Abstract
Aging is the progressive accumulation of changes over time that increases the probability of disease and death. There is good reason to believe that molecular damage, and the limited ability of cells, tissues, organs, and individuals to repair it or to maintain function despite it, is the principal driving force of the aging process. A major cause for molecular damage, although by far not the only one (see Chapters 11, 12 and 13, this volume), are highly reactive oxygen-derived free radicals, mostly, but not exclusively endogenously generated, as was first proposed in 1956 by Denham Harman in his “free radical theory of aging” [1]. Denham Harman was also the first to suggest in 1972 a prime role for mitochondria as the biological clock in aging, noting that the rate of oxygen consumption should determine the rate of accumulation of mitochondrial damage produced by free radical reactions [2]. These early suggestions have become a strong and vivid conceptual framework for aging research till today. Thus, a recapitulation of the essentials of the oxygen free radical/antioxidant defense network in animal cells seems to be a prudent opening for a book dealing with the molecular mechanisms of aging. Figure 1 summarizes schematically the interplay between oxygen free radical generation, its damaging effects, and cellular antioxidant responses.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Harman D (1956). Aging: a theory based on free radical and radiation chemistry. J Gerontol. 2: 298–300.
Harman D (1972). The biological clock: the mitochondria? JAm Geriatr Soc. 20: 145–7.
Halliwell B, Gutteridge JMC (1999). Free Radicals in Biology and Medicine, 3rd edn. Oxford: Oxford University Press.
Sohal RS, Brunk UT (1992). Mitochondrial production of pro-oxidants and cellular senescence. Mutat Res. 275: 295–304.
Sohal RS, Orr WC (1992). Relationship between antioxidants, prooxidants, and aging process. Ann NYAcad Sci. 663: 74–84.
Ames BN, Shigenaga MK, Hagen TM (1995). Mitochondrial decay in aging. Biochim Biophys Acta 1271: 165–70.
Sohal RS, Sohal BH, Orr WC (1995). Mitochondrial superoxide and hydrogen peroxide generation, protein oxidative damage, and longevity in different species of flies. Free Rad Biol Med. 19: 499–504.
Garland D (1990). Role of site-specific, metal-catalyzed oxidation in lens aging and cataract: a hypothesis. Exp Eye Res. 50: 677–82.
Rikans LE, Cai Y (1993). Diquat-induced oxidative damage in BCNU-pretreated hepatocytes of mature and old rats. Toxicol Appl Pharmacol. 118: 263–70.
Chance B, Sies H, Boveris A (1979). Hydroperoxide metabolism in mammalian organs. Physiol Rev. 59: 527–605.
Folkes LK, Candeias LP, Wardman, P (1995). Kinetics and mechanisms of hypochlorous acid reactions. Arch Biochem Biophys. 323: 120–6.
Giulivi C, Poderoso JJ, Boveris A (1998). Production of nitric oxide by mitochondria. J Biol Chem. 273: 11038–43.
Bates TE, Loesch A, Burnstock G, Clark JB (1995). Immunocytochemical evidence for a mitochondrially located nitric oxide synthase in brain and liver. Biochem Biophys Res Comm. 213: 896–900.
Bates TE, Loesch A, Burnstock G, Clark JB (1996). Mitochondrial nitric oxide synthase: a ubiquitous regulator of oxidative phosphorylation? Biochem Biophys Res Comm. 218: 40–4.
Laporte F, Doussiere J, Vignais PV (1990). Respiratory burst of rabbit peritoneal neutrophils. Transition from an NADPH diaphorase activity to an O2(-)-generating oxidase activity. Eur J Biochem. 194: 301–8.
Klebanoff SJ (1980). Oxygen metabolism and the toxic properties of phagocytes. Ann Int Med. 93: 480–9.
Hurst JK, Barrette WC Jr (1989). Leukocytic oxygen activation and microbicidal oxidative toxins. Crit Rev Biochem Molec Biol. 24: 271–328.
Eiserich JP, Hristova M, Cross CE, et al. (1998). Formation of nitric oxide-derived inflammatory oxidants by myeloperoxidase in neutrophils. Nature 391: 393–7.
Fridovich I (1995). Superoxide radical and superoxide dismutases. Annu Rev Biochem. 1995; 64: 97–112.
Machlin LJ and Bendich A (1987) Free radical tissue damage: protective role of antioxidant nutrients. FASEB J. 1: 441–5.
Machlin LJ, Gabriel E (1980). Interactions of vitamin E with vitamin C, vitamin B12, and zinc. Ann NY Acad Sci. 355: 98–108.
Ames BN (1983). Dietary carcinogens and anticarcinogens. Oxygen radicals and degenerative diseases. Science 221: 1256–64.
Yu MW, Zhang YJ, Blaner WS, Santella RM (1994). Influence of vitamin A, C, and E and beta-carotene on aflatoxin B1 binding to DNA in woodchuck hepatocytes. Cancer 73: 596–604.
Pauling L (1970). Evolution and the need for ascorbic acid. Proc Natl Acad Sci USA 67: 1643–8.
Benzie IF (2000). Evolution of antioxidant defence mechanisms. Eur J Nutr. 39: 53–61.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2003 Springer Science+Business Media Dordrecht
About this chapter
Cite this chapter
Sitte, N., von Zglinicki, T. (2003). Free Radical Production and Antioxidant Defense: A Primer. In: von Zglinicki, T. (eds) Aging at the Molecular Level. Biology of Aging and Its Modulation, vol 1. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-0667-4_1
Download citation
DOI: https://doi.org/10.1007/978-94-017-0667-4_1
Publisher Name: Springer, Dordrecht
Print ISBN: 978-90-481-6482-0
Online ISBN: 978-94-017-0667-4
eBook Packages: Springer Book Archive