Toward a unified theory of caloric restriction and longevity regulation

Cancer Chemopreventive Activity of Resveratrol, a Natural Product Derived from Grapes

1997 • 4,867 citations

PLEIOTROPY, NATURAL SELECTION, AND THE EVOLUTION OF SENESCENCE

1957 • 4,140 citations

Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan

2003 • 3,673 citations

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

1993 • 3,250 citations

Stress-Dependent Regulation of FOXO Transcription Factors by the SIRT1 Deacetylase

2004 • 3,100 citations

Premature ageing in mice expressing defective mitochondrial DNA polymerase

2004 • 2,561 citations

hSIR2SIRT1 Functions as an NAD-Dependent p53 Deacetylase

2001 • 2,550 citations

Modulation of NF-κB-dependent transcription and cell survival by the SIRT1 deacetylase

2004 • 2,531 citations

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

2003 • 2,209 citations

The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms

1999 • 2,199 citations

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

1935 • 2,189 citations

Visfatin: A Protein Secreted by Visceral Fat That Mimics the Effects of Insulin

2004 • 1,897 citations

Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-γ

2004 • 1,896 citations

Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans

2001 • 1,892 citations

Calorie Restriction Promotes Mammalian Cell Survival by Inducing the SIRT1 Deacetylase

2004 • 1,877 citations

Sirtuin activators mimic caloric restriction and delay ageing in metazoans

2004 • 1,847 citations

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

2000 • 1,756 citations

Flavonoid intake and risk of chronic diseases

2002 • 1,746 citations

The p66shc adaptor protein controls oxidative stress response and life span in mammals

1999 • 1,688 citations

The retardation of aging and disease by dietary restriction

1989 • 1,494 citations

Extrachromosomal rDNA Circles— A Cause of Aging in Yeast

1997 • 1,477 citations

Phylogenetic Classification of Prokaryotic and Eukaryotic Sir2-like Proteins

2000 • 1,360 citations

Mammalian SIRT1 Represses Forkhead Transcription Factors

2004 • 1,352 citations

The Endocrine Regulation of Aging by Insulin-like Signals

2003 • 1,342 citations

Sir2 mediates longevity in the fly through a pathway related to calorie restriction

2004 • 1,337 citations

Extended Longevity in Mice Lacking the Insulin Receptor in Adipose Tissue

2003 • 1,328 citations

Handbook of the Biology of Aging

1990 • 1,219 citations

The AMP-activated protein kinase cascade – a unifying system for energy control

2003 • 1,115 citations

Increased Nuclear NAD Biosynthesis and SIRT1 Activation Prevent Axonal Degeneration

2004 • 1,052 citations

Calorie restriction extends Saccharomyces cerevisiae lifespan by increasing respiration

2002 • 1,051 citations

Inhibition of Silencing and Accelerated Aging by Nicotinamide, a Putative Negative Regulator of Yeast Sir2 and Human SIRT1

2002 • 971 citations

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

1988 • 958 citations

Cloning and characterization of the cDNA encoding a novel human pre-B-cell colony-enhancing factor.

1994 • 945 citations

The NAD Biosynthesis Pathway Mediated by Nicotinamide Phosphoribosyltransferase Regulates Sir2 Activity in Mammalian Cells

2004 • 939 citations

The evolution of ageing and longevity

1979 • 875 citations

Extension of Drosophila lifespan by overexpression of human SOD1 in motorneurons

1998 • 852 citations

Resveratrol Inhibits Cyclooxygenase-2 Transcription and Activity in Phorbol Ester-treated Human Mammary Epithelial Cells

1998 • 797 citations

Characterization of Five Human cDNAs with Homology to the Yeast SIR2 Gene: Sir2-like Proteins (Sirtuins) Metabolize NAD and May Have Protein ADP-Ribosyltransferase Activity

1999 • 781 citations

Uncoupled and surviving: individual mice with high metabolism have greater mitochondrial uncoupling and live longer

2004 • 748 citations

Life-long reduction in MnSOD activity results in increased DNA damage and higher incidence of cancer but does not accelerate aging

2003 • 719 citations

Analysis of histone acetyltransferase and histone deacetylase families of Arabidopsis thaliana suggests functional diversification of chromatin modification among multicellular eukaryotes

2002 • 713 citations

Nicotinamide and PNC1 govern lifespan extension by calorie restriction in Saccharomyces cerevisiae

2003 • 706 citations

The Rate of Living.

