The free radical theory of aging: A critical review

[30] Microsomal lipid peroxidation

1978 • 12,818 citations

Superoxide Dismutase

1969 • 12,578 citations

Aging: A Theory Based on Free Radical and Radiation Chemistry

1956 • 8,252 citations

Hydroperoxide metabolism in mammalian organs.

1979 • 5,821 citations

The limited in vitro lifetime of human diploid cell strains

1965 • 5,595 citations

Oxygen toxicity, oxygen radicals, transition metals and disease

1984 • 5,301 citations

Chronic Parkinsonism in Humans Due to a Product of Meperidine-Analog Synthesis

1983 • 4,822 citations

Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters.

1982 • 4,786 citations

The Causes of Cancer: Quantitative Estimates of Avoidable Risks of Cancer in the United States Today

1981 • 3,794 citations

Dietary Carcinogens and Anticarcinogens

1983 • 3,028 citations

Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis.

1981 • 2,777 citations

Carcinogens are Mutagens: A Simple Test System Combining Liver Homogenates for Activation and Bacteria for Detection

1973 • 2,275 citations

The Effect of Retarded Growth Upon the Length of Life Span and Upon the Ultimate Body Size

1935 • 2,189 citations

The Metabolic Basis of Inherited Disease

1979 • 2,083 citations

Modification of low density lipoprotein by endothelial cells involves lipid peroxidation and degradation of low density lipoprotein phospholipids.

1984 • 1,631 citations

The cellular production of hydrogen peroxide

1972 • 1,526 citations

Formation of germ-line chimaeras from embryo-derived teratocarcinoma cell lines

1984 • 1,518 citations

Replicative life-span of cultivated human cells. Effects of donor's age, tissue, and genotype.

1970 • 1,002 citations

The Free Radical Theory of Aging

2003 • 902 citations

Evidence for a Monoclonal Origin of Human Atherosclerotic Plaques

1973 • 900 citations

Hypolipidaemic hepatic peroxisome proliferators form a novel class of chemical carcinogens

1980 • 854 citations

Malondialdehyde alteration of low density lipoproteins leads to cholesteryl ester accumulation in human monocyte-macrophages

1980 • 851 citations

Iron-catalyzed hydroxyl radical formation. Stringent requirement for free iron coordination site.

1984 • 849 citations

Increase of NAD(P)H:quinone reductase by dietary antioxidants: possible role in protection against carcinogenesis and toxicity.

1980 • 757 citations

Superoxide and Superoxide Dismutases

1978 • 754 citations

Parkinson's disease: A disorder due to nigral glutathione deficiency?

1982 • 746 citations

Prostaglandins, Arachidonic Acid, and Inflammation

1980 • 690 citations

Role of ubiquinone in the mitochondrial generation of hydrogen peroxide

1976 • 656 citations

The origin of human cancers

1981 • 653 citations

Spin trapping. Kinetics of the reaction of superoxide and hydroxyl radicals with nitrones

1980 • 635 citations

Superoxide radicals as precursors of mitochondrial hydrogen peroxide

1974 • 627 citations

Separation and characterization of the aldehydic products of lipid peroxidation stimulated by ADP-Fe2+ in rat liver microsomes

1982 • 614 citations

ASSOCIATION BETWEEN CARDIOVASCULAR DEATH AND MYOCARDIAL INFARCTION AND SERUM SELENIUM IN A MATCHED-PAIR LONGITUDINAL STUDY

1982 • 576 citations

Life Span Study of SPF Fischer 344 Male Rats Fed AdLibitum or Restricted Diets: Longevity, Growth, Lean Body Mass and Disease

1982 • 573 citations

The Biology of Senescence

1978 • 539 citations

Do Mitochondria Produce Oxygen Radicals in vivo?

