, Moy T, Mendez F (1992) Enhanced expression repair activity in mammalian cells after ionizing radiation. Int J Radiat Biol 62(4):427–441

    Article  CAS  PubMed  Google Scholar 

  • Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A et al (2006) Resveratrol improves health and survival of mice on high-caloric diet. Nature 444:337–342

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bautista DM, Movahed P, Hinman A, Axelsson HE, Sterner O, Högestätt ED et al (2005) Pungent products from garlic activate the sensory ion channel TRPA1. Proc Natl Acad Sci U S A 102:12248–12,252

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bedard K, Krause KH (2007) The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev 87(1):245–313

    Article  CAS  PubMed  Google Scholar 

  • Bellavia A, Larsson SC, Bottai M, Wolk A, Orsini N (2013) Fruit and vegetable consumption and all-cause mortality: a dose-response analysis. Am J Clin Nutr 98(2):454–459

    Article  CAS  PubMed  Google Scholar 

  • Bhuiyan MN, Mitsuhashi S, Sigetomi K, Ubukata M (2017) Quercetin inhibits advanced glycation end product formation via chelating metal ions, trapping methylglyoxal, and trapping reactive oxygen species. Biosci Biotechnol Biochem 81(5):882–890

    Article  CAS  PubMed  Google Scholar 

  • Bieganowski P, Brenner C (2004) Discoveries of nicotinamide riboside as a nutrient and conserved NRK genes establish a Preiss-Handler independent route to NAD+ in fungi and humans. Cell 117:495–502

    Article  CAS  PubMed  Google Scholar 

  • Birringer M (2011) Hormetics: dietary triggers of an adaptive stress response. Pharm Res 28(11):2680–2694

    Article  CAS  PubMed  Google Scholar 

  • Bjelakovic G, Nikolova D, Simonetti RG, Gluud C (2004) Antioxidant supplements for prevention of gastrointestinal cancers: a systematic review and meta-analysis. Lancet 364(9441):1219–1228

    Article  CAS  PubMed  Google Scholar 

  • Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C (2007) Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. J Am Med Assoc 297(8):842–857

    Article  CAS  Google Scholar 

  • Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C (2008) Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane Database Syst Rev 2. https://doi.org/10.1002/14651858.CD007176

  • Bogan KL, Brenner C (2008) Nicotinic acid, nicotinamide, and nicotinamide riboside: a molecular evaluation of NAD+ precursor vitamins in human nutrition. Annu Rev Nutr 28:115–130

    Article  CAS  PubMed  Google Scholar 

  • Bokov A, Chaudhuri A, Richardson A (2004) The role of oxidative damage and stress in ageing. Mech Ageing Dev 125(10–11):811–826

    Article  CAS  PubMed  Google Scholar 

  • Bonawitz ND, Rodeheffer MS, Shadel GS (2006) Defective mitochondrial gene expression results in reactive oxygen species-mediated inhibition of respiration and reduction of yeast life span. Mol Cell Biol 26:4818–4829

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bravo L (1998) Polyphenols: chemistry, dietary sources, metabolism, and nutritional significance. Nutr Rev 56:317–333

    Article  CAS  PubMed  Google Scholar 

  • Brunk UT, Jones CB, Sohal RS (1992) A novel hypothesis of lipofuscinogenesis and cellular ageing based on interaction between oxidative stress and autophagocitosis. Mutat Res 275:395–403

    Article  CAS  PubMed  Google Scholar 

  • Bürkle A, Brabeck C, Diefenbach J, Beneke S (2005) The emerging role of poly (ADP-ribose) polymerase-1 in longevity. Int J Biochem Cell Biol 37(5):1043–1053

    Article  CAS  PubMed  Google Scholar 

  • Canto C, Houtkooper RH, Pirinen E, Youn DY, Oosterveer MH, Cen Y et al (2012) The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity. Cell Metab 15(6):838–847

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Caraballoso M, Sacristan M, Serra C, Bonfill X (2003) Drugs for preventing lung cancer in healthy people. Cochrane Database Syst Rev 2:CD002141

    Google Scholar 

  • Cheeseman KH, Slater TF (1993) An introduction to free radical biochemistry. Br Med Bull 49:481–493, Chem Biol Interact 160(1):1–40

    Article  CAS  PubMed  Google Scholar 

  • Cherubini A, Vigna G, Zuliani G, Ruggiero C, Senin U, Fellin R (2005) Role of antioxidants in atherosclerosis: epidemiological and clinical update. Curr Pharm Des 11(16):2017–2032

    Article  CAS  PubMed  Google Scholar 

  • Congdon JD, Nagle RD, Kinney OM, van Loben Sels RC (2001) Hypotheses of ageing in a long-lived vertebrate, Blanding’s turtle (Emydoidea blandingii). Exp Gerontol 36(4–6):813–827

