Prolongation of Life: Role of Free Radical Reactions in Aging

Harman, Denham

doi:10.1111/j.1532-5415.1969.tb02286.x

Cited by 132 publications

(36 citation statements)

References 58 publications

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“…The mechanism by which diabetes results in increased levels oflipid peroxides in serum lipoproteins is unknown. Leading hypotheses that could account for the increased oxidation of lipoproteins include (a) diabetes stimulates peroxide-producing systems such as lipoxygenase ( 16), (b) in diabetes there is a decrease in the antioxidant content of certain tissues, resulting in a decreased protection against oxidation (17)(18)(19), (c) secondary to diabetes there is an increase in tissue damage, resulting in increased oxidation (20,21 ), and (d) in diabetes modification of lipoproteins by glucose enhances the oxidation of lipoproteins (22). Another glycosuria at all times were eliminated from the study.…”

Section: Introductionmentioning

confidence: 99%

The effect of oxidized lipids in the diet on serum lipoprotein peroxides in control and diabetic rats.

Staprãns¹,

Rapp²,

Pan³

et al. 1993

J. Clin. Invest.

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The levels of oxidized serum lipoproteins are increased in humans and animals with diabetes. We have examined the contribution of dietary oxidized lipids on the levels of oxidized lipoproteins. In both control and streptozocin induced diabetic rats, the oxidized lipid content of mesenteric lymph chylomicrons (CM) increased when increasing quantities of oxidized lipids were administered intragastrically. However, at all levels of administered oxidized lipids, the quantity of oxidized lipids in CM was greater in the diabetic animals. These results indicate that oxidized lipids are absorbed and packaged into CM and suggest that there is increased absorption of oxidized lipids in diabetic animals. In nondiabetic rats fed a fat-free diet, the levels of oxidized lipids in their serum lipoproteins were very low. When oxidized lipids were added to the diet, the quantity of peroxides in serum lipoproteins increased about fivefold. In diabetic animals fed a fat-free diet, there were also very low levels of oxidized lipids in their serum lipoproteins, and there was no difference between control and diabetic rats. However, when diabetic animals were fed a diet containing oxidized lipids, the quantity of oxidized lipids in their serum lipoproteins increased 16-fold and were significantly greater than in controls. Thus, in both control and diabetic rats the quantity of oxidized lipids in the diet largely determines the levels of oxidized lipids in circulating lipoproteins. However, in diabetic animals the effect of diet is more pronounced. Together with the CM studies, these results demonstrate that dietary oxidized lipids make a major contribution to the levels of oxidized lipids in circulating lipoproteins and indicate that increased absorption of oxidized lipids in diabetic animals may play a role in the elevation of oxidized lipoproteins observed in this disorder. (J.

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Section: Introductionmentioning

confidence: 99%

The effect of oxidized lipids in the diet on serum lipoprotein peroxides in control and diabetic rats.

Staprãns¹,

Rapp²,

Pan³

et al. 1993

J. Clin. Invest.

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“…The free radical theory of aging assumes that there is a single basic cause of aging, modified by genetic and environmental factors, and postulates that free radical reactions are involved in aging and agerelated disorders [4,5].…”

Section: Introductionmentioning

confidence: 99%

Correlation between NADPH Oxidase and Protein Kinase C in the ROS Production by Human Granulocytes Related to Age

et al. 2002

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Background: Aging may be defined as gradual and progressive changes in an organism that increase the probability of death. Accumulating evidence now indicates that the sum of deleterious free radical reactions going on continuously throughout cells and tissues constitutes the aging process or is a major contributor to it. Objective: The aim of this paper was to study the correlation between NADPH oxidase and protein kinase C (PKC) in the reactive oxygen species (ROS) production related to age. Methods: The age-induced ROS generation was studied in healthy subjects ranging in age from 20 to 80 years, divided into six age groups: (1) 20–29, (2) 30–39, (3) 40–49, (4) 50–59, (5) 60–69, and (6) 70–80 years. The ROS were quantified using a chemiluminescence assay (luminol dependent) and the results expressed as RLU/s at maximum peak and total chemiluminescence (integral under the curve RLU/s). Results: Our results demonstrate a significant increase of the ROS production from 40 years of age (age groups 3–6). In the age groups 1 and 2, we did not observe a significant difference (p > 0.05). These data suggest an increase of the ROS production from 40 to 49 years of age which may be induced by the PKC activity. The selective PKC inhibitor (calphostin C) abrogated the stimulatory effect of phorbol-12,13-dibutyrate on the ROS production. However, the NADPH oxidase inhibitor diphenylene iodonium did not inhibit the total ROS production by granulocytes in relation to age. Conclusions: These data suggest a correlation between age-related PKC activity, NADPH oxidase phosphorylation, and ROS production. The above correlations between unspecific and inflammatory responses related to age are discussed.

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“…This damage is thought to be a basic mechanism underlying many diverse disorders such as atherosclerosis, cancer, aging, rheumatic diseases, cardiac and cerebral ischemia, various liver problems and toxicity induced by harmful environmental factors. It has been considered that the lipid peroxidation damage is involved in aging and pathological disorders [4,5]. Reactive Oxygen Species (ROS) are constantly generated in living cells as a part of intracellular metabolic processes and induce oxidative damage to cell membranes, lipids, proteins and nucleic acids [6,7].…”

Section: Introductionmentioning

confidence: 99%

Effect of Bacoside a on Lipid Peroxidation in D-Galactose Induced Aging Mice

Jadhav

2017

Int J Pharm Pharm Sci

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Objective: Bacoside A is a major bioactive constituent of Bacopa monnieri L having antioxidant property. The objective of this study was to evaluate the effect of Bacoside A, on lipid peroxidation in brain, heart and liver during induced aging. Methods:Male Swiss albino mice, Mus musculus was used for the present investigation. Four experimental groups were used as Group I-Normal adult, Group II-D-galactose induced, Group III-D-galactose induced plus Bacoside A treated and Group IV-Natural aging. The effect of Bacoside A was studied against lipid peroxidation during induced aging. The level of lipid peroxidation in the form of MDA formation was determined and measured in brain, heart and liver. Results:The statistical data obtained were analyzed using one way ANOVA, control vs other groups and results were expressed as mean±SE. In Bacoside A treated group the lipid peroxidation level in heart, brain and liver was significantly decreased (p<0.001) compared to control group. A significant increase (p<0.0001) in the level of lipid peroxidation was observed in D-galactose induced mice. In natural aging group highly significant increase (p<0.0001) in initial lipid peroxidation, ascorbate dependent lipid peroxidation and spontaneous lipid peroxidation was observed. Conclusion:The observations revealed that, lipid peroxidation was reversed in Bacoside A treated group which may be due to antioxidant property of Bacoside A. Thus Bacoside A is able to ameliorate the stress induced changes in lipid peroxidation during aging. The findings also provide a theoretical basis for the development of novel therapeutic formulations, such as antioxidant supplementation to boost antioxidant defenses in the body.

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Prolongation of Life: Role of Free Radical Reactions in Aging

Cited by 132 publications

References 58 publications

The effect of oxidized lipids in the diet on serum lipoprotein peroxides in control and diabetic rats.

The effect of oxidized lipids in the diet on serum lipoprotein peroxides in control and diabetic rats.

Correlation between NADPH Oxidase and Protein Kinase C in the ROS Production by Human Granulocytes Related to Age

Effect of Bacoside a on Lipid Peroxidation in D-Galactose Induced Aging Mice

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