Endogenous oxidative stress: relationship to aging, longevity and caloric restriction

The Free Radical Theory of Aging Matures

1998 • 3,846 citations

Protein Oxidation in Aging, Disease, and Oxidative Stress

1997 • 3,299 citations

Protein Oxidation and Aging

1992 • 2,687 citations

The mitochondrial generation of hydrogen peroxide. General properties and effect of hyperbaric oxygen

1973 • 2,608 citations

The Biologic Clock: The Mitochondria?

1972 • 1,912 citations

Dilated cardiomyopathy and neonatal lethality in mutant mice lacking manganese superoxide dismutase

1995 • 1,761 citations

Normal oxidative damage to mitochondrial and nuclear DNA is extensive.

1988 • 1,709 citations

Generation of superoxide anion by the NADH dehydrogenase of bovine heart mitochondria

1980 • 1,609 citations

Excess brain protein oxidation and enzyme dysfunction in normal aging and in Alzheimer disease.

1991 • 1,290 citations

Motor neurons in Cu/Zn superoxide dismutase-deficient mice develop normally but exhibit enhanced cell death after axonal injury

1996 • 1,261 citations

Age-related changes in oxidized proteins.

1987 • 1,229 citations

Lipid hydroperoxide generation, turnover, and effector action in biological systems

1998 • 1,188 citations

Oxidative damage to DNA during aging: 8-hydroxy-2'-deoxyguanosine in rat organ DNA and urine.

1990 • 1,100 citations

Oxidative Decay of DNA

1997 • 938 citations

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

1994 • 785 citations

Oxidative damage to mitochondrial DNA shows marked age‐dependent increases in human brain

1993 • 759 citations

Reversal of age-related increase in brain protein oxidation, decrease in enzyme activity, and loss in temporal and spatial memory by chronic administration of the spin-trapping compound N-tert-butyl-alpha-phenylnitrone.

1991 • 734 citations

Mitochondrial disease in superoxide dismutase 2 mutant mice

1999 • 581 citations

Mice Deficient in Cellular Glutathione Peroxidase Develop Normally and Show No Increased Sensitivity to Hyperoxia

1997 • 558 citations

Time, cells, and aging

1962 • 553 citations

Oxidative damage to mitochondrial DNA is inversely related to maximum life span in the heart and brain of mammals

2000 • 536 citations

Exercise intensity and longevity in men. The Harvard Alumni Health Study

1995 • 533 citations

Mitochondrial oxygen radical generation and leak: sites of production in states 4 and 3, organ specificity, and relation to aging and longevity.

1999 • 492 citations

Mice lacking extracellular superoxide dismutase are more sensitive to hyperoxia.

1995 • 484 citations

Relationship between mitochondrial superoxide and hydrogen peroxide production and longevity of mammalian species

1993 • 484 citations

Age-dependent increases in oxidative damage to DNA, lipids, and proteins in human skeletal muscle

1999 • 450 citations

Mice with a Homozygous Null Mutation for the Most Abundant Glutathione Peroxidase, Gpx1, Show Increased Susceptibility to the Oxidative Stress-inducing Agents Paraquat and Hydrogen Peroxide

1998 • 445 citations

Oxidative Stress and Aging

2003 • 416 citations

Protein oxidation and proteolysis during aging and oxidative stress

1989 • 396 citations

Superoxide dismutase: correlation with life-span and specific metabolic rate in primate species.

1980 • 385 citations

Mitochondrial Oxidative Stress Plays a Key Role in Aging and Apoptosis

2000 • 382 citations

Caloric restriction decreases mitochondrial free radical generation at complex I and lowers oxidative damage to mitochondrial DNA in the rat heart

2001 • 369 citations

The rate of free radical production as a determinant of the rate of aging: evidence from the comparative approach

1998 • 352 citations

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

1994 • 346 citations

Human Cu/Zn Superoxide Dismutase (SOD1) Overexpression in Mice Causes Mitochondrial Vacuolization, Axonal Degeneration, and Premature Motoneuron Death and Accelerates Motoneuron Disease in Mice Expressing a Familial Amyotrophic Lateral Sclerosis Mutant SOD1