    Article  CAS  PubMed  Google Scholar 

  • Congdon JD, Nagle RD, Kinney OM, van Loben Sels RC, Quinter T, Tinkle DW (2003) Testing hypotheses of ageing in long-lived painted turtles (Chrysemys picta). Exp Gerontol 38(7):765–772

    Article  PubMed  Google Scholar 

  • Deguillaume L, Leriche M, Chaumerliac N (2005) Impact of radical versus non-radical pathway in the Fenton chemistry on the iron redox cycle in clouds. Chemosphere 60:718–724

    Article  CAS  PubMed  Google Scholar 

  • Di Filippo C, Cuzzocrea S, Rossi F, Marfella R, D’Amico M (2006) Oxidative stress as the leading cause of acute myocardial infarction in diabetics. Cardiovasc Drug Rev 24:77–87

    Article  PubMed  Google Scholar 

  • Donato A, Uberoi A, Bailey D, Wray W, Richardson R (2010) Exercise-induced brachial artery vasodilation: effects of antioxidants and exercise training in elderly men. Am J Physiol Heart Circ Physiol 298:H671–H678

    Article  CAS  PubMed  Google Scholar 

  • Doonan R, McElwee JJ, Matthijssens F et al (2008) Against the oxidative damage theory of ageing: superoxide dismutase protect against oxidative stress but have little or no effect on life span in Caenorhabditis elegans. Genes Dev 22(23):3236–3241

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Emanuel P, Scheinfeld N (2007) A review of DNA repair and possible DNA-repair adjuvants and selected natural anti-oxidants. Dermatol Online J 13(3):10

    PubMed  Google Scholar 

  • Federico A, Morgillo F, Tuccillo C, Ciardiello F, Loguercio C (2007) Chronic inflammation and oxidative stress in human carcinogenesis. Int J Cancer 121:2381–2386

    Article  CAS  PubMed  Google Scholar 

  • Fiaschi T, Chiarugi P (2012) Oxidative stress, tumor microenvironment, and metabolic reprogramming: a diabolic liaison. Int J Cell Biol 2012:762825

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Finch CE (1990) Longevity, senescence and the genome. University of Chicago Press, Chicago

    Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Forman HJ, Daves KJ, Ursini F (2014) How do nutritional antioxidants really work: nucleophilic tone para-hormesis versus free radical scavenging in vivo. Free Radic Biol Med 66:24–35

    Article  CAS  PubMed  Google Scholar 

  • Fraga CG, Shigenaga MK, Park JW, Degan P, Ames BN (1990) Oxidative damage to DNA during ageing: 8-hydroxy-2-deoxyguanosine in rat organ DNA and urine. Proc Natl Acad Sci U S A 87:4533–4537

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Frescas D, Valenti L, Accili D (2005) Nuclear trapping of the forkhead transcription factor FoxO1 via Sirt-dependent deacetylation promotes expression of glucogenetic genes. J Biol Chem 280:20589–20,595

    Article  CAS  PubMed  Google Scholar 

  • Fulgencio JP, Kohl C, Girard J, Pegorier JP (2001) Effect of metformin on fatty acid and glucose metabolism in freshly isolated hepatocytes and specific gene expression in cultured hepatocytes. Biochem Pharma 62(4):439–446

    Article  CAS  Google Scholar 

  • Furukawa S, Fujita T, Shimabukuro M, Iwaki M, Yamada Y, Nakajima Y et al (2004) Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest 114:1752–1761

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gems D, Doonan R (2009) Antioxidant defense and ageing in C. elegans: is the oxidative damage theory of ageing wrong? Cell Cycle 8(11):1681–1687

    Article  CAS  PubMed  Google Scholar 

  • Girondot M, Garcia J (1999) Senescence and longevity in turtles: what telomeres tell us. In: Miaud C, Guyetant R (eds) Proceedings of the 9th extraordinary meeting of the Europea Societas Herpetologica. Chambery, France, pp 25–29

    Google Scholar 

  • Gliemann L, Schmidt JF, Olsen J, Biensø RS, Peronard SL, Grandjean SU et al (2013) Resveratrol blunts the positive effects of exercise training on cardiovascular health in aged men. J Physiol 591(20):5047–5059

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gomez Cabrera MC, Domenech E, Romagnoli M, Arduini A, Borras C, Pallardo FV et al (2008) Oral administration of vitamin C decreases muscle mitochondrial biogenesis and hampers training-induced adapations in endurance performance. Am J Clin Nutr 87(1):142–149

