Beneficial effects of intermittent fasting and caloric restriction on the cardiovascular and cerebrovascular systems.

Intermittent fasting (IF; reduced meal frequency) and caloric restriction (CR) extend lifespan and increase resistance to age-related diseases in rodents and monkeys and improve the health of overweight humans. Both IF and CR enhance cardiovascular and brain functions and improve several risk factors for coronary artery disease and stroke including a reduction in blood pressure and increased insulin sensitivity. Cardiovascular stress adaptation is improved and heart rate variability is increased in rodents maintained on an IF or a CR diet. Moreover, rodents maintained on an IF regimen exhibit increased resistance of heart and brain cells to ischemic injury in experimental models of myocardial infarction and stroke. The beneficial effects of IF and CR result from at least two mechanisms--reduced oxidative damage and increased cellular stress resistance. Recent findings suggest that some of the beneficial effects of IF on both the cardiovascular system and the brain are mediated by brain-derived neurotrophic factor signaling in the brain. Interestingly, cellular and molecular effects of IF and CR on the cardiovascular system and the brain are similar to those of regular physical exercise, suggesting shared mechanisms. A better understanding of the cellular and molecular mechanisms by which IF and CR affect the blood vessels and heart and brain cells will likely lead to novel preventative and therapeutic strategies for extending health span.

[1]  A. Baiker,et al.  VEGF is necessary for exercise‐induced adult hippocampal neurogenesis , 2003, The European journal of neuroscience.

[2]  G. Vicedomini,et al.  Early improvement of left ventricular function during caloric restriction in obesity. , 1986, International journal of obesity.

[3]  J. Stern,et al.  Calorie restriction in obesity: prevention of kidney disease in rodents. , 2001, Journal of NutriLife.

[4]  M. Dragunow,et al.  Environmental enrichment inhibits spontaneous apoptosis, prevents seizures and is neuroprotective , 1999, Nature Medicine.

[5]  L. Landsberg,et al.  Caloric restriction lowers blood pressure in the spontaneously hypertensive rat. , 1978, Metabolism: clinical and experimental.

[6]  M. Mattson,et al.  Beneficial Effects of Dietary Restriction on Cerebral Cortical Synaptic Terminals , 2000, Journal of neurochemistry.

[7]  C M McCay,et al.  The effect of retarded growth upon the length of life span and upon the ultimate body size. 1935. , 1935, Nutrition.

[8]  R. Weindruch,et al.  Caloric Intake and Aging , 1997 .

[9]  R. Jaenisch,et al.  Ischemic Brain Damage in Mice after Selectively Modifying BDNF or NT4 Gene Expression , 2000, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[10]  D. Kendall,et al.  The metabolic syndrome, type 2 diabetes, and cardiovascular disease: understanding the role of insulin resistance. , 2002, The American journal of managed care.

[11]  M. Mattson,et al.  The Endoplasmic Reticulum Stress-Responsive Protein GRP78 Protects Neurons Against Excitotoxicity and Apoptosis: Suppression of Oxidative Stress and Stabilization of Calcium Homeostasis , 1999, Experimental Neurology.

[12]  S. Goto,et al.  The effect of high altitude and caloric restriction on reactive carbonyl derivatives and activity of glutamine synthetase in rat brain. , 1998, Life sciences.

[13]  Russell,et al.  Relative role of caloric restriction and exercise training upon susceptibility to isoproterenol-induced myocardial infarction in male rats. , 1981, The American journal of clinical nutrition.

[14]  M. Mattson,et al.  Brain‐derived neurotrophic factor mediates an excitoprotective effect of dietary restriction in mice , 2001, Journal of neurochemistry.

[15]  M. Portero-Otín,et al.  Oxidative, glycoxidative and lipoxidative damage to rat heart mitochondrial proteins is lower after 4 months of caloric restriction than in age-matched controls , 2002, Mechanisms of Ageing and Development.

[16]  M. Raeini-Sarjaz,et al.  Comparison of the effect of dietary fat restriction with that of energy restriction on human lipid metabolism. , 2001, The American journal of clinical nutrition.

[17]  G. Fernandes,et al.  Food Restriction and Fish Oil Suppress Atherogenic Risk Factors in Lupus-Prone (NZB × NZW) F1 Mice , 2004, Journal of Clinical Immunology.

[18]  Sam W. Lee,et al.  Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) delays and induces escape from senescence in human dermal microvascular endothelial cells , 1997, Oncogene.

[19]  G. Freeman,et al.  Calorie restriction attenuates inflammatory responses to myocardial ischemia-reperfusion injury. , 2001, American journal of physiology. Heart and circulatory physiology.

[20]  Q Lai,et al.  Exercise pre-conditioning reduces brain damage in ischemic rats that may be associated with regional angiogenesis and cellular overexpression of neurotrophin , 2004, Neuroscience.

[21]  P. Chan Reactive Oxygen Radicals in Signaling and Damage in the Ischemic Brain , 2001, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[22]  Mark P. Mattson,et al.  Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[23]  J. Cypser,et al.  Relationship between increased longevity and stress resistance as assessed through gerontogene mutations in Caenorhabditis elegans , 2001, Experimental Gerontology.

