Free Radical Production and Antioxidant Defense: A Primer

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.