2000 • 343 citations

Mitochondrial glutathione oxidation correlates with age‐associated oxidative damage to mitochondrial DNA

1996 • 305 citations

NADH- and NADPH-dependent formation of superoxide anions by bovine heart submitochondrial particles and NADH–ubiquinone reductase preparation

1979 • 293 citations

Mitochondria, oxidative stress and aging

2000 • 292 citations

Role of mitochondrial DNA mutations in human aging: Implications for the central nervous system and muscle

1998 • 285 citations

Age- and peroxidative stress-related modifications of the cerebral enzymatic activities linked to mitochondria and the glutathione system

1995 • 284 citations

Microarray Profiling of Gene Expression in Aging and Its Alteration by Caloric Restriction in Mice

2001 • 267 citations

Low Mitochondrial Free Radical Production Per Unit O₂Consumption Can Explain the Simultaneous Presence of High Longevity and High Aerobic Metabolic Rate in Birds

1994 • 260 citations

Comparison of mitochondrial pro-oxidant generation and anti-oxidant defenses between rat and pigeon: possible basis of variation in longevity and metabolic potential

1993 • 234 citations

Effect of voluntary exercise on longevity of rats

1985 • 226 citations

Targeted Deletion of the Cytosolic Cu/Zn-Superoxide Dismutase Gene (<i>Sod1</i>) Increases Susceptibility to Noise-Induced Hearing Loss

1999 • 212 citations

Sites and mechanisms responsible for the low rate of free radical production of heart mitochondria in the long-lived pigeon

1997 • 209 citations

Localization at complex I and mechanism of the higher free radical production of brain nonsynaptic mitochondria in the short-lived rat than in the longevous pigeon.

1998 • 204 citations

Association of a protein structure of probable membrane derivation with HeLa cell mitochondrial DNA near its origin of replication.

1977 • 194 citations

The Mammalian Mre11-Rad50-Nbs1 Protein Complex: Integration of Functions in the Cellular DNA–Damage Response

1999 • 186 citations

Mice lacking cytosolic copper/zinc superoxide dismutase display a distinctive motor axonopathy

1999 • 186 citations

Non-linear accumulation of 8-hydroxy-2′-deoxyguanosine, a marker of oxidized DNA damage, during aging

1996 • 184 citations

Relationship between antioxidant defenses and longevity in different mammalian species

1990 • 175 citations

Hydrogen peroxide production by liver mitochondria in different species

1990 • 173 citations

Oxidative stress and aging in the Mongolian gerbil (Meriones unguiculatus)

1995 • 170 citations

H2O2 production of heart mitochondria and aging rate are slower in canaries and parakeets than in mice: sites of free radical generation and mechanisms involved

1998 • 166 citations

Caloric restriction reduces fiber loss and mitochondrial abnormalities in aged rat muscle

1997 • 162 citations

Induction of beta-polymerase mRNA by DNA-damaging agents in Chinese hamster ovary cells.

1989 • 158 citations

Age-related mitochondrial genotypic and phenotypic alterations in human skeletal muscle

2001 • 156 citations

Effect of short-term caloric restriction on H2O2 production and oxidative DNA damage in rat liver mitochondria and location of the free radical source.

2001 • 152 citations

ADP-regulation of mitochondrial free radical production is different with complex I- or complex II-linked substrates: implications for the exercise paradox and brain hypermetabolism.

1997 • 151 citations

Caloric Restriction Attenuates Dityrosine Cross-Linking of Cardiac and Skeletal Muscle Proteins in Aging Mice

1997 • 148 citations

Localization of the site of oxygen radical generation inside the complex I of heart and nonsynaptic brain mammalian mitochondria.

