How increased oxidative stress promotes longevity and metabolic health: The concept of mitochondrial hormesis (mitohormesis)

Aging: A Theory Based on Free Radical and Radiation Chemistry

1956 • 8,252 citations

Health benefits of physical activity: the evidence

2006 • 7,336 citations

TOR Signaling in Growth and Metabolism

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AMPK Phosphorylation of Raptor Mediates a Metabolic Checkpoint

2008 • 3,474 citations

A C. elegans mutant that lives twice as long as wild type

1993 • 3,250 citations

Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans

2003 • 2,209 citations

Mortality in Randomized Trials of Antioxidant Supplements for Primary and Secondary Prevention

2007 • 2,208 citations

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

1935 • 2,189 citations

daf-2 , an Insulin Receptor-Like Gene That Regulates Longevity and Diapause in Caenorhabditis elegans

1997 • 2,174 citations

Exercise-Induced Oxidative Stress: Cellular Mechanisms and Impact on Muscle Force Production

2008 • 2,164 citations

Caloric Restriction Delays Disease Onset and Mortality in Rhesus Monkeys

2009 • 2,152 citations

IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice

2002 • 2,057 citations

Effect of Selenium and Vitamin E on Risk of Prostate Cancer and Other Cancers

2008 • 2,034 citations

Requirement of NAD and SIR2 for Life-Span Extension by Calorie Restriction in Saccharomyces cerevisiae

2000 • 1,756 citations

Free radicals and tissue damage produced by exercise

1982 • 1,754 citations

A Mutant Drosophila Insulin Receptor Homolog That Extends Life-Span and Impairs Neuroendocrine Function

2001 • 1,583 citations

Hydrogen Peroxide Sensing and Signaling

2007 • 1,539 citations

The retardation of aging and disease by dietary restriction

1989 • 1,494 citations

Antioxidants prevent health-promoting effects of physical exercise in humans

2009 • 1,466 citations

Extension of Life-Span by Overexpression of Superoxide Dismutase and Catalase in Drosophila melanogaster

1994 • 1,461 citations

Mitochondrial complex III is required for hypoxia-induced ROS production and cellular oxygen sensing

2005 • 1,425 citations

MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20 536 high-risk individuals: a randomised placebo-controlled trial

2002 • 1,394 citations

Extended Longevity in Mice Lacking the Insulin Receptor in Adipose Tissue

2003 • 1,328 citations

A Muscle-Specific Insulin Receptor Knockout Exhibits Features of the Metabolic Syndrome of NIDDM without Altering Glucose Tolerance

1998 • 1,173 citations

Effects of Long-term Vitamin E Supplementation on Cardiovascular Events and Cancer

2005 • 1,160 citations

Glucose Restriction Extends Caenorhabditis elegans Life Span by Inducing Mitochondrial Respiration and Increasing Oxidative Stress

2007 • 1,155 citations

Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-analysis of randomised trials

2003 • 1,094 citations

Calorie Restriction Promotes Mitochondrial Biogenesis by Inducing the Expression of eNOS

2005 • 1,075 citations

Calorie restriction extends Saccharomyces cerevisiae lifespan by increasing respiration

2002 • 1,051 citations

MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20536 high-risk individuals: a randomised placebo-controlled trial

2002 • 1,028 citations

Effects of Low-Carbohydrate vs Low-Fat Diets on Weight Loss and Cardiovascular Risk Factors

2006 • 961 citations

A mutation in the age-1 gene in Caenorhabditis elegans lengthens life and reduces hermaphrodite fertility.

1988 • 958 citations

Extension of chronological life span in yeast by decreased TOR pathway signaling

2006 • 939 citations

Effect of 6-Month Calorie Restriction on Biomarkers of Longevity, Metabolic Adaptation, and Oxidative Stress in Overweight Individuals

2006 • 925 citations

The genetics of caloric restriction in Caenorhabditis elegans

1998 • 918 citations

Insulin Action, Diabetogenes, and the Cause of Type II Diabetes

1994 • 914 citations

Extension of Life-Span with Superoxide Dismutase/Catalase Mimetics

2000 • 909 citations

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1996 • 884 citations

Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans

2004 • 874 citations

Vitamins E and C in the Prevention of Cardiovascular Disease in Men

2008 • 866 citations

Extension of Drosophila lifespan by overexpression of human SOD1 in motorneurons

1998 • 852 citations

Thermotolerance and extended life-span conferred by single-gene mutations and induced by thermal stress.

