Mechanisms of vascular aging: new perspectives.

This review focuses on molecular, cellular, and functional changes that occur in the vasculature during aging; explores the links between mitochondrial oxidative stress, inflammation, and development of vascular disease in the elderly patients; and provides a landscape of molecular mechanisms involved in cellular oxidative stress resistance, which could be targeted for the prevention or amelioration of unsuccessful vascular aging. Practical interventions for prevention of age-associated vascular dysfunction and disease in old age are considered here based on emerging knowledge of the effects of anti-inflammatory treatments, regular exercise, dietary interventions, and caloric restriction mimetics.

[1]  C. Bearzi,et al.  Identification of a coronary vascular progenitor cell in the human heart , 2009, Proceedings of the National Academy of Sciences.

[2]  M. Delp,et al.  Effects of ageing and exercise training on eNOS uncoupling in skeletal muscle resistance arterioles , 2009, The Journal of physiology.

[3]  D. Riddle,et al.  Adult‐onset deficiency in growth hormone and insulin‐like growth factor‐I alters oligodendrocyte turnover in the corpus callosum , 2009, Glia.

[4]  K. Pearson,et al.  Anti-oxidative and anti-inflammatory vasoprotective effects of caloric restriction in aging: Role of circulating factors and SIRT1 , 2009, Mechanisms of Ageing and Development.

[5]  Zheng-Ping Yu,et al.  Young environment reverses the declined activity of aged rat-derived endothelial progenitor cells: involvement of the phosphatidylinositol 3-kinase/Akt signaling pathway. , 2009, Annals of vascular surgery.

[6]  D. Seals,et al.  Voluntary wheel running restores endothelial function in conduit arteries of old mice: direct evidence for reduced oxidative stress, increased superoxide dismutase activity and down‐regulation of NADPH oxidase , 2009, The Journal of physiology.

[7]  Z. Ungvari,et al.  Resveratrol induces mitochondrial biogenesis in endothelial cells , 2009, American journal of physiology. Heart and circulatory physiology.

[8]  Daniel W Trott,et al.  Exercise training reverses age-related decrements in endothelium-dependent dilation in skeletal muscle feed arteries. , 2009, Journal of applied physiology.

[9]  B. Herbert,et al.  Premature senescence of highly proliferative endothelial progenitor cells is induced by tumor necrosis factor‐α via the p38 mitogen‐activated protein kinase pathway , 2009, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[10]  G. Reed,et al.  Vascular Disease in Mice With a Dysfunctional Circadian Clock , 2009, Circulation.

[11]  Z. Ungvari,et al.  The Krebs cycle and mitochondrial mass are early victims of endothelial dysfunction: proteomic approach. , 2009, The American journal of pathology.

[12]  S. Kihara,et al.  Caloric Restriction Stimulates Revascularization in Response to Ischemia via Adiponectin-mediated Activation of Endothelial Nitric-oxide Synthase* , 2009, Journal of Biological Chemistry.

[13]  K. Pearson,et al.  Anti-oxidative and anti-inflammatory vasoprotective effects of caloric restriction in aging : role of circulating factors and SIRT 1 , 2009 .

[14]  L. Ferrucci,et al.  Serum carboxymethyl-lysine, an advanced glycation end product, is associated with increased aortic pulse wave velocity in adults. , 2009, American journal of hypertension.

[15]  Z. Ungvari,et al.  Oxidative stress and accelerated vascular aging: implications for cigarette smoking. , 2009, Frontiers in bioscience.

[16]  J. Erusalimsky.  Vascular endothelial senescence: from mechanisms to pathophysiology. , 2009, Journal of applied physiology.

[17]  N. D. Kim,et al.  Effect of short term calorie restriction on pro-inflammatory NF-kB and AP-1 in aged rat kidney , 2009, Inflammation Research.

[18]  D. Seals,et al.  Aging is associated with greater nuclear NFκB, reduced IκBα, and increased expression of proinflammatory cytokines in vascular endothelial cells of healthy humans , 2008, Aging cell.