1928 • 686 citations

DAF-16 Target Genes That Control C. elegans Life-Span and Metabolism

2003 • 644 citations

Caloric restriction and aging: an update

2000 • 616 citations

Nutritional Influences on Aging of Fischer 344 Rats: I. Physical, Metabolic, and Longevity Characteristics

1985 • 587 citations

Pre–B cell colony–enhancing factor inhibits neutrophil apoptosis in experimental inflammation and clinical sepsis

2004 • 583 citations

Acetylation of the C Terminus of Ku70 by CBP and PCAF Controls Bax-Mediated Apoptosis

2004 • 569 citations

A new role for a yeast transcriptional silencer gene, SIR2, in regulation of recombination in ribosomal DNA

1989 • 550 citations

FOXO4 Is Acetylated upon Peroxide Stress and Deacetylated by the Longevity Protein hSir2

2004 • 531 citations

Identification of a Class of Small Molecule Inhibitors of the Sirtuin Family of NAD-dependent Deacetylases by Phenotypic Screening

2001 • 524 citations

Pre-B-cell colony-enhancing factor, whose expression is up-regulated in activated lymphocytes, is a nicotinamide phosphoribosyltransferase, a cytosolic enzyme involved in NAD biosynthesis

2002 • 524 citations

Sirtuins: Sir2-related NAD-dependent protein deacetylases.

2004 • 515 citations

Resveratrol: from grapevines to mammalian biology

2003 • 508 citations

Mutation in the silencing gene S/R4 can delay aging in S. cerevisiae

1995 • 496 citations

How and why we age

1998 • 478 citations

How does calorie restriction work?

2003 • 459 citations

Genetics and the Specificity of the Aging Process

2003 • 439 citations

Modification of Brain Aging and Neurodegenerative Disorders by Genes, Diet, and Behavior

2002 • 436 citations

Sir2-Independent Life Span Extension by Calorie Restriction in Yeast

2004 • 434 citations

Extending the lifespan of long-lived mice

2001 • 425 citations

Genomic profiling of short- and long-term caloric restriction effects in the liver of aging mice

2001 • 421 citations

Oxidative Stress and Aging

2003 • 416 citations

Handbook of the Biology of Aging

2005 • 413 citations

Resveratrol, a remarkable inhibitor of ribonucleotide reductase

1998 • 387 citations

Cancer Chemopreventive Activity of Resveratrol

2002 • 386 citations

An intervention resembling caloric restriction prolongs life span and retards aging in yeast

2000 • 377 citations

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

1943 • 373 citations

Redistribution of Silencing Proteins from Telomeres to the Nucleolus Is Associated with Extension of Life Span in S. cerevisiae

1997 • 371 citations

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

1939 • 347 citations

The interaction between FOXO and SIRT1: tipping the balance towards survival

2004 • 339 citations

Identification of a small molecule inhibitor of Sir2p

2001 • 337 citations

Multiple Stressors in Caenorhabditis elegans Induce Stress Hormesis and Extended Longevity

2002 • 331 citations

Nutrition and Longevity in the Rat

1960 • 319 citations

Food, reproduction and L'ongevity: Is the extended lifespan of calorie‐restricted animals an evolutionary adaptation?

1989 • 318 citations

Fisher, Medawar, Hamilton and the Evolution of Aging

2000 • 317 citations

Selection on stress resistance increases longevity in Drosophila melanogaster

1992 • 304 citations

Silent Information Regulator 2α, a Longevity Factor and Class III Histone Deacetylase, Is an Essential Endogenous Apoptosis Inhibitor in Cardiac Myocytes

2004 • 304 citations

Molecular mechanisms linking calorie restriction and longevity

2002 • 303 citations

Lifespan extension in C. elegans by a molecular chaperone dependent upon insulin‐like signals

2003 • 300 citations

Dietary Restriction in Long-Lived Dwarf Flies

2002 • 292 citations

Expression of Heat Shock Protein 70 is Altered by Age and Diet at the Level of Transcription

1993 • 284 citations

Lifespan extension of Drosophila melanogaster through hormesis by repeated mild heat stress.

