The aging process.

Harman, Denham

doi:10.1073/pnas.78.11.7124

Cited by 1,575 publications

(743 citation statements)

References 62 publications

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“…Accumulation of oxidative damage to DNA, proteins and lipids is thought to contribute to the observed decline (1). The increase in cellular damage caused by reactive oxygen species (ROS) with advancing age is supported by several studies (2)(3)(4).…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial oxidant generation and oxidative damage in Ames dwarf and GH transgenic mice

Brown‐Borg

Johnson

Rakoczy

et al. 2001

AGE

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Aging is associated with an accumulation of oxidative damage to proteins, lipids and DNA. Cellular mechanisms designed to prevent oxidative damage decline with aging and in diseases associated with aging. A long-lived mouse, the Ames dwarf, exhibits growth hormone deficiency and heightened antioxidative defenses. In contrast, animals that over express GH have suppressed antioxidative capacity and live half as long as wild type mice. In this study, we examined the generation of H202 from liver mitochondria of Ames dwarf and wild type mice and determined the level of oxidative damage to proteins, lipids and DNA in various tissues of these animals. Dwarf liver mitochondria (24 months) produced less H202 than normal liver in the presence of succinate (p<0.03) andADP (p<0.003). Levels of oxidative DNA damage (8OHdG) were variable and dependent on tissue and age in dwarf and normal mice. Forty-seven percent fewer protein carbonyls were detected in 24-month old dwarf liver tissue compared to controls (p<0.04). Forty percent more (p<0.04) protein carbonyls were detected in liver tissue (3-month old) of GH transgenic mice compared to wild types while 12 month old brain tissue had 53% more protein carbonyls compared to controls (p<0.005). Levels of liver malonaldehyde (lipid peroxidation) were not different at 3 and 12 months of age but were greater in Ames dwarf mice at 24 months compared to normal mice. Previous studies indicate a strong negative correla-

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Section: Introductionmentioning

confidence: 99%

Mitochondrial oxidant generation and oxidative damage in Ames dwarf and GH transgenic mice

Brown‐Borg

Johnson

Rakoczy

et al. 2001

AGE

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“…For these reasons, ROS and the resulting DNA oxidation represent a potentially important source of mutations and one of the causative factors of carcinogenesis, neurodegeneration, and aging [1][2][3]. 8-OH-Gua (also known as 7,8-dihydro-8-oxoguanine) is one of the major oxidized bases [4,5].…”

Section: Introductionmentioning

confidence: 99%

Mutagenic effects of 8-hydroxy-dGTP in live mammalian cells

Satou

Kawai

Kasai

et al. 2007

Free Radical Biology and Medicine

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The mutagenicity of an oxidized form of dGTP, 8-hydroxy-2'-deoxyguanosine 5'-triphosphate (8-OH-dGTP), was examined using COS-7 cells. 8-OH-dGTP and supF shuttle plasmid DNA were co-introduced by means of cationic liposomes, and the DNAs replicated in the cells were recovered and then transfected into Escherichia coli. These results constitute the first direct evidence to show that 8-OH-dGTP actually induces mutations in living mammalian cells. 8-OH-dGTP induced

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“…The nature of the ageing process has been the subject of considerable speculation, but because of its complexity it is still poorly understood (Harman, 1981). One of the most favored theories, the free-radical theory of ageing, proposes that there is a single basic cause of ageing that is modified by genetic and environmental factors (Harman, 1956).…”

Section: Introductionmentioning

confidence: 99%

“…According to this theory, ageing-associated loss of functional capacity is a direct result of the deleterious effects of free radical reactions (Harman, 1956). Indeed, a substantial body of evidence demonstrates that free radical reactions contribute to the degradation of biological systems (Harman, 1981;Martin et al, 1996;Sohal and Weindruch, 1996;Stadtman, 1992).…”

Section: Introductionmentioning

confidence: 99%

Oxidative stress tolerance and longevity in Arabidopsis: the late‐flowering mutant gigantea is tolerant to paraquat

et al. 1998

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SummaryRecent genetic analyses of longevity in animals have revealed that long-lived strains are more tolerant to environmental stresses. To investigate whether extended longevity in Arabidopsis also correlates with an increase in stress tolerance, the response was tested of 11 lateflowering mutants to the superoxide radical-generating herbicide paraquat. A tight correlation between flowering time and paraquat tolerance was found when plants were exposed to low doses of herbicide. Furthermore, the mutant gigantea (gi-3) with the longest delay in flowering time had a high tolerance level to paraquat-induced oxidative stress. All the tested gi alleles had an increased tolerance to paraquat toxicity compared to wild-type, although the actual levels of tolerance differed. In addition, the gi-3 mutant was more tolerant to hydrogen peroxide. These results suggest that the link between longevity and oxidative stress resistance in plants is similar to that found in animals, implying that this phenomenon may be general for all aerobic organisms.

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The aging process.

Cited by 1,575 publications

References 62 publications

Mitochondrial oxidant generation and oxidative damage in Ames dwarf and GH transgenic mice

Mitochondrial oxidant generation and oxidative damage in Ames dwarf and GH transgenic mice

Mutagenic effects of 8-hydroxy-dGTP in live mammalian cells

Oxidative stress tolerance and longevity in Arabidopsis: the late‐flowering mutant gigantea is tolerant to paraquat

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