1978 • 530 citations

DT-diaphorase as a quinone reductase: A cellular control device against semiquinone and superoxide radical formation

1982 • 530 citations

Skin Tumor-Promoting Activity of Benzoyl Peroxide, a Widely Used Free Radical-Generating Compound

1981 • 510 citations

AETIOLOGY OF PARKINSON'S DISEASE

1983 • 463 citations

Biochemical adaptation of mitochondria, muscle, and whole-animal respiration to endurance training

1981 • 433 citations

A method for the isolation of longevity mutants in the nematode Caenorhabditis elegans and initial results

1983 • 427 citations

Mitochondrial production of superoxide anions and its relationship to the antimycin insensitive respiration

1975 • 403 citations

Brain Peroxidase and Catalase in Parkinson Disease

1975 • 394 citations

Thymine glycol and thymidine glycol in human and rat urine: a possible assay for oxidative DNA damage.

1984 • 365 citations

The Immunologic Theory of Aging

1971 • 363 citations

Evidence for a relationship between longevity of mammalian species and life spans of normal fibroblasts in vitro and erythrocytes in vivo

1981 • 348 citations

Retarded Growth, Life Span, Ultimate Body Size and Age Changes in the Albino Rat after Feeding Diets Restricted in Calories

1939 • 347 citations

Restoration of dopaminergic function by grafting of fetal rat substantia nigra to the caudate nucleus: Long‐term behavioral, biochemical, and histochemical studies

1980 • 340 citations

Free Radical Theory of Aging: Effect of Free Radical Reaction Inhibitors on the Mortality Rate of Male LAF1 Mice

1968 • 339 citations

The Radicals in Cigarette Tar: Their Nature and Suggested Physiological Implications

1983 • 313 citations

Familial constitutional panmyelocytopathy, Fanconi's anemia (F.A.). I. Clinical aspects.

1967 • 308 citations

Catecholamine toxicity: a proposal for the molecular pathogenesis of manganese neurotoxicity and Parkinson's disease.

1984 • 291 citations

Intraclonal Variation in Proliferative Potential of Human Diploid Fibroblasts: Stochastic Mechanism for Cellular Aging

1980 • 290 citations

Genetic syndromes in man with potential relevance to the pathobiology of aging.

1978 • 290 citations

The production of free radicals during the autoxidation of cysteine and their effect on isolated rat hepatocytes

1982 • 283 citations

Antioxidants, Aging, and Longevity

1984 • 279 citations

Oxygen-dependence of chromosomal aberrations in Fanconi's anaemia

1981 • 275 citations

Free radicals in molecular biology, aging, and disease

1985 • 271 citations

Mutagenicity of oxygen free radicals.

1982 • 270 citations

Comparison of superoxide with other reducing agents in the biological production of hydroxyl radicals

1979 • 268 citations

DNA Strand Breakage in Human Leukocytes Exposed to a Tumor Promoter, Phorbol Myristate Acetate

1982 • 255 citations

ATAXIA TELANGIECTASIA: An Inherited Human Disorder Involving Hypersensitivity to Ionizing Radiation and Related DNA-Damaging Chemicals

1979 • 254 citations

FREE RADICAL BIOLOGY: XENOBIOTICS, CANCER, AND AGING*

1982 • 252 citations

Hydroxyl radical production in body fluids Roles of metal ions, ascorbate and superoxide

1981 • 250 citations

Coupling of Dopamine Oxidation (Monoamine Oxidase Activity) to Glutathione Oxidation Via the Generation of Hydrogen Peroxide in Rat Brain Homogenates

1981 • 247 citations

The Regulation of Physiological Changes During Mammalian Aging

1976 • 245 citations

Action of food restriction in delaying the aging process.

1982 • 243 citations

Is Cell Aging Caused by Respiration-Dependent Injury to the Mitochondrial Genome?

1982 • 242 citations

Free radical theory of aging: Consequences of mitochondrial aging

1983 • 239 citations

Length of Life and Nutrition in the Rat

1961 • 236 citations

Studies on Parkinson's Disease Including X-Ray Fluorescent Spectroscopy of Formalin Fixed Brain Tissue

1968 • 227 citations

Oxidation of glutathione by the superoxide radical to the disulfide and the sulfonate yielding singlet oxygen

1983 • 227 citations

Effect of Antioxidants and Nutrients on Lipid Peroxidation Fluorescent Products and Aging Parameters in the Mouse

1973 • 224 citations

The pathobiology of Parkinson's disease: biochemical aspects of dopamine neuron senescence.

1983 • 224 citations

Oxy-radical toxicity in catecholamine neurons.