2003 • 276 citations

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

2001 • 267 citations

Old Age and Natural Death

2019 • 266 citations

Efficiency and Mechanism of the Antioxidant Action of trans-Resveratrol and Its Analogues in the Radical Liposome Oxidation

2001 • 263 citations

Temporal linkage between the phenotypic and genomic responses to caloric restriction

2004 • 261 citations

Action of food restriction in delaying the aging process.

1982 • 243 citations

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

2003 • 243 citations

Cloning and characterization of LAG1, a longevity-assurance gene in yeast.

1994 • 240 citations

Expression of heat shock protein 70 is altered by age and diet at the level of transcription.

1993 • 237 citations

MicroReview: Small molecules that regulate lifespan: evidence for xenohormesis

2004 • 234 citations

An accelerated assay for the identification of lifespan-extending interventions in Drosophila melanogaster

2004 • 232 citations

Aging in vertebrates, and the effect of caloric restriction: a mitochondrial free radical production–DNA damage mechanism?

2004 • 229 citations

Longevity Regulation inSaccharomyces cerevisiae: Linking Metabolism, Genome Stability, and Heterochromatin

2003 • 227 citations

Inhibition by red wine extract, resveratrol, of cytokine release by alveolar macrophages in COPD

2003 • 215 citations

Multiplex stress resistance in cells from long‐lived dwarf mice

2003 • 213 citations

Does food restriction retard aging by reducing the metabolic rate?

1985 • 212 citations

Thermotolerance of a Long-lived Mutant of Caenorhabditis elegans

1994 • 208 citations

Resveratrol inhibition of herpes simplex virus replication

1999 • 204 citations

Changes in Adipose Mass and Cellularity Through the Adult Life of Rats Fed Ad Libitum or a Life-Prolonging Restricted Diet

1980 • 203 citations

Axenic growth up-regulates mass-specific metabolic rate, stress resistance, and extends life span in Caenorhabditis elegans

2002 • 201 citations

Oxidative stress and mitochondrial function with aging – the effects of calorie restriction

2003 • 200 citations

Multiple-stress analysis for isolation ofDrosophilalongevity genes

2004 • 199 citations

Development of Calorie Restriction Mimetics as a Prolongevity Strategy

2004 • 199 citations

The Evolution of the Antiaging Action of Dietary Restriction: A Hypothesis

1996 • 196 citations

Effects of food restriction on aging: separation of food intake and adiposity.

1984 • 191 citations

Nicotinamide Clearance by Pnc1 Directly Regulates Sir2-Mediated Silencing and Longevity

2004 • 188 citations

Genes That Prolong Life: Relationships of Growth Hormone and Growth to Aging and Life Span

2001 • 182 citations

Ageing and apoptosis

2002 • 178 citations

Controlling caloric consumption: protocols for rodents and rhesus monkeys☆

1999 • 177 citations

Ageing-related changes in the in vivo function of rat liver macroautophagy and proteolysis

2003 • 174 citations

Larval crowding in Drosophila melanogaster induces Hsp70 expression, and leads to increased adult longevity and adult thermal stress resistance

2001 • 172 citations

Visfatin - new adipokine

2005 • 164 citations

Hormesis: from marginalization to mainstream

2004 • 161 citations

Antiangiogenic and Proapoptotic Effects of Dietary Restriction on Experimental Mouse and Human Brain Tumors

2004 • 161 citations

Additive regulation of hepatic gene expression by dwarfism and caloric restriction

2004 • 149 citations

Age‐related changes in the metabolism and body composition of three dog breeds and their relationship to life expectancy