1995 • 847 citations

Oxygen sensing by mitochondria at complex III: the paradox of increased reactive oxygen species during hypoxia

2006 • 829 citations

AMP‐activated protein kinase – development of the energy sensor concept

2006 • 791 citations

Oral administration of vitamin C decreases muscle mitochondrial biogenesis and hampers training-induced adaptations in endurance performance

2008 • 780 citations

LOCALIZATION OF THE PRIMARY METABOLIC BLOCK PRODUCED BY 2-DEOXYGLUCOSE

1957 • 777 citations

A Clinical Trial of Antioxidant Vitamins to Prevent Colorectal Adenoma

1994 • 769 citations

An AMPK-FOXO Pathway Mediates Longevity Induced by a Novel Method of Dietary Restriction in C. elegans

2007 • 751 citations

Amino-acid imbalance explains extension of lifespan by dietary restriction in Drosophila

2009 • 735 citations

Thedaf‐2gene network for longevity regulates oxidative stress resistance and Mn‐superoxide dismutase gene expression inCaenorhabditis elegans

1999 • 721 citations

Biological stress response terminology: Integrating the concepts of adaptive response and preconditioning stress within a hormetic dose–response framework

2007 • 700 citations

FROM MICE TO MEN: Insights into the Insulin Resistance Syndromes

2005 • 699 citations

Methionine‐deficient diet extends mouse lifespan, slows immune and lens aging, alters glucose, T4, IGF‐I and insulin levels, and increases hepatocyte MIF levels and stress resistance

2005 • 696 citations

Calorie restriction and aging: review of the literature and implications for studies in humans

2003 • 691 citations

Calorie restriction induces mitochondrial biogenesis and bioenergetic efficiency

2006 • 664 citations

Methionine sulfoxide reductase (MsrA) is a regulator of antioxidant defense and lifespan in mammals

2001 • 642 citations

Caloric restriction and aging: an update

2000 • 616 citations

The AMP-activated protein kinase AAK-2 links energy levels and insulin-like signals to lifespan in C. elegans

2004 • 610 citations

Antioxidant supplements for prevention of gastrointestinal cancers: a systematic review and meta-analysis

2004 • 607 citations

Daily Activity Energy Expenditure and Mortality Among Older Adults

2006 • 590 citations

Mitochondrial disease in superoxide dismutase 2 mutant mice

1999 • 581 citations

Toward a unified theory of caloric restriction and longevity regulation

2005 • 568 citations

Reactive Oxygen Species Enhance Insulin Sensitivity

2009 • 554 citations

Endurance Exercise as a Countermeasure for Aging

2008 • 543 citations

Evidence for lifespan extension and delayed age–related biomarkers in insulin receptor substrate 1 null mice

2007 • 531 citations

4E-BP Extends Lifespan upon Dietary Restriction by Enhancing Mitochondrial Activity in Drosophila

2009 • 523 citations

Brain IRS2 Signaling Coordinates Life Span and Nutrient Homeostasis

2007 • 515 citations

Quality control of mitochondria: protection against neurodegeneration and ageing

2008 • 511 citations

Calories Do Not Explain Extension of Life Span by Dietary Restriction in Drosophila

2005 • 509 citations

Aging, Adiposity, and Calorie Restriction

2007 • 501 citations

Deletion of the Mitochondrial Superoxide Dismutase sod-2 Extends Lifespan in Caenorhabditis elegans

2009 • 476 citations

A Randomized Factorial Trial of Vitamins C and E and Beta Carotene in the Secondary Prevention of Cardiovascular Events in Women

2007 • 470 citations

Reduced IGF-1 Signaling Delays Age-Associated Proteotoxicity in Mice

2009 • 465 citations

Against the oxidative damage theory of aging: superoxide dismutases protect against oxidative stress but have little or no effect on life span in Caenorhabditis elegans

2008 • 460 citations

Overexpression of Catalase Targeted to Mitochondria Attenuates Murine Cardiac Aging

2009 • 453 citations

Should Supplemental Antioxidant Administration Be Avoided During Chemotherapy and Radiation Therapy?