[24]  V. Araya,et al.  [The effect of fluoxetine on insulin resistance in non diabetic obese patients]. , 1995, Revista medica de Chile.

[25]  D. Ingram,et al.  Effects of intermittent feeding upon body weight and lifespan in inbred mice: interaction of genotype and age , 1990, Mechanisms of Ageing and Development.

[26]  M. Dake,et al.  Vascular endothelial growth factor enhances atherosclerotic plaque progression , 2001, Nature Medicine.

[27]  L. Heilbronn,et al.  C-reactive protein and coronary artery disease: influence of obesity, caloric restriction and weight loss. , 2002, The Journal of nutritional biochemistry.

[28]  Anthony Gamst,et al.  Association of the Metabolic Syndrome With History of Myocardial Infarction and Stroke in the Third National Health and Nutrition Examination Survey , 2004, Circulation.

[29]  C. Padovani,et al.  Dietary restriction and fibre supplementation: oxidative stress and metabolic shifting for cardiac health. , 2003, Canadian journal of physiology and pharmacology.

[30]  R. Weindruch,et al.  Dietary restriction benefits learning and motor performance of aged mice. , 1987, Journal of gerontology.

[31]  R. Palmiter,et al.  Dbh(-/-) mice are hypotensive, have altered circadian rhythms, and have abnormal responses to dieting and stress. , 2004, American journal of physiology. Regulatory, integrative and comparative physiology.

[32]  T. Belke,et al.  Effects of chronic caloric restriction on mitochondrial respiration in the ischemic reperfused rat heart , 2002, Molecular and Cellular Biochemistry.

[33]  Mark P Mattson,et al.  GeneDiet Interactions in Brain Aging and Neurodegenerative Disorders , 2003, Annals of Internal Medicine.

[34]  E. Kouidi,et al.  Effects of athletic training on heart rate variability triangular index , 2002, Clinical physiology and functional imaging.

[35]  S. Mudaliar,et al.  Human VEGF gene expression in skeletal muscle: effect of acute normoxic and hypoxic exercise. , 1999, American journal of physiology. Heart and circulatory physiology.

[36]  D. Ingram,et al.  Calorie restriction in rhesus monkeys , 2003, Experimental Gerontology.

[37]  R. Effros,et al.  Calorie restriction inhibits the age-related dysregulation of the cytokines TNF-α and IL-6 in C3B10RF1 mice , 1997, Mechanisms of Ageing and Development.

[38]  Martin Holzenberger,et al.  IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice , 2003, Nature.

[39]  R. Weindruch,et al.  Seminars in medicine of the Beth Israel Deaconess Medical Center. Caloric intake and aging. , 1997, The New England journal of medicine.

[40]  O. Lindvall,et al.  Evidence for Neuroprotective Effects of Endogenous Brain-Derived Neurotrophic Factor after Global Forebrain Ischemia in Rats , 1999, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[41]  A. Richardson,et al.  Effect of caloric restriction on the expression of heat shock protein 70 and the activation of heat shock transcription factor 1. , 1996, Developmental genetics.

[42]  P. Bickford,et al.  Effects of dietary restriction on motor learning and cerebellar noradrenergic dysfunction in aged F344 rats , 1995, Brain Research.

[43]  T. Lue,et al.  The effect of vascular endothelial growth factor and adeno-associated virus mediated brain derived neurotrophic factor on neurogenic and vasculogenic erectile dysfunction induced by hyperlipidemia. , 2003, The Journal of urology.

[44]  G. Barja,et al.  Caloric restriction decreases mitochondrial free radical generation at complex I and lowers oxidative damage to mitochondrial DNA in the rat heart , 2001, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[45]  M. Mattson,et al.  Evidence that brain‐derived neurotrophic factor is required for basal neurogenesis and mediates, in part, the enhancement of neurogenesis by dietary restriction in the hippocampus of adult mice , 2002, Journal of neurochemistry.

[46]  C. Cotman,et al.  Exercise: a behavioral intervention to enhance brain health and plasticity , 2002, Trends in Neurosciences.

[47]  A. Koizumi,et al.  Characterization of gene expression profile associated with energy restriction‐induced cold tolerance of heart , 2002, Microscopy research and technique.

[48]  R. Weindruch,et al.  Oxidative Stress, Caloric Restriction, and Aging , 1996, Science.

[49]  M. Mattson,et al.  Modification of brain aging and neurodegenerative disorders by genes, diet, and behavior. , 2002, Physiological reviews.

[50]  M. Mattson,et al.  Paroxetine retards disease onset and progression in Huntingtin mutant mice , 2004, Annals of neurology.

[51]  H. D. Morris,et al.  Prolonged exercise induces angiogenesis and increases cerebral blood volume in primary motor cortex of the rat , 2003, Neuroscience.

[52]  J. Pipkin,et al.  Chronic caloric restriction induces stress proteins in the hypothalamus of rats , 1994, Mechanisms of Ageing and Development.