2003 • 149 citations

Resveratrol modulates the phosphoinositide 3‐kinase pathway through an estrogen receptor α‐dependent mechanism: Relevance in cell proliferation

2003 • 149 citations

Revisiting the Role of Fat Mass in the Life Extension Induced by Caloric Restriction

1999 • 148 citations

Metabolic rate is not reduced by dietary-restriction or by lowered insulin/IGF-1 signalling and is not correlated with individual lifespan in Drosophila melanogaster

2004 • 144 citations

Hypolipidemic action of dietary resveratrol, a phytoalexin in grapes and red wine, in hepatoma-bearing rats

2003 • 143 citations

Elevated paraquat resistance can be used as a bioassay for longevity in a genetically based long‐lived strain of Drosophila

1991 • 142 citations

Testing an ‘aging gene’ in long‐lived Drosophila strains: increased longevity depends on sex and genetic background

2003 • 140 citations

Modulation of aging processes by dietary restriction

1994 • 140 citations

Intermittent fasting and dietary supplementation with 2‐deoxy‐<scp>D</scp>‐glucose improve functional and metabolic cardiovascular risk factors in rats

2003 • 138 citations

Neuroendocrine involvement in aging: Evidence from studies of reproductive aging and caloric restriction

1995 • 136 citations

Testing the Theories of Aging

1983 • 132 citations

The Occurrence of Chemically Induced Hormesis

1987 • 130 citations

Effect of Treatment with Phenformin, Diphenylhydantoin or &lt;i&gt;L&lt;/i&gt;-Dòpa on Life Span and Tumour Incidence in C3H/Sn Mice

1980 • 128 citations

Resveratrol, a red wine polyphenol, protects spinal cord from ischemia-reperfusion injury

2004 • 120 citations

Gene Expression Patterns in Calorically Restricted Mice: Partial Overlap with Long-Lived Mutant Mice

2002 • 119 citations

Synthesis of flavonoids and their effects on aldose reductase and sorbitol accumulation in streptozotocin-induced diabetic rat tissues

2001 • 118 citations

Repeated mild heat shock delays ageing in cultured human skin fibroblasts

1998 • 115 citations

Mitochondrial and nuclear DNA base excision repair are affected differently by caloric restriction

2004 • 115 citations

An in vitro model of caloric restriction

2003 • 114 citations

Effect of topically applied resveratrol on cutaneous herpes simplex virus infections in hairless mice

2003 • 113 citations

[25] Role of oxidized amino acids in protein breakdown and stability

1995 • 110 citations

Neuroprotective and neurorestorative signal transduction mechanisms in brain aging: modification by genes, diet and behavior

2002 • 110 citations

Insulin-like signaling, metabolism, stress resistance and aging in Caenorhabditis elegans

2001 • 109 citations

The effects of aging and chronic dietary restriction on whole body growth and protein turnover in the rat

1985 • 106 citations

Aging, anti-aging, and hormesis

2004 • 105 citations

Modulation of aging processes by dietary restriction

1995 • 102 citations

Understanding aging: revealing order out of chaos

2004 • 101 citations

Insulin and longevity: antidiabetic biguanides as geroprotectors.

2003 • 95 citations

Radiation Effects on Life Span in Caenorhabditis Elegans

1988 • 94 citations

Resveratrol Inhibits Cyclooxygenase‐2 Transcription in Human Mammary Epithelial Cells

1999 • 88 citations

Possible Mechanisms Underlying the Antiaging Actions of Caloric Restriction

1996 • 88 citations

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

2004 • 87 citations

Dietary Restriction Attenuates Age-Related Increases in Rat Skeletal Muscle Antioxidant Enzyme Activities

1994 • 86 citations

The beneficial effects of dietary restriction: reduced oxidative damage and enhanced apoptosis

1996 • 86 citations

The Role of Fat Depletion in the Biological Benefits of Caloric Restriction

2001 • 86 citations

Effect of metformin on fatty acid and glucose metabolism in freshly isolated hepatocytes and on specific gene expression in cultured hepatocytes11Abbreviations: CPT I or II, carnitine palmitoyltransferase I or II; mtHMG-CoA synthase, mitochondrial hydroxymethylglutaryl-CoA synthase; Glc-6-Pase, glucose-6-phosphatase; PEPCK, phosphoenolpyruvate carboxykinase; GK, glucokinase; L-PK, liver-type pyruvate kinase; and ACS, acyl-CoA synthetase.