2008 • 451 citations

Sirtuins as potential targets for metabolic syndrome

2006 • 445 citations

2-Deoxy-D-glucose reduces epilepsy progression by NRSF-CtBP–dependent metabolic regulation of chromatin structure

2006 • 442 citations

High-quality life extension by the enzyme peptide methionine sulfoxide reductase

2002 • 440 citations

Sir2-Independent Life Span Extension by Calorie Restriction in Yeast

2004 • 434 citations

Extending the lifespan of long-lived mice

2001 • 425 citations

Reduced TOR Signaling Extends Chronological Life Span via Increased Respiration and Upregulation of Mitochondrial Gene Expression

2007 • 421 citations

Genetic links between diet and lifespan: shared mechanisms from yeast to humans

2007 • 415 citations

Calorie restriction mimetics: an emerging research field

2006 • 403 citations

Primary Prevention of Cardiovascular Events With Low-Dose Aspirin and Vitamin E in Type 2 Diabetic Patients

2003 • 387 citations

Systematic review of randomized controlled trials of low‐carbohydrate vs. low‐fat/low‐calorie diets in the management of obesity and its comorbidities

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Dietary restriction and 2‐deoxyglucose administration improve behavioral outcome and reduce degeneration of dopaminergic neurons in models of Parkinson's disease

1999 • 385 citations

Glucose Intolerance and Aging

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Null mutation of copper/zinc superoxide dismutase in Drosophila confers hypersensitivity to paraquat and reduced longevity.

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Effects of extract of western red-cedar heartwood on certain wood-decaying fungi in culture

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Distinct mitochondrial retrograde signals control the G1-S cell cycle checkpoint

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Mitochondrial dysfunction as a cause of ageing

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Cellular Regulation by Hydrogen Peroxide

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Endocrine regulation of ageing

2007 • 345 citations

Reduced insulin/IGF‐1 signalling and human longevity

2005 • 344 citations

Association of common genetic variation in the insulin/IGF1 signaling pathway with human longevity

2009 • 343 citations

High oxidative damage levels in the longest‐living rodent, the naked mole‐rat

2006 • 342 citations

Glucose Shortens the Life Span of C. elegans by Downregulating DAF-16/FOXO Activity and Aquaporin Gene Expression

2009 • 336 citations

Quantitative Mass Spectrometry Identifies Insulin Signaling Targets in C. elegans

2007 • 324 citations

Higher Respiratory Activity Decreases Mitochondrial Reactive Oxygen Release and Increases Life Span in Saccharomyces cerevisiae

2004 • 317 citations

Targeted disruption of growth hormone receptor interferes with the beneficial actions of calorie restriction

2006 • 311 citations

Dietary Restriction in Long-Lived Dwarf Flies

2002 • 292 citations

Vitamins C and E and Beta Carotene Supplementation and Cancer Risk: A Randomized Controlled Trial

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Plasma antioxidant status and cell injury after severe physical exercise

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Influences of Dietary Restriction and Age on Liver Enzyme Activities and Lipid Peroxidation in Mice

1987 • 280 citations

Superoxide Dismutase and Catalase in Skeletal Muscle: Adaptive Response to Exercise

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Brain IGF-1 Receptors Control Mammalian Growth and Lifespan through a Neuroendocrine Mechanism

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Nutritional control of aging

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Minireview: The Role of Oxidative Stress in Relation to Caloric Restriction and Longevity

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C. elegans as Model for the Study of High Glucose– Mediated Life Span Reduction

2009 • 268 citations

Protein oxidation associated with aging is reduced by dietary restriction of protein or calories.

1992 • 248 citations

The mitochondrial impairment, oxidative stress and neurodegeneration connection: reality or just an attractive hypothesis?