1984 • 221 citations

Possible role of neuromelanin in the pathogenesis of Parkinson's disease

1983 • 210 citations

Tumour promoter phorbol-12-myristate-13-acetate induces chromosomal damage via indirect action

1981 • 205 citations

Free Radicals in Molecular Biology, Aging, and Disease

1985 • 203 citations

Effect of dietary vitamin E on dimethylhydrazine-induced colonic tumors in mice.

1980 • 189 citations

Effect of high and low density lipoproteins on proliferation of cultured bovine vascular endothelial cells.

1980 • 185 citations

MEMBRANE EFFECTS OF VITAMIN E DEFICIENCY: BIOENERGETIC AND SURFACE CHARGE DENSITY STUDIES OF SKELETAL MUSCLE AND LIVER MITOCHONDRIA*

1982 • 184 citations

In Vivo Lipid Peroxidation in Rat Brain Following Intracortical Fe²⁺ Injection

1984 • 182 citations

Cytotoxicity of oxidation derivatives of cholesterol on cultured aortic smooth muscle cells and their effect on cholesterol biosynthesis

1979 • 182 citations

Changes in the activity and amounts of enzymes synthesizing catecholamines and acetylcholine in brain, adrenal medulla, and sympathetic ganglia of aged rat and mouse

1977 • 180 citations

The control of muscle and cartilage development in the chick limb: the role of differential vascularization

1973 • 176 citations

The immunologic theory of aging

1970 • 168 citations

Comparison of cytoplasmic superoxide dismutase in liver, heart and brain of aging rats and mice

1976 • 161 citations

Hydroxymethyluracil DNA glycosylase in mammalian cells.

1984 • 157 citations

Hydroxyl radical generation by polymorphonuclear leukocytes measured by electron spin resonance spectroscopy.

1979 • 156 citations

Principles of mammalian aging

1971 • 150 citations

Thiol-dependent lipid peroxidation

1982 • 142 citations

The pathogenesis of atherosclerosis

1979 • 141 citations

Kinetics and mechanisms of catalase in peroxisomes of the mitochondrial fraction

1971 • 138 citations

A method for the detection of superoxide in biological systems

1982 • 138 citations

Protection of phagocytic leukocytes by endogenous glutathione: studies in a family with glutathione reductase deficiency

1979 • 136 citations

Testing the Theories of Aging

1983 • 132 citations

Effect of Ethoxyquin on the Longevity of C3H Mice

1971 • 129 citations

Modification of age-related immune decline in mice dietarily restricted from or after midadulthood.

1982 • 128 citations

Regional Distribution of Catalase in the Adult Rat Brain

1981 • 128 citations

Cell differentation, aging and cancer: The possible roles of superoxide and superoxide dismutases

1980 • 126 citations

Superoxide Dismutase in the Rat and Mouse as a Function of Age and Longevity

1976 • 125 citations

Growth, ageing, chronic diseases, and life span in rats.

1943 • 123 citations

Prolongation of the Normal Lifespan and Inhibition of Spontaneous Cancer by Antioxidants

1961 • 122 citations

Pathological changes of thymic epithelial cells and autoimmune disease in NZB, NZW and (NZB x NZW)F1 mice.

1967 • 121 citations

Oxygen regulation of anaerobic and aerobic genes mediated by a common factor in yeast.

1984 • 119 citations

Optical measurement of the catalase-hydrogen peroxide intermediate (Compound I) in the liver of anaesthetized rats and its implication to hydrogen peroxide production in situ

1975 • 116 citations

The Free-Radical Theory of Aging

1982 • 115 citations

Generation of prostacyclin-like substance and lipid peroxidation in vitamin E-deficient rats

1980 • 115 citations

Clastogenic activity from Bloom syndrome fibroblast cultures.

1981 • 114 citations

Oxygen modulates growth of human cells at physiologic partial pressures.