2001 • 86 citations

Stress resistance and longevity in selected lines of Drosophila melanogaster☆

1999 • 85 citations

Expression of the Pro-apoptotic Genegadd153/chop Is Elevated in Liver with Aging and Sensitizes Cells to Oxidant Injury

2003 • 82 citations

Calorie restriction increases cell surface GLUT-4 in insulin-stimulated skeletal muscle

1998 • 81 citations

Neuroendocrine and Pharmacological Manipulations to Assess How Caloric Restriction Increases Life Span

2001 • 80 citations

Chronic activation of AMP-activated kinase as a strategy for slowing aging

2004 • 78 citations

Antioxidant status and stress resistance in long- and short-lived lines of Drosophila melanogaster

2001 • 78 citations

Caloric restriction and lifespan: a role for protein turnover?

2002 • 78 citations

THE JOURNAL OF NUTRITION: RETARDED GROWTH, LIFE SPAN, ULTIMATE BODY SIZE AND AGE CHANGES IN THE ALBINO RAT AFTER FEEDING DIETS RESTRICTED IN CALORIES

2009 • 76 citations

Effect of diet restriction on glucose metabolism and insulin responsiveness in aging rats

1988 • 75 citations

Assessing metabolic activity in aging Caenorhabditis elegans: concepts and controversies

2002 • 75 citations

Suppression of apoptosis by calorie restriction in aged kidney

2004 • 70 citations

Adaptation of muscle glucose transport with caloric restriction in adult, middle-aged, and old rats

1994 • 69 citations

Prolongation of the Life of Drosophila subobscura by a Brief Exposure of Adults to a High Temperature

1958 • 68 citations

Hormesis and debilitation effects in stress experiments using the nematode worm Caenorhabditis elegans: the model of balance between cell damage and HSP levels

2001 • 67 citations

Effects of age and food restriction on oxidative DNA damage and antioxidant enzyme activities in the mouse aorta

2001 • 67 citations

Upregulation of apoptosis with dietary restriction: implications for carcinogenesis and aging.

1998 • 66 citations

The effects of different levels of dietary restriction on aging and survival in the Sprague-Dawley rat: Implications for chronic studies

2001 • 66 citations

Life‐long calorie restriction (CR) increases expression of apoptosis repressor with a caspase recruitment domain (ARC) in the brain

2003 • 65 citations

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

1998 • 63 citations

Plasmid Accumulation Reduces Life Span in Saccharomyces cerevisiae

2003 • 62 citations

Ability of insulin to modulate hepatic glucose production in aging rats is impaired by fat accumulation

2000 • 60 citations

Divergent Effects of Caloric Restriction on Gene Expression in Normal and Long-Lived Mice

2004 • 58 citations

Inhibition of cell transformation by resveratrol and its derivatives: differential effects and mechanisms involved

2003 • 57 citations

Heating stress patterns in Caenorhabditis elegans longevity and survivorship.

2001 • 57 citations

Ageing and survival after different doses of heat shock: the results of analysis of data from stress experiments with the nematode worm Caenorhabditis elegans

2001 • 56 citations

Effect of carnosine on Drosophila melanogaster lifespan.

2002 • 52 citations

Antioxidant enzyme activities in lens, liver and kidney of calorie restricted Emory mice

1997 • 49 citations

Dietary restriction attenuates the neuronal loss, induction of heme oxygenase-1 and blood–brain barrier breakdown induced by impaired oxidative metabolism

2000 • 49 citations

Geroprotector effectiveness of melatonin: investigation of lifespan of Drosophila melanogaster

1999 • 48 citations

Hormesis in Caenorhabditis elegans dauer-defective mutants.