    Article  CAS  PubMed  Google Scholar 

  • Goukassian D, Gad F, Yaar M, Eller MS, Nehal US, Gilchrest BA (2000) Mechanisms and implications of the age-associated decrease in DNA repair capacity. FASEB J 14(10):1325–1334

    Article  CAS  PubMed  Google Scholar 

  • Gratão PL, Polle A, Lea PJ, Azevedo RA (2005) Making the life of heavy metal-stressed plants a little easier. Funct Plant Biol 32:481–494

    Article  CAS  PubMed  Google Scholar 

  • Gredilla R, Barja G (2003) Mitochodrial oxidative stress and caloric restriction. Advances in cell ageing and gerontology 14:105–122

    Article  CAS  Google Scholar 

  • Grube K, Bürkle A (1992) Poly (ADP-ribose) polymerase activity in mononuclear leukocytes of 13 mammalian species correlates with species-specific life span. Proc Natl Acad Sci U S A 89(24):11759–11,763

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Halliwel B, Gutteridge JMC (2005) Free radicals in biology and medicine, 4rth edn. Oxford University Press, Oxford

    Google Scholar 

  • Halliwell B (1999) Antioxidant defence mechanisms: from the beginning to the end (of the beginning). Free Radic Res 31(4):261–272

    Article  CAS  PubMed  Google Scholar 

  • Halliwell B (2007) Biochemistry of oxidative stress. Biochem Soc Trans 35(Pt 5):1147–1150

    Google Scholar 

  • Halliwell B (2011) Free radicals and antioxidants – quo vadis? Trends Pharmacol Sci 32(3):125–130

    Article  CAS  PubMed  Google Scholar 

  • Halliwell B, Gutteridge JMC (1984) Oxygen toxicity, oxygen radicals, transition metals and disease. Biochem J 219:1–14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Halliwell B, Gutteridge J (2015) Free radicals in biology and medicine, 5th edn. Clarendon Press, Oxford

    Book  Google Scholar 

  • Hamilton ML, Van Remmen H, Drake JA, Yang H, Guo ZM, Kewitt K et al (2001) Does oxidative damage to DNA increase with age? Proc Natl Acad Sci U S A 98:10469–10474

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hanson RW, Hakimi P (2008) Born to run; the story of the PEPCK-Cmus mouse. Biochimie 90:838–842

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hart RW, Setlow RB (1974) Correlation between deoxyribonucleic acid excision-repair and life-span in a number of mammalian species. Proc Natl Acad Sci U S A 71(6):2169–2173

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • He C, Tsuchiyama SK, Nguyen QT, Plyusnina EN, Terrill SR, Sahibzada S, Patel B, Faulkner AR, Shaposhnikov MV, Tian R, Tsuchiya M, Kaeberlein M, Moskalev AA, Kennedy BK, Polymenis M (2014) Enhanced longevity by ibuprofen, conserved in multiple species, occurs in yeast through inhibition of tryptophan import. PLoS Genet 10(12):e1004860

    Article  PubMed  PubMed Central  Google Scholar 

  • Hipkiss AR (2008) Energy metabolism, altered proteins, sirtuins and ageing: converging mechanisms? Biogerontology 9(1):49–55

    Article  CAS  PubMed  Google Scholar 

  • Houtkooper RH, Canto C, Wanders RJ, Auwerx J (2010) The secret life of NAD+: an old metabolite controlling new metabolic signaling pathways. Endocr Rev 31(2):194–223

    Article  CAS  PubMed  Google Scholar 

  • Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, Wood JG et al (2003) Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 425(6954):191–196

    Article  CAS  PubMed  Google Scholar 

  • Hulbert AJ (2008) Explaining longevity of different animals: is membrane fatty acid composition the missing link? Age 30(2–3):89–97

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hulbert AJ, Pamplona R, Buffenstein R, Buttemer WA (2007) Life and death: metabolic rate, membrane composition, and life span of animals. Physiol Rev 87(4):1175–1213

    Article  CAS  PubMed  Google Scholar 

  • Imai S (2010) The NAD World: a new systemic regulatory network for metabolism and ageing—Sirt1, systemic NAD biosyntesis, and their importance. Cell Biochem Biophys 53(2):65–74

    Article  CAS  Google Scholar 

  • Imlay JA (2003) Pathways of oxidative damage. Annuv Rev Microbiol 57:395–418

    Article  CAS  Google Scholar 

  • Ingram DK, Zhu M, Mamczarz J, Zou S, Lane MA, Roth GS et al (2006) Caloric restriction mimetics: an emerging research field. Ageing Cell 5(2):97–108

    Article  CAS  Google Scholar 

  • Jee J, Lim S, Park J, Kim C (2006) Stabilization of all-trans retinol by loading lipophilic antioxidants in solid lipid nanoparticles. Eur J Pharm Biopharm 63:134–139