1984 • 111 citations

Long-Term Culture of Human Adult Liver Cells: Morphological Changes Related to <i>in vitro</i> Senescence and Effect of Donor’s Age on Growth Potential

1973 • 109 citations

Effect of Antioxidants on Life-Span of C57BL Mice

1971 • 109 citations

Lipid Peroxide Distribution in Brain and the Effect of Hyperbaric Oxygen

1983 • 109 citations

Protection of Human Neutrophils by Endogenous Catalase

1980 • 108 citations

The Effect of Dietary Restriction of Varying Duration on Survival, Tumor Patterns, Immune Function, and Body Temperature in B10C3F1 Female Mice

1983 • 107 citations

Effects of thyroxine and low oxygen tension on chondrogenic expression in cell culture

1969 • 106 citations

Differential Changes in Superoxide Dismutase Activity in Brain and Liver of Old Rats and Mice

1983 • 105 citations

Prolongation of the Normal Life Span by Radiation Protection Chemicals

1957 • 105 citations

Regression of Aflatoxin B ₁ -Induced Hepatocellular Carcinomas by Reduced Glutathione

1981 • 103 citations

Diminished in vitro tyrosine kinase activity of the EGF receptor of senescent human fibroblasts

1983 • 102 citations

Effect of dietary 2-mercaptoethanol on the life span, immune system, tumor incidence and lipid peroxidation damage in spleen lymphocytes of aging BC3F1 mice

1984 • 101 citations

Selenium and Tellurium in Rats: Effect on Growth, Survival and Tumors

1971 • 97 citations

Dihydroorotate-dependent superoxide producton in rat brain and liver

1976 • 93 citations

On the role of aging in cancer incidence

1980 • 93 citations

Age-Dependent Changes in Lipid Peroxide Levels in the Lipoprotein Fractions of Human Serum

1984 • 91 citations

Regional Distribution of Glutathione Peroxidase in the Adult Rat Brain

1980 • 89 citations

Mechanism of activation of an N-ras oncogene of SW-1271 human lung carcinoma cells.

1984 • 88 citations

The effect of oxygen and vitamin E on the lifespan of human diploid cells in vitro.

1977 • 86 citations

Neuron numbers in locus coeruleus do not change with age in fisher 344 rat

1981 • 83 citations

Principles of Mammalian Aging

1972 • 83 citations

Microperoxisome distribution in the central nervous system of the rat

1976 • 82 citations

Suppression of tumor promoter phorbolmyristate acetate-induced chromosome breakage by antioxidants and inhibitors of arachidonic acid metabolism

1983 • 82 citations

Theories of Life-History Evolution

1983 • 82 citations

Studies on ageing in nematodes IV. The effect of anti-oxidants on cellular damage and life span

1972 • 81 citations

Responses of mitochondrial superoxide dismutase, catalase and glutathione peroxidase activities to aging

1979 • 81 citations

The Effect of Lowered Body Temperature on Lifespan and Immune and Non-Immune Processes

1972 • 80 citations

Favorable effects of the antioxidants sodium and magnesium thiazolidine carboxylate on the vitality and life span of Drosophila and mice

1979 • 80 citations

Are physiological oxygen concentrations mutagenic?

1978 • 79 citations

Free radical theory of aging: Beneficial effect of antioxidants on the life span of male NZB mice; role of free radical reactions in the deterioration of the immune system with age and in the pathogenesis of systemic lupus erythematosus

1980 • 78 citations

Superoxide Dismutase Activities in Aging Rat Brain

1982 • 78 citations

The Chemopreventive Role of Selenium in Carcinogenesis

1986 • 77 citations

The Cellular Aging of Rat Fibroblasts <i>in vitro </i>Is a Differentiation Process

1979 • 77 citations

Superoxide dismutase activities of blood platelets in trisomy 21

1975 • 75 citations

Free radicals and the action of inhibitors of radical processes under pathological states and ageing in living organisms and in man

1976 • 70 citations

Increased Sensitivity of Lymphocytes from People Over 65 to Cell Cycle Arrest and Chromosomal Damage

1983 • 68 citations

Age-related decrease in prostacyclin biosynthetic activity in rat aortic smooth muscle cells

1980 • 66 citations

Ethnic variation in red cell glutathione peroxidase activity

1975 • 66 citations

Age‐Dependent Variations in Peroxide‐Utilizing Enzymes from Rat Brain Mitochondria and Cytoplasm

1984 • 65 citations

A mechanism for primaquine mediated oxidation of NADPH in red blood cells

1983 • 64 citations

Effects of centrophenoxine on the lipofuscin pigments in the nervous system of old rats

1974 • 63 citations

Lysosomes, membranes and aging

1971 • 63 citations

The role of free oxygen radicals in tumor promotion and carcinogenesis.

