Original ArticlesExtending Functional Life Span
Section snippets
In Appreciation
I am privileged to have an opportunity to contribute a chapter to this book in honor of Alex Comfort. I first met Alex during a symposium on experimental gerontology organized by Professor F. Bourliere, April 2–4, 1962, in Paris. Summaries of the lectures have been published (Bourliere 1962); Alex reported on the effect of restricted feeding on growth and longevity on fish.
Alex is a man of many interests—a true renaissance man. His contributions to biomedical gerontology have added
Free Radical Theory of Aging
Many theories have been advanced to account for aging (Rockstein et al 1974; Warner et al 1987; Medvedev 1990). No one theory is generally accepted (Schneider 1987; Viig 1990). The free radical theory of aging arose in 1954 (Harman 1986, Harman 1992, Harman 1993) from a consideration of aging phenomena from the premise that a single common process, modifiable by genetic and environmental factors, was responsible for the aging and death of all living things, in 1972 the theory was expanded (
Free Radical Reactions
Free radical reactions can be divided into three stages (Pryor 1966; Nonhebel 1974): 1) initiation, 2) propagation, and 3) termination—as illustrated by the reaction of O2 with organic compounds (Fig. 2). The amount converted to products per unit time of a compound involved in a free radical reaction depends on the: 1) rate of initiation and 2) the number of times the propagation phase (see Fig. 2) is repeated before termination, i.e., the chain length. The propagation phase can be shortened
Minimizing Free Radical Reaction Damage
Many studies now attest to the beneficial effects on life span and disease of measures designed to minimize endogenous free radical reactions in the body (Harman 1986, Harman 1993, Harman 1994). Three experiments illustrating the effects of decreased initiation rates are presented below followed by a discussion of the use of antioxidants such as vitamin E to limit free radical damage.
Comment
The participation of free radical reactions in normal metabolism and in the pathogenesis of many diseases is now generally accepted. Whether or not these reactions are responsible for aging is still being debated (Mehlhorn 1985; Rothstein 1986; Schneider 1987; Weindruch et al 1993; Sohal 1993).
Criticism of a theory is helpful, and as a consequence, it is either destroyed, modified, or confirmed; in either case it contributes to the solution of the problem for which the theory was formulated—in
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2018, Journal of Steroid Biochemistry and Molecular BiologyCitation Excerpt :Common to these disease processes is an excess level of reactive oxygen species (ROS) such as superoxide (O2−) and hydrogen peroxide (H2O2) over antioxidants, also known as ‘oxidative stress' [3,4]. Interestingly, the aging process itself involves similar pathophysiological changes as does cardiovascular disease [2], and is the most important nonmodifiable risk factor for death after age 28 [5]. Already 60 years ago, ROS-induced accumulating cell damage has been considered the reason that organisms age [6].
Cancer and Aging: General Principles, Biology, and Geriatric Assessment.
2016, Clinics in Geriatric MedicineCitation Excerpt :In this theory, mutations that are not affected by natural selection early in life tend to accumulate and ultimately result in aging.16 Building on this concept, Denham Harman17 proposed the free radical theory initially in 1954. Through various oxidative stress reactions occurring within organisms, free radicals are generated that lead to damaging effects in DNA and proteins, thereby contributing to aging and potential carcinogenesis.
Biomarkers of Aging and Radiation Therapy Tailored to the Elderly: Future of the Field
2012, Seminars in Radiation OncologyCitation Excerpt :A recurring theme that has emerged in the understanding of the biology of aging is the central role of oxidative damage in the cellular aging process.4 In 1954, the free radical theory was first introduced by Harman et al,8 who hypothesized that free radicals generated through cellular oxidative reactions result in damage to nucleic acids, proteins, and lipids. Over time, the effects of such oxidative damage cause the accumulation of cellular damage that contributes significantly to the aging process.
Evolutionary Optimality of Body Features. Species-Specific Lifespan as a Product of Evolution
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