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Life extension via dietary restriction is independent of the Ins/IGF-1 signalling pathway in Caenorhabditis elegans

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Action of food restriction in delaying the aging process.

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Mitochondrial energy metabolism and ageing

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Mitochondrial H2O2 Regulates the Angiogenic Phenotype via PTEN Oxidation

2005 • 240 citations

Long-Lived Growth Hormone Receptor Knockout Mice: Interaction of Reduced Insulin-Like Growth Factor I/Insulin Signaling and Caloric Restriction

2004 • 233 citations

Effects of a potent antioxidant, platinum nanoparticle, on the lifespan of Caenorhabditis elegans

2008 • 228 citations

A Randomized Trial of Antioxidant Vitamins to Prevent Second Primary Cancers in Head and Neck Cancer Patients

2005 • 224 citations

Sublethal mitochondrial stress with an attendant stoichiometric augmentation of reactive oxygen species may precipitate many of the beneficial alterations in cellular physiology produced by caloric restriction, intermittent fasting, exercise and dietary phytonutrients: “Mitohormesis” for health and vitality

2005 • 221 citations

The cellular basis for diverse responses to oxygen

2006 • 219 citations

Diet and Aging

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Ubiquitous overexpression of CuZn superoxide dismutase does not extendlife span in mice

2000 • 214 citations

Calorie restriction extends the chronological lifespan of Saccharomyces cerevisiae independently of the Sirtuins

2007 • 211 citations

Effect of Dietary Restriction on the Age-Dependent Changes in the Expression of Antioxidant Enzymes in Rat Liver

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Living Fast, Dying When? The Link between Aging and Energetics

2002 • 202 citations

Minireview: Implication of Mitochondria in Insulin Secretion and Action

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Development of Calorie Restriction Mimetics as a Prolongevity Strategy

2004 • 199 citations

Overexpression of Mn Superoxide Dismutase Does Not Increase Life Span in Mice

2009 • 198 citations

The coordination of nuclear and mitochondrial communication during aging and calorie restriction

2009 • 198 citations

Mice Deficient in Both Mn Superoxide Dismutase and Glutathione Peroxidase-1 Have Increased Oxidative Damage and a Greater Incidence of Pathology but No Reduction in Longevity

2009 • 192 citations

Coenzyme Q10 can prolong C. elegans lifespan by lowering oxidative stress

2003 • 191 citations

Drosophila lifespan control by dietary restriction independent of insulin‐like signaling

2008 • 188 citations

Increased Life Span due to Calorie Restriction in Respiratory-Deficient Yeast

2005 • 187 citations

Reduction in Glutathione Peroxidase 4 Increases Life Span Through Increased Sensitivity to Apoptosis

2007 • 182 citations

Genetic modifiers of the phenotype of mice deficient in mitochondrial superoxide dismutase

2006 • 182 citations

A carboxyfullerene SOD mimetic improves cognition and extends the lifespan of mice

2006 • 181 citations

Efficacy of Antioxidant Supplementation in Reducing Primary Cancer Incidence and Mortality: Systematic Review and Meta-analysis

2008 • 179 citations

Changes in the expression of superoxide dismutase and catalase as a function of age and dietary restriction

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Activities of antioxidant enzymes in various tissues of male Fischer 344 rats are altered by food restriction.

1995 • 170 citations

The mitochondrial theory of aging: Insight from transgenic and knockout mouse models

2009 • 170 citations

Effects of caloric restriction on mitochondrial function and gene transcripts in rat muscle

2002 • 170 citations

Antioxidant Supplementation Increases the Risk of Skin Cancers in Women but Not in Men

2007 • 167 citations

Deletion of the Intestinal Peptide Transporter Affects Insulin and TOR Signaling in Caenorhabditis elegans

2004 • 167 citations

Effect of vitamin E on lifespan and reproduction in Caenorhabditis elegans

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Hormesis and the Antiaging Action of Dietary Restriction

1998 • 166 citations

Converging Pathways in Lifespan Regulation

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Self-report of physical activity and patterns of mortality in seventh-day adventist men

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The gerontogenes age‐1 and daf‐2 determine metabolic rate potential in aging Caenorhabditis elegans