    Article  CAS  PubMed  Google Scholar 

  • Jenner P (2003) Oxidative stress in Parkinson’s disease. Ann Neurol 53(3):26–36. https://doi.org/10.1002/ana.10483

    Article  CAS  Google Scholar 

  • Kaiser J (2012) Will an aspirin a day keep the cancer away? Science 337(6101):1471–1473

    Article  CAS  PubMed  Google Scholar 

  • Kand’ar R, Zakova P, Muzakova V (2006) Monitoring of antioxidant properties of uric acid in humans for a consideration measuring of levels of allantoin in plasma by liquid chromatography. Clin Chim Acta 365:249–256

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Khan JA, Forouhar F, Tao X, Tong L (2007) Nicotinamide adenine dinucleotide metabolism as an attractive target for drug discovery. Expert Opin Ther Targets 11:695–705

    Article  CAS  PubMed  Google Scholar 

  • Khlebnikov AI, Schepetkin IA, Domina NG, Kirpotina LN, Quinn MT (2007) Improved quantative structure-activity relationship models to predict antioxidant activity of flavonoids in chemical, enzymatic, and cellular systems. Bioorg Med Chem 15:1749–1770

    Article  CAS  PubMed  Google Scholar 

  • Kim KM, Kim PK, Kwon YG, Bai SK, Nam WD, Kim YM (2002) Regulation of apoptosis by nitrosative stress. J Biochem Mol Biol 35:127–133

    CAS  PubMed  Google Scholar 

  • Kupferschmidt K (2012) Uncertain verdict as vitamin D goes on trial. Science 337(6101):1476–1478

    Article  PubMed  Google Scholar 

  • Lamming DW, Wood JG, Sinclair DA (2004) Small molecules that regulate lifespan: evidence for xenohormesis. Mol Microbiol 53(4):1003–1009

    Article  CAS  PubMed  Google Scholar 

  • Lane MA, Roth GS, Ingram DK (2007) Caloric restriction mimetics: a novel approach for biogerontology. Methods Mol Biol 371:143–149

    Article  CAS  PubMed  Google Scholar 

  • Lanza IR, Short DK, Skort KR, Raghavakaimal S, Basu R, Joyner MJ et al (2008) Endurance exercise as a countermeasure for ageing. Diabetes 57:2933–2942

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee JS, Surh YJ (2005) Nrf2 as a novel molecular target for chemoprevention. Cancer Lett 224:171–184

    Article  CAS  PubMed  Google Scholar 

  • Lewis KN, Andziak B, Yang T, Buffestein R (2013) The naked mole-rat response to oxidative stress: just deal with it. Antioxid Redox Signal 19(12):1388–1399

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Little JB (1976) Relationship between DNA repair capacity and cellular ageing. Gerontology 22(1–2):28–55

    Article  CAS  PubMed  Google Scholar 

  • Liu Y, Long J, Liu J (2014) Mitochondrial free radical theory of ageing: who moved my premise? Geriatr Gerontol Int 14(4):740–749

    Article  PubMed  Google Scholar 

  • Lodish H, Berk A, Matsudaira P, Kaiser CA, Krieger M, Scott MP et al. (2004) Molecular biology of the cell, 5 WH Freeman, New York.

    Google Scholar 

  • Lotito SB, Frei B (2006) Consumption of flavonoid-rich foods and increased plasma antioxidant capacity in humans: cause, consequence, or epiphenomenon. Free Radic Biol Med 41(12):1727–1746

    Article  CAS  PubMed  Google Scholar 

  • Lutz PL, Prentice HM, Milton SL (2003) Is turtle longevity linked to enhanced mechanisms for surviving brain anoxia and reoxygenation? Exp Gerontol 38(7):797–800

    Article  CAS  PubMed  Google Scholar 

  • Markesbery WR (1997) Oxidative stress hypothesis in Alzheimer’s disease. Free Radic Biol Med 23:134–147

    Article  CAS  PubMed  Google Scholar 

  • Mattson MP (2008a) Dietary factors, hormesis and health. Ageing Res Rev 7(1):43–48

    Article  PubMed  Google Scholar 

  • Mattson MP (2008b) Hormesis defined. Ageing Res Rev 7(1):1–7

    Article  CAS  PubMed  Google Scholar 

  • Milisav I, Poljsak B, Suput D (2012) Adaptive response, evidence of cross-resistance and its potential clinical use. Int J Mol Sci 13(9):10771–10,806

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miller ER, Pastor Barriuso R, Dalal D, Riemersma R, Appel LJ, Guallar E (2005a) High-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med 142:37–46