1982 • 63 citations

The Effect of Reduced Dietary Intake on Enzymatic Activities and Life Span of Rats

1965 • 60 citations

Do Hyperplastoid Cell Lines “Differentiate Themselves to Death”?

1975 • 59 citations

The physiology of growth

1978 • 59 citations

Correlation between DNA repair of embryonic fibroblasts and different life span of 3 inbred mouse strains.

1978 • 58 citations

‘NEURONAL FALL-OUT’ IN THE AGEING BRAIN: A CRITICAL REVIEW OF THE QUANTITATIVE DATA

1974 • 57 citations

Comparison of doubling numbers attained by cultured animal cells with life span of species

1975 • 57 citations

Hormones in development and aging

1983 • 56 citations

Ageing of Neurospora crassa. I. Evidence for the free radical theory of ageing from studies of a natural-death mutant

1976 • 54 citations

Enhancement of the primary antibody response by 2‐mercaptoethanol is mediated by its action on glutathione in the serum

1980 • 54 citations

Correlation between DNA repair of embryonic fibroblasts and different life span of 3 inbred mouse strains

1978 • 53 citations

[89] Measurements of volumes and electrochemical gradients with spin probes in membrane vesicles

1982 • 53 citations

Characterization of an oxygen-tolerant cell line derived from Chinese hamster ovary

1985 • 52 citations

Isolation of autofluorescent ‘aged’ human fibroblasts by flow sorting

1982 • 52 citations

Genetically determined conidial longevity is positively correlated with superoxide dismutase, catalase, glutathione peroxidase, cytochrome c peroxidase, and ascorbate free radical reductase activities in Neurospora crassa

1984 • 50 citations

Dietary Protein, Life-span, and Physiological Variables in Female Mice

1976 • 49 citations

Role of metabolic rate and DNA-repair in Drosophila aging:

1983 • 49 citations

Defective DNA repair and increased lethality in ataxia telangiectasia cells exposed to 4-nitroquinoline-1-oxide

1980 • 45 citations

Immunological abnormalities of aging: an analysis of T lymphocyte subpopulations of Werner's syndrome.

1979 • 43 citations

Inhibition of benzo(a)pyrene Carcinogenesis in rats with vitamin C

1980 • 42 citations

Restoration of impaired immune functions in aging animals. II. Effect of mercaptoethanol in enhancing the reduced primary antibody responsiveness in vitro

1979 • 42 citations

PROGRESSIVE NEUROMUSCULAR DISEASE IN CHILDREN WITH CHRONIC CHOLESTASIS AND VITAMIN E DEFICIENCY: CLINICAL AND MUSCLE BIOPSY FINDINGS AND TREATMENT WITH α‐TOCOPHEROL*

1982 • 42 citations

Immunoreactive Cu SOD and Mn SOD in the circulating blood cells from normal and trisomy 21 subjects

1981 • 42 citations

[27] High-pressure liquid chromatography-electrochemical detection of oxygen free radicals

1984 • 41 citations

Thymosin-producing Cells of the Thymus

1973 • 41 citations

Age-Related Changes in Enzymes of Rat Brain

1981 • 41 citations

Oxygen radicals and hydrogen peroxide in rat brain mitochondria

1974 • 40 citations

Superoxide Dismutase, Longevity and Specific Metabolic Rate

1983 • 39 citations

Unique increase of superoxide dismutase level in brains of long living mammals

1984 • 37 citations

A quantitative study of lipofuscin accumulation with age in normals and individuals with Down's syndrome, phenylketonuria, progeria and transneuronal atrophy

1979 • 35 citations

Autoimmunity, histocompatibility, and aging

1979 • 35 citations

Inhibition of peroxidation in linoleic acid membranes by nitroxide radicals, butylated hydroxytoluene, and α-tocopherol

1981 • 35 citations

Effects of marrow donor and recipient age on immune responses.