[53]  N. Mulder,et al.  Therapeutic angiogenesis with vascular endothelial growth factor in peripheral and coronary artery disease: a review , 2003, International journal of cardiovascular interventions.

[54]  R. Villareal,et al.  Heart rate variability and cardiovascular mortality , 2002, Current atherosclerosis reports.

[55]  M. Mattson,et al.  Intermittent food deprivation improves cardiovascular and neuroendocrine responses to stress in rats. , 2003, The Journal of nutrition.

[56]  Elizabeth Johnson,et al.  Mortality and morbidity in laboratory-maintained Rhesus monkeys and effects of long-term dietary restriction. , 2003, The journals of gerontology. Series A, Biological sciences and medical sciences.

[57]  M. Mattson,et al.  Dietary restriction and 2‐deoxyglucose administration reduce focal ischemic brain damage and improve behavioral outcome: Evidence for a preconditioning mechanism , 1999, Journal of neuroscience research.

[58]  E. Sugaru,et al.  Brain‐derived neurotrophic factor (BDNF) regulates glucose and energy metabolism in diabetic mice , 2002, Diabetes/metabolism research and reviews.

[59]  T. Lehtimäki,et al.  Weight Reduction With Very-Low-Caloric Diet and Endothelial Function in Overweight Adults: Role of Plasma Glucose , 2004, Arteriosclerosis, thrombosis, and vascular biology.

[60]  E. Ravussin,et al.  Calorie restriction and aging: review of the literature and implications for studies in humans. , 2003, The American journal of clinical nutrition.

[61]  M. Mattson,et al.  2‐deoxy‐d‐glucose protects hippocampal neurons against excitotoxic and oxidative injury: Evidence for the involvement of stress proteins , 1999, Journal of neuroscience research.

[62]  K. Meckling,et al.  Effects of a hypocaloric, low-carbohydrate diet on weight loss, blood lipids, blood pressure, glucose tolerance, and body composition in free-living overweight women. , 2002, Canadian journal of physiology and pharmacology.

[63]  B. Geloneze,et al.  Sibutramine enhances insulin sensitivity ameliorating metabolic parameters in a double‐blind, randomized, placebo‐controlled trial , 2003, Diabetes, obesity & metabolism.

[64]  K. Jin,et al.  VEGF-induced neuroprotection, neurogenesis, and angiogenesis after focal cerebral ischemia. , 2003, The Journal of clinical investigation.

[65]  M. Endres,et al.  Physical training increases endothelial progenitor cells, inhibits neointima formation, and enhances angiogenesis. , 2003, Circulation.

[66]  M. Mattson,et al.  Dietary supplementation with 2-deoxy-D-glucose improves cardiovascular and neuroendocrine stress adaptation in rats. , 2004, American journal of physiology. Heart and circulatory physiology.

[67]  D. Lefer,et al.  Oxidative stress and cardiac disease. , 2000, The American journal of medicine.

[68]  Stuart Maudsley,et al.  BDNF and 5-HT: a dynamic duo in age-related neuronal plasticity and neurodegenerative disorders , 2004, Trends in Neurosciences.

[69]  M. Mattson,et al.  Food restriction reduces brain damage and improves behavioral outcome following excitotoxic and metabolic insults , 1999, Annals of neurology.

[70]  M. Mattson,et al.  Reversal of behavioral and metabolic abnormalities, and insulin resistance syndrome, by dietary restriction in mice deficient in brain-derived neurotrophic factor. , 2003, Endocrinology.

[71]  T. Broderick,et al.  Caloric restriction restores the cardioprotective effect of preconditioning in the rat heart , 2002, Mechanisms of Ageing and Development.

[72]  L. Landsberg,et al.  Diet-induced changes in sympathetic nervous system activity: possible implications for obesity and hypertension. , 1982, Journal of chronic diseases.

[73]  D. Berrigan,et al.  Calorie restriction, aging, and cancer prevention: mechanisms of action and applicability to humans. , 2003, Annual review of medicine.

[74]  W. Pan,et al.  Plasma lipid profiles and epidemiology of atherosclerotic diseases in Taiwan--a unique experience. , 1995, Atherosclerosis.

[75]  R. S. Sohal,et al.  Effect of age and caloric restriction on DNA oxidative damage in different tissues of C57BL/6 mice , 1994, Mechanisms of Ageing and Development.

[76]  M. Mattson,et al.  Interactive effects of excitotoxic injury and dietary restriction on microgliosis and neurogenesis in the hippocampus of adult mice , 2007, NeuroMolecular Medicine.

[77]  Richard Weindruch,et al.  Transcriptional profiles associated with aging and middle age-onset caloric restriction in mouse hearts , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[78]  D. Mostofsky,et al.  Dietary restriction: effects on radial maze learning and lipofuscin pigment deposition in the hippocampus and frontal cortex. , 1987, Archives of gerontology and geriatrics.

[79]  Y. S. Diniz,et al.  Toxicity of ad lib. overfeeding: effects on cardiac tissue. , 2002, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.