[19]  R. Bolli,et al.  Impact of 6-mo caloric restriction on myocardial ischemic tolerance: possible involvement of nitric oxide-dependent increase in nuclear Sirt1. , 2008, American journal of physiology. Heart and circulatory physiology.

[20]  Judith Campisi,et al.  Senescence-Associated Secretory Phenotypes Reveal Cell-Nonautonomous Functions of Oncogenic RAS and the p53 Tumor Suppressor , 2008, PLoS biology.

[21]  Chao-Yung Wang,et al.  Increased Vascular Senescence and Impaired Endothelial Progenitor Cell Function Mediated by Mutation of Circadian Gene Per2 , 2008, Circulation.

[22]  T. Lüscher,et al.  The role of p66Shc deletion in age-associated arterial dysfunction and disease states. , 2008, Journal of applied physiology.

[23]  De-Pei Liu,et al.  Endothelium-specific overexpression of class III deacetylase SIRT1 decreases atherosclerosis in apolipoprotein E-deficient mice. , 2008, Cardiovascular research.

[24]  S. Austad,et al.  Endothelial function and vascular oxidative stress in long‐lived GH/IGF‐deficient Ames dwarf mice , 2008, American journal of physiology. Heart and circulatory physiology.

[25]  E. Lakatta,et al.  Inflammation and endothelial dysfunction during aging: role of NF-kappaB. , 2008, Journal of applied physiology.

[26]  J. Keaney,et al.  Suppression of the JNK Pathway by Induction of a Metabolic Stress Response Prevents Vascular Injury and Dysfunction , 2008, Circulation.

[27]  E. Ravussin,et al.  In Vitro Cellular Adaptations of Indicators of Longevity in Response to Treatment with Serum Collected from Humans on Calorie Restricted Diets , 2008, PloS one.

[28]  T. Houle,et al.  Effects of short-term treadmill exercise training or growth hormone supplementation on diastolic function and exercise tolerance in old rats. , 2008, The journals of gerontology. Series A, Biological sciences and medical sciences.

[29]  T. Rassaf,et al.  Impaired endothelial progenitor cell function predicts age-dependent carotid intimal thickening , 2008, Basic Research in Cardiology.

[30]  Leonid Peshkin,et al.  Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. , 2008, Cell metabolism.

[31]  S. Rohrbach,et al.  Age-specific effects of short- and long-term caloric restriction on the expression of adiponectin and adiponectin receptors: Influence of intensity of food restriction , 2008, Experimental Gerontology.

[32]  S. Beske,et al.  Weight Loss Alone Improves Conduit and Resistance Artery Endothelial Function in Young and Older Overweight/Obese Adults , 2008, Hypertension.

[33]  StefanieDimmeler,et al.  Aging and Disease as Modifiers of Efficacy of Cell Therapy , 2008 .

[34]  Sang Mi Ahn,et al.  Effect of weight loss on some serum cytokines in human obesity: increase in IL-10 after weight loss. , 2008, The Journal of nutritional biochemistry.

[35]  R. de Cabo,et al.  Vasoprotective effects of resveratrol and SIRT1: attenuation of cigarette smoke-induced oxidative stress and proinflammatory phenotypic alterations. , 2008, American journal of physiology. Heart and circulatory physiology.

[36]  Jing Zhang,et al.  Increased Aortic Calpain-1 Activity Mediates Age-Associated Angiotensin II Signaling of Vascular Smooth Muscle Cells , 2008, PloS one.

[37]  S. Austad,et al.  Oxidative stress in vascular senescence: lessons from successfully aging species. , 2008, Frontiers in bioscience : a journal and virtual library.

[38]  Z. Ungvari,et al.  Dysregulation of mitochondrial biogenesis in vascular endothelial and smooth muscle cells of aged rats. , 2008, American journal of physiology. Heart and circulatory physiology.