1995 • 159 citations

Effects of vitamins C and E and β-carotene on the risk of type 2 diabetes in women at high risk of cardiovascular disease: a randomized controlled trial

2009 • 156 citations

Caenorhabditis elegans lifespan extension caused by treatment with an orally active ROS-generator is dependent on DAF-16 and SIR-2.1

2009 • 155 citations

Antioxidant supplementation does not affect fasting plasma glucose in the Supplementation with Antioxidant Vitamins and Minerals (SU.VI.MAX) study in France: association with dietary intake and plasma concentrations 1–3

2006 • 152 citations

Effects of antioxidant supplements on cancer prevention: meta-analysis of randomized controlled trials

2009 • 152 citations

Effects of Long-Term Daily Low-Dose Supplementation With Antioxidant Vitamins and Minerals on Structure and Function of Large Arteries

2004 • 150 citations

Effects of Tocotrienols on Life Span and Protein Carbonylation in Caenorhabditis elegans

2000 • 142 citations

The effect of vitamin E on blood pressure in individuals with type 2 diabetes: a randomized, double-blind, placebo-controlled trial

2006 • 141 citations

2-Deoxyglucose as an Energy Restriction Mimetic Agent: Effects on Mammary Carcinogenesis and on Mammary Tumor Cell Growth In vitro

2005 • 139 citations

Alterations in Oxygen Consumption, Respiratory Quotient, and Heat Production in Long-Lived GHRKO and Ames Dwarf Mice, and Short-Lived bGH Transgenic Mice

2009 • 138 citations

Mitochondrial gene expression and increased oxidative metabolism: role in increased lifespan of fat‐specific insulin receptor knock‐out mice

2007 • 137 citations

Restriction of amino acids extends lifespan in Drosophila melanogaster

2006 • 133 citations

Oxidative metabolism in cancer growth

2006 • 132 citations

Long-term β-Carotene Supplementation and Risk of Type 2 Diabetes Mellitus

1999 • 131 citations

Hormesis/preconditioning mechanisms, the nervous system and aging

2006 • 129 citations

No reduction of metabolic rate in food restricted Caenorhabditis elegans

2002 • 129 citations

Defective Mitochondrial Gene Expression Results in Reactive Oxygen Species-Mediated Inhibition of Respiration and Reduction of Yeast Life Span

2006 • 128 citations

Targeted disruption of hepatic frataxin expression causes impaired mitochondrial function, decreased life span and tumor growth in mice

2005 • 128 citations

The rate of living : being an account of some experimental studies on the biology of life duration

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Disruption of Growth Hormone Receptor Prevents Calorie Restriction from Improving Insulin Action and Longevity

2009 • 124 citations

Premature ageing in transgenic mice expressing different growth hormone genes.

1993 • 121 citations

GLUT4 glucose transporter deficiency increases hepatic lipid production and peripheral lipid utilization

2004 • 120 citations

No increase in lifespan in Caenorhabditis elegans upon treatment with the superoxide dismutase mimetic EUK-8

2003 • 116 citations

2-Deoxy-D-Glucose Feeding in Rats Mimics Physiologic Effects of Calorie Restriction

1998 • 115 citations

The trifecta of aging in Caenorhabditis elegans

2006 • 114 citations

Effects of Growth Hormone and Insulin-Like Growth Factor-1 on Hepatocyte Antioxidative Enzymes

2002 • 112 citations

Distinct pathways of insulin-regulated versus diabetes-regulated gene expression: Anin vivoanalysis in MIRKO mice

2004 • 108 citations

Energy expenditure of calorically restricted rats is higher than predicted from their altered body composition

2005 • 107 citations

GLUT4 glucose transporter deficiency increases hepatic lipid production and peripheral lipid utilization

2004 • 106 citations

Pro-Aging Effects of Glucose Signaling through a G Protein-Coupled Glucose Receptor in Fission Yeast

2009 • 99 citations

Ageing in nematodes: do antioxidants extend lifespan in Caenorhabditis elegans?

