At high concentrations, free radicals and radical-derived, nonradical reactive species are hazardous for living organisms and damage all major cellular constituents. At moderate concentrations, how...

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Free Radicals in the Physiological Control of Cell Function

Beckman, Kenneth B., and Bruce N. Ames. The Free Radical Theory of Aging Matures. Physiol. Rev. 78: 547–581, 1998. — The free radical theory of aging, conceived in 1956, has turned 40 and is rapidl...

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The Free Radical Theory of Aging Matures

Protein Oxidation in Aging, Disease, and Oxidative Stress

Under normal physiological conditions, the use of oxygen by cells of aerobic organisms generates potentially deleterious reactive oxygen metabolites. A chronic state of oxidative stress exists in cells because of an imbalance between prooxidants and antioxidants. The amount of oxidative damage increases as an organism ages and is postulated to be a major causal factor of senescence. Support for this hypothesis includes the following observations: (i) Overexpression of antioxidative enzymes retards the age-related accrual of oxidative damage and extends the maximum life-span of transgenic Drosophila melanogaster. (ii) Variations in longevity among different species inversely correlate with the rates of mitochondrial generation of the superoxide anion radical (O2) and hydrogen peroxide. (iii) Restriction of caloric intake lowers steady-state levels of oxidative stress and damage, retards age-associated changes, and extends the maximum life-span in mammals.

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Oxidative Stress, Caloric Restriction, and Aging

Life is the interplay between structure and energy, yet the role of energy deficiency in human disease has been poorly explored by modern medicine. Since the mitochondria use oxidative phosphorylation (OXPHOS) to convert dietary calories into usable energy, generating reactive oxygen species (ROS) as a toxic by-product, I hypothesize that mitochondrial dysfunction plays a central role in a wide range of age-related disorders and various forms of cancer. Because mitochondrial DNA (mtDNA) is present in thousands of copies per cell and encodes essential genes for energy production, I propose that the delayed-onset and progressive course of the agerelated diseases results from the accumulation of somatic mutations in the mtDNAs of post-mitotic tissues. The tissue-specific manifestations of these diseases may result from the varying energetic roles and needs of the different tissues. The variation in the individual and regional predisposition to degenerative diseases and cancer may result from the interaction of modern dietary caloric intake and ancient mitochondrial genetic polymorphisms. Therefore the mitochondria provide a direct link between our environment and our genes and the mtDNA variants that permitted our forbears to energetically adapt to their ancestral homes are influencing our health today.

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A Mitochondrial Paradigm of Metabolic and Degenerative Diseases, Aging, and Cancer: A Dawn for Evolutionary Medicine

Oxidative damage, mitochondrial oxidant generation and antioxidant defenses during aging and in response to food restriction in the mouse

Effect of age and caloric restriction on DNA oxidative damage in different tissues of C57BL/6 mice

Simultaneous Overexpression of Copper- and Zinc-containing Superoxide Dismutase and Catalase Retards Age-related Oxidative Damage and Increases Metabolic Potential in Drosophila melanogaster

The objective of this study was to explore the relationship between oxidative molecular damage and the aging process by determining whether such damage is associated with the rate of aging, using the adult housefly as the experimental organism. Because the somatic tissues in the housefly consist of long-lived postmitotic cells, it provides an excellent model system for studying cumulative age-related cellular alterations. Rate of aging in the housefly was manipulated by varying the rate of metabolism (physical activity). The concentration of 8-hydroxydeoxyguanosine (80HdG) was used as an indicator of DNA oxidation. Exposure of live flies to x-rays and hyperoxia elevated the level of 8OHdG. The level of 8OHdG in mitochondrial as well as total DNA increased with the age of flies. Mitochondrial DNA was 3 times more susceptible to age-related oxidative damage than nuclear DNA. A decrease in the level of physical activity of the flies was found to prolong the life-span and corresponding reduce the level of 8OHdG in both mitochondrial and total DNA. Under all conditions examined, mitochondrial DNA exhibited a higher level of oxidative damage than total DNA. The 8OHdG levels were found to be inversely associated with the life expectancy of houseflies. The pattern of age-associated accrural of 8OHdG was virtually identical to that of protein carbonyl content. Altoghether, results of this study support the hypothesis that oxidative molecular damage is a causal factor in senescence.

https://www.pnas.org/content/pnas/91/25/12332.full.pdf

DNA oxidative damage and life expectancy in houseflies.

Lycopene is a bioactive carotenoid present in many fruits and vegetables. Tomatoes constitute the major dietary source of lycopene. Recent evidence shows lycopene to be associated with several health benefits. However, very little information is available about the stability of lycopene and its bioavailability. Because tomatoes undergo extensive processing and storage before consumption, a study was conducted to evaluate the stability, isomeric form, bioavailability, and in vivo antioxidant properties of lycopene. Total lycopene and isomers were measured by spectrophotometry and high-performance liquid chromatography, respectively. Lycopene content of tomatoes remained unchanged during the multistep processing operations for the production of juice or paste and remained stable for up to 12 months of storage at ambient temperature. Moreover, subjecting tomato juice to cooking temperatures in the presence of corn oil resulted in the formation of the cis isomeric form, which was considered to be more bioavailable. Lycopene was absorbed readily from the dietary sources. Serum lipid and low-density lipoprotein oxidation were significantly reduced after the consumption of tomato products containing lycopene.

Sanjiv Agarwal

Papers

Oxidative damage, mitochondrial oxidant generation and antioxidant defenses during aging and in response to food restriction in the mouse

Effect of age and caloric restriction on DNA oxidative damage in different tissues of C57BL/6 mice

Simultaneous Overexpression of Copper- and Zinc-containing Superoxide Dismutase and Catalase Retards Age-related Oxidative Damage and Increases Metabolic Potential in Drosophila melanogaster

DNA oxidative damage and life expectancy in houseflies.

Lycopene Content of Tomato Products: Its Stability, Bioavailability and In Vivo Antioxidant Properties.