    Article  CAS  PubMed  Google Scholar 

  • Miller ER, Pastor-Barriuso R, Dalal D, Riemersma A, Appel LJ, Guallar E (2005b) Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med 142(1):37–46

    Article  CAS  PubMed  Google Scholar 

  • Mills KF, Yoshida S, Stein LR, Groziol A, Kubota S, Sasaki Y et al (2016) Long-term administration of Nicotinamide Mononucleotide Mitigates age-associated physiological decline in mice. Cell Metab 24:1–12

    Article  CAS  Google Scholar 

  • Mira L, Fernandez MT, Santos M, Rocha R, Florencio MH, Jennings KR (2002) Interactions of flavonoids with iron and copper ions: a mechanism for their antioxidant activity. Free Radic Res 36(11):1199–1208

    Article  CAS  PubMed  Google Scholar 

  • Mockett RJ, Sohal RS, Orr WC (1999) Overexpression of glutathione reductase extends survival in transgenic Drosophila melanogaster under hyperoxia but not normoxia. FASEB J 13(13):1733–1742

    Article  CAS  PubMed  Google Scholar 

  • Morris KC, Lin HW, Thompson JW, Perez Pinzon MA (2011) Pathways for ischemic cytoprotection: role of sirtuins in caloric restriction, resveratrol, and ischemic preconditioning. J Cereb Blood Flow Metab 31(4):1003–1019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Morselli E, Maiuri MC, Markaki M, Megalou E, Pasparaki A, Palikaras K et al (2010) Caloric restriction and resveratrol promote longevity through the Sirtuin-1-dependent induction of autophagy. Cell Death Dis 1(1):e10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Muiras ML, Müller M, Schächter F, Bürkle A (1998) Increased poly (ADP-ribose) polymerase activity in lymphoblastoid cell lines from centenarians. J Mol Med (Berl) 76(5):346–354

    Article  CAS  PubMed  Google Scholar 

  • Mursu J, Robien K, Harnack LJ, Park K, Jacobs DR Jr (2011) Dietary supplements and mortality rate in older women: The iowa women’s health study. Arch Intern Med 171:1625–1633

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nordberg J, Arner ESJ (2001) Reactive oxygen species, antioxidants, and the mammalian thioredoxin system. Free Radic Biol Med 31(11):1287–1312

    Article  CAS  PubMed  Google Scholar 

  • Oliver CN, Ahn BW, Moerman EJ, Goldstein S, Stadtman ER (1987) Age-related changes in oxidized proteins. J Biol Chem 262:5488–5491

    CAS  PubMed  Google Scholar 

  • Orr WC, Sohal RS (1993) Effects of Cu-Zn superoxide dismutase overexpression of life span and resistance to oxidative stress in transgenic Drosophila melanogaster. Arch Biochem Biophys 301(1):34–40

    Article  CAS  PubMed  Google Scholar 

  • Ozbek E (2012) Induction of oxidative stress in kidney. Int J Nephrol 2012:465897

    Article  PubMed  PubMed Central  Google Scholar 

  • Perez VI, Bokov A, Van Remmen H, Mele J, Ran Q, Ikeno Y et al (2009a) Is the oxidative stress theory of ageing dead? Biochimica et Biophysica Acta 1790(10):1005–1014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Perez VI, Buffenstein R, Masamsetti V, Leonard S, Salmon AB, Mele J et al (2009b) Protein stability and resistance to oxidative stress are determinants of longevity in the longest-living rodent, the naked mole-rat. Proc Natl Acad Sci U S A 106(9):3059–3064. https://doi.org/10.1073/pnas.0809620106

    Article  PubMed  PubMed Central  Google Scholar 

  • Perez-Campo R, Lopez-Torres M, Cadenas S, Rojas C, Barja G (1998) The rate of free radical production as a determinant of the rate of ageing: evidence from the comparative approach. J Comp Physiol 168(3):149–158

    Article  CAS  Google Scholar 

  • Piotrowska A, Bartnik E (2014) The role of reactive oxygen species and mitochondria in ageing. Postepy Biochem 60(2):240–247

    CAS  PubMed  Google Scholar 

  • Poljsak B (2011) Strategies for reducing or preventing the generation of oxidative stress. Oxid Med Cell Longev 2011:194586

    CAS  PubMed  PubMed Central  Google Scholar 

  • Poljsak B (2017) NAMPT-mediated nad biosyntesis as the internal timing mechanism: in NAD+ world, time is running in its own way. Rejuvenation Res. https://doi.org/10.1089/rej.2017.1975

  • Poljsak B, Fink R (2014) The protective role of antioxidants in the defence against ROS/RNS-mediated environmental pollution. Oxid Med Cell Longev 2014:671539