2009 • 94 citations

The potential for dietary restriction to increase longevity in humans: extrapolation from monkey studies

2006 • 90 citations

Reversal of the Mitochondrial Phenotype and Slow Development of Oxidative Biomarkers of Aging in Long-lived Mclk1+/− Mice

2009 • 89 citations

Preadaptation to efficient respiratory maintenance is essential both for maximal longevity and the retention of replicative potential in chronologically ageing yeast

2006 • 89 citations

Life-long vitamin C supplementation in combination with cold exposure does not affect oxidative damage or lifespan in mice, but decreases expression of antioxidant protection genes

2006 • 89 citations

Lack of Correlation between Mitochondrial Reactive Oxygen Species Production and Life Span in Drosophila

2004 • 87 citations

Effects of supplemental alpha-tocopherol and beta-carotene on urinary tract cancer: incidence and mortality in a controlled trial (Finland).

2000 • 86 citations

Effect of α-tocopherol and β-carotene supplementation on the incidence of type 2 diabetes

2007 • 84 citations

The effects of supplementation with alpha-tocopherol and beta-carotene on the incidence and mortality of carcinoma of the pancreas in a randomized, controlled trial.

1999 • 84 citations

Is there a role for supplemented antioxidants in the prevention of atherosclerosis?

2008 • 83 citations

Effect of supplementation with antioxidants upon long-term risk of hypertension in the SU.VI.MAX study: association with plasma antioxidant levels

2005 • 78 citations

Caloric restriction augments ROS defense inS. cerevisiae, by a Sir2p independent mechanism

2004 • 76 citations

Effects of superoxide dismutase/catalase mimetics on life span and oxidative stress resistance in the housefly, Musca domestica

2002 • 75 citations

Decrease in cellular replicative potential in “giant” mice transfected with the bovine growth hormone gene correlates to shortened life span

1993 • 73 citations

A method for oral administration of hydrophilic substances to Caenorhabditis elegans: Effects of oral supplementation with antioxidants on the nematode lifespan

2009 • 68 citations

The effects of supplementation with ?-tocopherol and ?-carotene on the incidence and mortality of carcinoma of the pancreas in a randomized, controlled trial

1999 • 65 citations

Influence of caloric intake on aging and on the response to stressors

1998 • 63 citations

The diet restriction paradigm: a brief review of the effects of every-other-day feeding

2005 • 62 citations

Metabolism, physiology and stress defense in three aging Ins/IGF‐1 mutants of the nematode Caenorhabditis elegans

2005 • 62 citations

Impaired respiration is positively correlated with decreased life span inCaenorhabditis elegansmodels of Friedreich Ataxia

2007 • 55 citations

Comparative approaches to facilitate the discovery of prolongevity interventions: Effects of tocopherols on lifespan of three invertebrate species

2006 • 55 citations

SOD isoforms play no role in lifespan in ad lib or dietary restricted conditions, but mutational inactivation of SOD-1 reduces life extension by cold

2008 • 52 citations

Murine Models of Life Span Extension

2004 • 50 citations

Low Utilization of Circulating Glucose after Food Withdrawal in Snell Dwarf Mice

2007 • 45 citations

Food restriction in female Wistar rats: V. Lipid peroxidation and antioxidant enzymes in the liver

1992 • 45 citations

Commentary: Oxygen Radicals, A Failure Or A Success of Evolution?

1993 • 45 citations

Some biochemical parameters of ageing in relation to dietary protein

1983 • 44 citations

Effect of Short-Term Ketogenic Diet on Redox Status of Human Blood

2007 • 44 citations

Plasma Glucose and the Action of Calorie Restriction on Aging

2007 • 40 citations

Mrg19 depletion increases S. cerevisiae lifespan by augmenting ROS defence

2005 • 39 citations

Antioxidant supplementation does not affect fasting plasma glucose in the Supplementation with Antioxidant Vitamins and Minerals (SU.VI.MAX) study in France: association with dietary intake and plasma concentrations

2006 • 37 citations

Increasing longevity by tuning up metabolism

2005 • 32 citations

Evidence for only two independent pathways for decreasing senescence in Caenorhabditis elegans

2009 • 27 citations

Will dietary restriction work in primates?

2006 • 22 citations