1984 • 33 citations

Tissue Vitamin E Levels and Lipofuscin Accumulation With Age in the Mouse

1981 • 32 citations

Cancer and normal ageing

1984 • 32 citations

The secrets of cancer

1982 • 30 citations

Increased production of mutagenic metabolites of carcinogens by tissues from senescent rodents.

1979 • 28 citations

Activation of cyclic adenosine 3':5'-monophosphate-dependent protein kinase in H35 hepatoma and Chinese hamster ovary cells by a phorbol ester tumor promoter.

1983 • 28 citations

Why Are Babies Young?: Meiosis May Prevent Aging of the Germ Line

1979 • 28 citations

Nitroxide destruction and flavin-photosensitized damage in inner mitochondrial membranes

1982 • 27 citations

Restoration of impaired immune functions in aging animals. III. Effect of mercaptoethanol in enhancing the reduced primary antibody responsiveness in vivo

1979 • 26 citations

Dietary restriction and the aging process

1984 • 22 citations

Hemolysis of human erythrocytes by paraquat in relation to superoxide dismutase activity

1979 • 22 citations

The Two-dimensional polypeptide profile of terminally non-dividing human diploid cells*1

1984 • 21 citations

Selection of conidial longevity mutants of Neurospora crassa

1984 • 21 citations

Lipofuscin Response to the 'Aging-Reversal' Drug Centrophenoxine in Rat Retinal Pigment Epithelium and Frontal Cortex

1983 • 19 citations

AGE‐RELATED CHANGES OF THYMUS – MORPHOLOGICAL and FUNCTIONAL ASPECTS –

1978 • 19 citations

Immunodeficiency in Down's syndrome: low levels of serum thymic factor in trisomic children.

1980 • 18 citations

Effects of radical-scavenging enzymes and reduced oxygen exposure on growth and chromosome abnormalities of Werner syndrome cultured skin fibroblasts

1981 • 18 citations

The Prolongation of Life: a Comparison of Antioxidants and Geroprotectors Versus Superoxide in Human Mitochondria

1981 • 18 citations

The incidence of ultrastructural abnormalities in the cortex of two retarded human brains (Down's syndrome)

1977 • 17 citations

A case of 21q-syndrome with half normal SOD-1 activity

1983 • 17 citations

Free radicals and aging. Electron spin resonance studies on neuronal lipopigments and cells grown in vitro

1983 • 16 citations

Can We Learn about Aging from a Study of Werner's Syndrome?

1982 • 15 citations

DNA REPAIR DEFECTS AND HUMAN DISEASE

1978 • 15 citations

Myocardial Protein Synthesis During Aging and Endurance Exercise in Rats

1983 • 14 citations

Further Studies on the Relationship Between Vitamin C and Thymic Humoral Factor

1971 • 13 citations

Active and Suppressor T Cells: Diminution in a Patient with Dyskeratosis Congenita and in First-Degree Relatives

1979 • 12 citations

DONOR KIDNEY SELECTION FOR TRANSPLANTATION Relationships Between Glomerular Structure, Vascular Supply and Age

1972 • 10 citations

The influence of cellular proliferative history on the susceptibility to oncogenic transformation

1981 • 9 citations

Immunological tolerance to self and non-self.

1982 • 8 citations

Immunopetentiators and the protection they give against carbon tetrachloride hepatotoxicity

1982 • 7 citations

Cell proliferation: Paths to immortality and back

1984 • 6 citations

RECOGNITION AND REGULATION BY MODIFIED SELF

1982 • 6 citations

Spontaneous mutations balance reproductive selective advantage and genetically determine longevity

1979 • 6 citations

Murine Regional Brain Monoamine Oxidase Activity: Time- and Age-Dependent Response to Inhibitors

1984 • 5 citations

EFFECTS OF DNA DAMAGING AGENTS ON CULTURED FIBROBLASTS DERIVED FROM PATIENTS WITH COCKAYNE SYNDROME

1978 • 5 citations

Sensitivity of Down's syndrome lymphocytes to mitomycin C and X-irradiation measured by sister chromatid exchange frequency

1980 • 4 citations

Deleted Work

1955 • 0 citations