2003 • 48 citations

Does caloric restriction induce hormesis?

2000 • 47 citations

Dietary supplementation with 2-deoxy-<scp>d</scp>-glucose improves cardiovascular and neuroendocrine stress adaptation in rats

2004 • 43 citations

Measurement of the 4,834‐bp Mitochondrial DNA Deletion Level in Aging Rat Liver and Brain Subjected or Not to Caloric Restriction Diet

2004 • 42 citations

Impact of aging and life-long calorie restriction on expression of apoptosis-related genes in male F344 rat liver

2002 • 42 citations

Resveratrol protects against 4‐HNE induced oxidative stress and apoptosis in Swiss 3T3 fibroblasts

2004 • 41 citations

Effects of Age and Caloric Restriction on Brain Neuronal Cell Death/Survival

2004 • 38 citations

Effect of epitalon on the lifespan increase in Drosophila melanogaster

2000 • 37 citations

Aging and Restriction of Dietary Calories Increases Insulin Receptor mRNA, and Aging Increases Glucocorticoid Receptor MRNA in the Liver of Female C3B10RF1 Mice

1991 • 37 citations

HSP70 induction may explain the long-lasting resistance to heat of Drosophila melanogaster having lived in hypergravity

1999 • 35 citations

Antiaging Action of Caloric Restriction: Endocrine and Metabolic Aspects

1995 • 34 citations

Inhibition of tumor necrosis factor‐induced apoptosis in transgenic mouse liver expressing creatine kinase

2004 • 34 citations

Hormetic Mechanisms of Anti-Aging and Rejuvenating Effects of Repeated Mild Heat Stress on Human Fibroblasts in Vitro

2004 • 33 citations

Relationship Between Lipid Peroxidation, Fatty Acid Composition, and Ascorbic Acid in the Liver During Carbohydrate and Caloric Restriction in Mice

1993 • 33 citations

Comparison of the effects of 20 days and 15 months of calorie restriction on male Fischer 344 rats

1998 • 30 citations

Hypergravity and aging in Drosophila melanogaster: 7. New longevity data

1993 • 26 citations

Diet and ageing: the possible relation to reactive oxygen species.

1999 • 25 citations

Short-term caloric restriction and regulatory proteins of apoptosis in heart, skeletal muscle and kidney of Fischer 344 rats.

2003 • 25 citations

Potential Role of the Modulation of Fuel Use in the Antiaging Action of Dietary Restriction

1992 • 22 citations

Hormesis - Implications for risk assessment caloric intake (body weight) as an exemplar

1998 • 21 citations

Environmental factors in aging and mortality

1967 • 20 citations

Does Caloric Restriction in the Laboratory Simply Prevent Overfeeding and Return House Mice to Their Natural Level of Food Intake?

2001 • 19 citations

Dietary Restriction, Hormesis, and Small Molecule Mimetics

2005 • 15 citations

Radioresistance and Longevity of Inbred Lines ofDrosophila Melanogaster

1972 • 15 citations

Tipping the Balance toward Longevity

2004 • 14 citations

Selective alteration of DNA fragmentation and caspase activity in the spinal cord of aged rats and effect of dietary restriction

2003 • 13 citations

Stress Resistance ofDrosophilaTransgenic for Bovine CuZn Superoxide Dismutase

1992 • 13 citations

Aging increases DNase γ, an apoptosis-related endonuclease, in rat liver nuclei: effect of dietary restriction

2003 • 10 citations

Genotoxicity of tacrine in primary hepatocytes isolated from B6C3F1 mice and aged ad libitum and calorie restricted Fischer 344 rats

1995 • 10 citations

Re-adaptation hypothesis: explaining health benefits of caloric restriction

2004 • 8 citations

Upregulation of Apoptosis with Dietary Restriction: Implications for Carcinogenesis and Aging

1998 • 7 citations

Yeast aging research: recent advances and medical relevance

1999 • 7 citations

Paraquat resistance and starvation conditions in the selection for longevity extremes in drosophila melanogaster populations previously selected for long and short developmental period

1995 • 6 citations