[39]  P. Nawroth,et al.  Insulin Stimulates the Clonogenic Potential of Angiogenic Endothelial Progenitor Cells by IGF-1 Receptor-Dependent Signaling , 2008, Molecular medicine.

[40]  Jennifer M. A. Tullet,et al.  Direct Inhibition of the Longevity-Promoting Factor SKN-1 by Insulin-like Signaling in C. elegans , 2008, Cell.

[41]  R. de Cabo,et al.  Mechanisms Underlying Caloric Restriction and Lifespan Regulation: Implications for Vascular Aging , 2008, Circulation research.

[42]  C. Bearzi,et al.  Activation of Cardiac Progenitor Cells Reverses the Failing Heart Senescent Phenotype and Prolongs Lifespan , 2008, Circulation research.

[43]  Z. Ungvari,et al.  CB2 cannabinoid receptor stimulation attenuates TNF‐alpha‐induced human endothelial cell activation, transendothelial migration of monocytes, and monocyte‐endothelial adhesion. , 2008 .

[44]  Joy W. Chang,et al.  Nrf2 mediates cancer protection but not prolongevity induced by caloric restriction , 2008, Proceedings of the National Academy of Sciences.

[45]  P. Calder,et al.  Age-related increases in circulating inflammatory markers in men are independent of BMI, blood pressure and blood lipid concentrations. , 2008, Atherosclerosis.

[46]  T. Lüscher,et al.  The role of p 66 Shc deletion in age-associated arterial dysfunction and disease states , 2008 .

[47]  R. Bolli,et al.  Cardioprotective Effects of Short-Term Caloric Restriction Are Mediated by Adiponectin via Activation of AMP-Activated Protein Kinase , 2007, Circulation.

[48]  A. Giaccia,et al.  Age Decreases Endothelial Progenitor Cell Recruitment Through Decreases in Hypoxia-Inducible Factor 1α Stabilization During Ischemia , 2007, Circulation.

[49]  D. Seals,et al.  High-dose ascorbic acid infusion abolishes chronic vasoconstriction and restores resting leg blood flow in healthy older men. , 2007, Journal of applied physiology.

[50]  K. Mackie,et al.  CB2-receptor stimulation attenuates TNF-alpha-induced human endothelial cell activation, transendothelial migration of monocytes, and monocyte-endothelial adhesion. , 2007, American journal of physiology. Heart and circulatory physiology.

[51]  Yuzhi Zhang,et al.  Biomechanical Forces in Atherosclerosis-Resistant Vascular Regions Regulate Endothelial Redox Balance via Phosphoinositol 3-Kinase/Akt-Dependent Activation of Nrf2 , 2007, Circulation research.

[52]  Cuk-Seong Kim,et al.  SIRT1 promotes endothelium-dependent vascular relaxation by activating endothelial nitric oxide synthase , 2007, Proceedings of the National Academy of Sciences.

[53]  Pál Pacher,et al.  Decreased age-related cardiac dysfunction, myocardial nitrative stress, inflammatory gene expression, and apoptosis in mice lacking fatty acid amide hydrolase. , 2007 .

[54]  Andre Fischer,et al.  SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer's disease and amyotrophic lateral sclerosis , 2007, The EMBO journal.

[55]  M. Karck,et al.  Single dose treatment with PARP-inhibitor INO-1001 improves aging-associated cardiac and vascular dysfunction , 2007, Experimental Gerontology.

[56]  Z. Ungvari,et al.  Increased mitochondrial H2O2 production promotes endothelial NF- B activation in aged rat arteries , 2007 .

[57]  R. Virmani,et al.  Proinflammatory Profile Within the Grossly Normal Aged Human Aortic Wall , 2007, Hypertension.

[58]  G. Pierce,et al.  Direct Evidence of Endothelial Oxidative Stress With Aging in Humans: Relation to Impaired Endothelium-Dependent Dilation and Upregulation of Nuclear Factor-&kgr;B , 2007, Circulation research.