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Poljsak B, Milisav I (2012) The neglected significance of “antioxidative stress”. Oxid Med Cell Longev 2012:480895

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Poljsak B, Milisav I (2014) What doesn’t kill us makes us stronger. Nova Science Publisher, New York

    Google Scholar 

  • Poljsak B, Milisav I (2016) NAD+ as the link between oxidative stress, inflammation, caloric restriction, exercise, DNA repair, longevity, and health span. Rejuvenation Res 19(5):406–413

    Article  CAS  PubMed  Google Scholar 

  • Poljsak B, Raspor P (2008) The antioxidant and pro-oxidant activity of vitamin C and trolox in vitro: a comparative study. J Appl Toxicol 28(2):183–188

    Article  CAS  PubMed  Google Scholar 

  • Poljsak B, Gazdag Z, Pesti M, Jenko Brinovec S, Belagy J, Plesničar S et al (2006) Pro-oxidative versus antioxidative reactions between Trolox and Cr(VI): The role of H(2)O(2). Environ Toxicol Pharmacol 22(1):15–19

    Article  CAS  PubMed  Google Scholar 

  • Poljsak B, Milislav I, Lampe T, Ostan I (2011) Reproductive benefit of oxidative damage: an oxidative stress “malevolence”? Oxid Med Cell Longev 2011:760978. https://doi.org/10.1155/2011/760978

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pryor W (1994) Free radicals and lipid peroxidation: what they are and how they got that way. In: Frei B (ed) Natural antioxidants in human health and disease. Academic, San Diego, pp 1–19

    Google Scholar 

  • Rahman K (2007) Studies on free radicals, antioxidants and co-factors. Clin Interv Ageing 2:219–236

    CAS  Google Scholar 

  • Ralser M, Benjamin IJ (2008) Reductive stress on life span extension in C. elegans. BMC Res Notes 1:19

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Raskin I, Ribnicky DM, Komarnytsky S, Ilic N, Poulev A, Borisjuk A et al (2002) Plants and human health in twenty-first century. Trends Biotechnol 20:522–531

    Article  CAS  PubMed  Google Scholar 

  • Reddy L, Odhav B, Bhoola KD (2003) Natural products for cancer prevention: a global perspective. Pharmacol Ther 99:1–13

    Article  CAS  PubMed  Google Scholar 

  • Rhee SG (1999) Redox signaling: hydrogen peroxide as intracellular messenger. Exp Mol Med 31(2):53–59

    Article  CAS  PubMed  Google Scholar 

  • Richardson R, Donato A, Uberoi A, Wray W, Lawrenson L, Nishiyama S, Bailey D (2007) Exercise-induced brachial artery vasodilation: role of free radicals. Am J Physiol Heart Circ Physiol 292(3):H1516–H1522

    Article  CAS  PubMed  Google Scholar 

  • Richter C, Park JW, Ames BN (1988) Normal oxidative damage to mitochondrial and nuclear DNA is extensive. Proc Natl Acad Sci U S A 85(17):6465–6467

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Riley PA (1994) Free radicals in biology: oxidative stress and the effects of ionizing radiation. Int J Radiat Biol 65:27–33

    Article  CAS  PubMed  Google Scholar 

  • Ristow M, Schmeisser S (2011) Extending life span by increasing oxidative stress. Free Radic Biol Med 51(2):327–336

    Article  CAS  PubMed  Google Scholar 

  • Ristow M, Zarse K, Oberbach A, Kloeting N, Birringer M, Kiehntopf M et al (2009) Antioxidants prevent health-promoting effects of physical exercise in humans. Proc Natl Acad Sci U S A 106(21):8665–8670

    Article  PubMed  PubMed Central  Google Scholar 

  • Roberts CK, Sindhu KK (2009) Oxidative stress and metabolic syndrome. Life Sci 84:705–712

    Article  CAS  PubMed  Google Scholar 

  • Rocha M, Hernandez Mijares A, Garcia Malpartida K, Bañuls C, Bellod L, Victor VM (2010) Mitochondria-targeted antioxidant peptides. Curr Pharm Des 16(28):3124–3131

    Article  CAS  PubMed  Google Scholar 

  • Salganik RI (2001) The benefits and hazards of antioxidants: controlling apoptosis and other protective mechanisms in cancer patients and the human population. J Am Coll Nutr 20(5):464S–472S

    Article  CAS  PubMed  Google Scholar 

  • Sanz A, Stefanatos RK (2008) The mitochondrial free radical theory of ageing: a critical view. Curr Ageing Sci 1(1):10–21

    Article  CAS  Google Scholar 

  • Sastre J, Pallardo FV, Garcia De La Asuncion J, Vina J (2000) Mitochondria, oxidative stress and ageing. Free Radic Res 32(3):189–198