2000 • 148 citations

Measurements of protein carbonyls, ortho- and meta-tyrosine and oxidative phosphorylation complex activity in mitochondria from young and old rats

2001 • 124 citations

Xeroderma pigmentosum group E binding factor recognizes a broad spectrum of DNA damage

1994 • 114 citations

Overexpression of glutathione reductase extends survival in transgenicDrosophila melanogasterunder hyperoxia but not normoxia

1999 • 114 citations

Multi-Organ Characterization of Mitochondrial Genomic Rearrangements in Ad Libitum and Caloric Restricted Mice Show Striking Somatic Mitochondrial DNA Rearrangements with Age

1997 • 113 citations

A decrease of free radical production near critical targets as a cause of maximum longevity in animals

1994 • 107 citations

Mitochondria, aging and longevity – a new perspective

2001 • 102 citations

The Reductive Hotspot Hypothesis: An Update

2000 • 98 citations

Mitochondrial DNA Mutations in Aging, Disease and Cancer

1998 • 91 citations

8-oxo-deoxyguanosine levels in heart and brain mitochondrial and nuclear DNA of two mammals and three birds in relation to their different rates of aging

1999 • 88 citations

Regional distribution of iron, transferrin, ferritin, and oxidatively-modified proteins in young and aged Fischer 344 rat brains

1997 • 86 citations

The rate of mitochondrial mutagenesis is faster in mice than humans

1997 • 85 citations

Mouse models of mitochondrial disease, oxidative stress, and senescence

1999 • 84 citations

Simultaneous induction of SOD, glutathione reductase, GSH, and ascorbate in liver and kidney correlates with survival during aging

1993 • 83 citations

Susceptibility of Heterozygous MnSOD Gene-Knockout Mice to Oxygen Toxicity

1998 • 79 citations

Age-related changes in oxidative damage to lipids and DNA in rat skin

2001 • 76 citations

Mitochondrial DNA mutations associated with aging and degenerative diseases

1995 • 76 citations

The flux of free radical attack through mitochondrial DNA is related to aging rate

2000 • 75 citations

Age-related Increases in Plasma Phosphatidylcholine Hydroperoxide Concentrations in Control Subjects and Patients with Hyperlipidemia

2000 • 74 citations

Proteolysis, caloric restriction and aging

2001 • 74 citations

Mitochondrial DNA 4977 bp deletion and OH ⁸ dG levels correlate in the brain of aged subjects but not Alzheimer's disease patients

1999 • 74 citations

8-Hydroxyguanine Levels in Nuclear DNA and Its Repair Activity in Rat Organs Associated With Age

1996 • 72 citations

Effect of thyroid hormones on mitochondrial oxygen free radical production and DNA oxidative damage in the rat heart

2000 • 68 citations

Changes in the levels of enzymes which modulate the antioxidant balance occur during aging and correlate with cellular damage

1995 • 59 citations

Changes of 8-hydroxydeoxyguanosine levels in rat organ DNA during the aging process.

1992 • 58 citations

Aging Increases N epsilon -(Carboxymethyl)lysine and Caloric Restriction Decreases N epsilon -(Carboxyethyl)lysine and N epsilon -(Malondialdehyde)lysine in Rat Heart Mitochondrial Proteins

2002 • 56 citations

Age-related change of phosphatidylcholine hydroperoxide and phosphatidylethanolamine hydroperoxide levels in normal human red blood cells

1996 • 47 citations

8OHdG levels in brain do not indicate oxidative DNA damage in Alzheimer's disease

1996 • 45 citations

Relationship between antioxidants, lipid peroxidation and aging

1992 • 44 citations

Life span in birds and the ageing theory of absolute metabolic scope

1993 • 40 citations

Mitochondrial genome mutation in cell death and aging.

1999 • 37 citations

Tissue‐specific Distribution of Multiple Mitochondrial DNA Rearrangements during Human Aging^a

1998 • 34 citations

Effect of aging on mitochondrial and nuclear DNA oxidative damage in the heart and brain throughout the life-span of the rat

2001 • 33 citations

Energy expenditure of rats subjected to long-term food restriction

2001 • 29 citations

Presence of a DNA-4236 bp deletion and 8-hydroxy-deoxyguanosine in mouse cardiac mitochondrial DNA during aging

1996 • 27 citations

Age-associated changes of oxidative modification and turnover of proteins

1995 • 23 citations

Energy expenditure of rats subjected to long-term food restriction

2001 • 19 citations

Mitochondrial DNA Mutations in Aging

1998 • 12 citations

Oxidative Stress as a Governing Factor in Physiological Aging

2000 • 8 citations