    Article  CAS  PubMed  Google Scholar 

  • Sauve AA (2008) NAD+ and vitamin B3: from metabolism to therapies. J Pharmacol Exp Ther 324(3):883–893

    Article  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(4):280–293

    Article  CAS  PubMed  Google Scholar 

  • Schulz TJ, Westermann D, Isken F, Voigt A, Laube B, Thierbach R et al (2010) Activation of mitochondrial energy metabolism protects against cardiac failure. Ageing 2:843–853

    CAS  Google Scholar 

  • Seto NO, Hayashi S, Tener GM (1990) Overexpression of Cu-Zn superoxide dismutase in Drosophila does not affect life-span. Proc Natl Acad Sci U S A 87:4270–4274

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sies H (1991) Oxidative stress II: oxidants and antioxidants. Academic, London

    Google Scholar 

  • Sinclair D, Howitz KT (2006) Dietary restriction, hormesis and small molecule mimetics. In: Masoro EJ, Austad SN (eds) Handbook of the biology of ageing, 6th edn. Academic, Amsterdam, pp 63–105

    Google Scholar 

  • Singh U, Jialal I (2006) Oxidative stress in atherosclerosis. Pathophysiology 13:129–142

    Article  CAS  PubMed  Google Scholar 

  • Skulachev MV, Antonenko YN, Anisimov VN et al (2011) Mitochondrial-targeted plastoquinone derivatives. Effect on senescence and acute age-related pathologies. Curr Drug Targets 12(6):800–826

    Article  CAS  PubMed  Google Scholar 

  • Sohal R, Weindruch R (1996) Oxidative stress, caloric restriction, and ageing. Science 273:59–63

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sosa V, Moline T, Somoza R, Paciucci R, Kondoh H, LL ME (2013) Oxidative stress and cancer: an overview. Ageing Res Rev 12:376–390

    Article  CAS  PubMed  Google Scholar 

  • Speakman JR, Selman C (2011) The free-radical damage theory: accumulating evidence against a simple link of oxidative stress to ageing and lifespan. Bioessays 33(4):255–259

    Article  PubMed  Google Scholar 

  • Spindler SR (2012) Review of the literature and suggestions for the design of rodent survival studies for the identification of compounds that increase health and life span. Age 34(1):111–120

    Article  CAS  PubMed  Google Scholar 

  • Spindler SR, Dhahbi JM, Mote PL, Kim HJ, Tshuchiya T (2003) Rapid identification of candidate CR mimetics using microarrays. Biogerontology 4(1):89

    Google Scholar 

  • Spindler SR, Mote PL, Flegal JM, Teter B (2013) Influence on longevity of blueberry, cinnamon, green and black tea, pomegranate, sesame, curcumin, morin, pycnogenol, quercetin, and taxifolin fed iso-calorically to long-lived, F1 hybrid mice. Rejuvenation Res 16(2):143–151

    Article  CAS  PubMed  Google Scholar 

  • Stanner SA, Hughes J, Kelly CNM, Buttriss J (2004) A review of the epidemiological evidence for the “antioxidant hypothesis”. Public Health Nutr 7(3):407–422

    Article  CAS  PubMed  Google Scholar 

  • Strobel NA, Peake JM, Matsumoto A, Marsh SA, Coombes JS, Wadley GD (2011) Antioxidant supplementation reduces skeletal muscle mitochondrial biogenesis. Med Sci Sports Exerc 43(6):1017–1024

    Article  CAS  PubMed  Google Scholar 

  • Tabassum A, Bristow RG, Venkateswaran V (2010) Ingestion of selenium and other antioxidants during prostate cancer radiotherapy: a good thing? Cancer Treat Rev 36:230–234

    Article  CAS  PubMed  Google Scholar 

  • Terman A, Brunk UT (2006) Oxidative stress, accumulation of biological ‘garbage’, and ageing. Antioxid Redox Signal 8:197–204

    Article  CAS  PubMed  Google Scholar 

  • Thierbach R, Schulz TJ, Isken F, Voigt A, Mietzner B, Drewes G et al (2005) Targeted disruption of hepatic fraxatin expression causes impaired mitochondrial function, decreased life span, and tumor growth in mice. Hum Mol Genet 14:3857–3864

    Article  CAS  PubMed  Google Scholar 

  • Tijskens P (2004) Discovering the future: modelling quality matters. Wageningen University, Wageningen

    Google Scholar 

  • Trammel SAJ, Weidemann J, Chadda A, Yorek MS, Holmes A, Coppey LJ et al (2016) Nicotinamide Riboside opposes Type 2 diabetes and neuropathy in mice. Sci Rep 6:26933

    Article  CAS  Google Scholar 

  • Tsutsui H, Kinugawa S, Matsushima S (2011) Oxidative stress and heart failure. Am J Physiol Heart Circ Physiol 301:2181–2190

    Article  CAS  Google Scholar 

  • Turunen M, Olsson J, Dallner G (2004) Metabolism and function of coenzyme Q. Biochim Biophys Acta 1660:171–199

    Article  CAS  PubMed  Google Scholar 

  • Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J (2007) Free radicals and antioxidants in normal physiological functions and human diseases. Int J Biochem Cell Biol 39:44–84

    Article  CAS  PubMed  Google Scholar 

  • Van Remmen H et al (2003) Life-long reduction in MnSOD activity results in increased DNA damage and higher incidence of cancer but does not accelerate ageing. Physiol Genomics 16:29–37

    Article  CAS  PubMed  Google Scholar 

  • Vivekananthan DP, Penn MS, Sapp SK, Hsu A, Topol EJ (2003) Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-analysis of randomised trials. Lancet 361(9374):2017–2023

    Article  CAS  PubMed  Google Scholar 

  • Wallace DC (2005) A mitochondrial paradigm of metabolic and degenerative diseases, ageing, and cancer: a dawn for evolutionary medicine. Annu Rev Genet 39:359–407

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wani G, Milo GE, SM D’A (1998) Enhanced expression of 8-OHdG triphosphatase gene in human breast tumor cells. Cancer Lett 125(1–2):123–130

    Article  CAS  PubMed  Google Scholar 

  • Warburton DE, Nicol CW, Bredin SS (2006) Health benefits of physical activity: the evidence. Can Med Assoc J 174:801–809

    Article  Google Scholar 

  • Williams KJ, Fisher EA (2005) Oxidation, lipoproteins, and atherosclerosis: which is wrong, the antioxidants or the theory? Curr Opin Clin Nutr Metab Care 8(2):139–146

    Article  CAS  PubMed  Google Scholar 

  • Wood JG, Rogina B, Lavu S, Howitz K, Helfand SL, Tatar M et al (2004) Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Nature 430(7000):686–689

    Article  CAS  PubMed  Google Scholar 

  • World Cancer Research Fund (2017) http://www.wcrf.org/. Accessed 4 Oct 2017

  • World Health Organization (2017) http://www.who.int/en/. Accessed 8 Oct 2017

  • Yang YC, Remmen VH (2009) The mitochondrial theory of ageing: insight from transgenic and knockout mouse models. Exp Gerontol 44(4):256–260

    Article  CAS  Google Scholar 

  • Yang W, Li J, Hekimi S (2007) 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(4):2063–2074

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ying W (2007) Therapeutic potential of NAD+ for neurological diseases. Future Neurol 2:129–132

    Article  CAS  Google Scholar 

  • Zarse K, Schulz TJ, Birringer M, Ristow M (2007) Impaired respiration is positively correlated with decreased life span in Caenorhabditis elegans models of Friedreich ataxia. FASEB J 21:1271–1275

    Article  CAS  PubMed  Google Scholar 

  • Zhan J, Liu YJ, Cai LB, Xu FR, Xie T, He QQ (2017) Fruit and vegetable consumption and risk of cardiovascular disease: A meta-analysis of prospective cohort studies. Crit Rev Food Sci Nutr 57(8):1650–1663

    Article  PubMed  Google Scholar 

  • Zhang YQ, Ikeno Y, Qi WB et al (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 64(12):1212–1220

    Article  CAS  Google Scholar 

  • Zhang H, Ryu D, Wu Y, Gariani K, Wang X, Luan P et al (2016a) NAD+ repletion improves mitochondrial and stem cell function and enhances life span in mice. Science 352(6292):1436–1443. https://doi.org/10.1126/science.aaf2693

    Article  CAS  PubMed  Google Scholar 

  • Zhang W, Chen C, Shi H, Yang M, Liu Y, Ji P et al (2016b) Curcumin is a biologically active copper chelator with antitumor activity. Phytomedicine 23(1):1–8

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors acknowledge the financial support from the Slovenian Research Agency (research core funding No. P3-0019 and P3-0171). This work was also partially supported by the H2020-MSCA-ITN:721236 TREATMENT project.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Irina Milisav .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Milisav, I., Ribarič, S., Poljsak, B. (2018). Antioxidant Vitamins and Ageing. In: Harris, J., Korolchuk, V. (eds) Biochemistry and Cell Biology of Ageing: Part I Biomedical Science. Subcellular Biochemistry, vol 90. Springer, Singapore. https://doi.org/10.1007/978-981-13-2835-0_1

Download citation

Publish with us

Policies and ethics