[59]  Qun Gao,et al.  Aging enhances pressure-induced arterial superoxide formation. , 2007, American journal of physiology. Heart and circulatory physiology.

[60]  M. Delp,et al.  Exercise training enhances flow-induced vasodilation in skeletal muscle resistance arteries of aged rats: role of PGI2 and nitric oxide. , 2007, American journal of physiology. Heart and circulatory physiology.

[61]  Z. Ungvari,et al.  Resveratrol attenuates TNFalfa‐induced activation of coronary arterial endothelial cells: role of NF‐kB inhibition , 2007 .

[62]  Z. Ungvari,et al.  Resveratrol Increases Vascular Oxidative Stress Resistance , 2007, American journal of physiology. Heart and circulatory physiology.

[63]  Z. Ungvari,et al.  Vascular aging in the longest‐living rodent, the naked mole‐rat , 2007, American journal of physiology. Heart and circulatory physiology.

[64]  Greta L. Hoetzer,et al.  Aging, exercise, and endothelial progenitor cell clonogenic and migratory capacity in men. , 2007, Journal of applied physiology.

[65]  K. Moreau,et al.  Oxidative stress contributes to chronic leg vasoconstriction in estrogen-deficient postmenopausal women. , 2007, Journal of applied physiology.

[66]  Jun Ren,et al.  Cardiac-specific overexpression of insulin-like growth factor 1 attenuates aging-associated cardiac diastolic contractile dysfunction and protein damage. , 2007, American journal of physiology. Heart and circulatory physiology.

[67]  P. Poole‐Wilson,et al.  Age-Dependent Impairment of Endothelial Progenitor Cells Is Corrected by Growth Hormone Mediated Increase of Insulin-Like Growth Factor-1 , 2007, Circulation research.

[68]  J. Groves,et al.  The peroxynitrite decomposition catalyst FP15 improves ageing-associated cardiac and vascular dysfunction , 2007, Mechanisms of Ageing and Development.

[69]  F. Metzger,et al.  Disturbed Cross Talk between Insulin-Like Growth Factor I and AMP-Activated Protein Kinase as a Possible Cause of Vascular Dysfunction in the Amyloid Precursor Protein/Presenilin 2 Mouse Model of Alzheimer's Disease , 2007, The Journal of Neuroscience.

[70]  T. Kodama,et al.  Shear stress stabilizes NF-E2-related factor 2 and induces antioxidant genes in endothelial cells: role of reactive oxygen/nitrogen species. , 2007, Free radical biology & medicine.

[71]  Z. Ungvari,et al.  Vasculoprotective effects of anti-tumor necrosis factor-alpha treatment in aging. , 2007, The American journal of pathology.

[72]  P. Ferdinandy,et al.  Cigarette smoke-induced proinflammatory alterations in the endothelial phenotype: role of NAD(P)H oxidase activation. , 2007, American journal of physiology. Heart and circulatory physiology.

[73]  L. Liaudet,et al.  Nitric oxide and peroxynitrite in health and disease. , 2007, Physiological reviews.

[74]  P. Puigserver,et al.  Resveratrol Improves Mitochondrial Function and Protects against Metabolic Disease by Activating SIRT1 and PGC-1α , 2006, Cell.

[75]  F. Sweep,et al.  Haematopoietic stem cells and endothelial progenitor cells in healthy men: effect of aging and training , 2006, Aging cell.

[76]  P. Puigserver,et al.  Resveratrol improves health and survival of mice on a high-calorie diet , 2006, Nature.

[77]  Z. Ungvari,et al.  Resveratrol attenuates TNF-α-induced activation of coronary arterial endothelial cells: role of NF-κB inhibition , 2006 .

[78]  Y. Dohi,et al.  Temocapril, an Angiotensin Converting Enzyme Inhibitor, Ameliorates Age-Related Increase in Carotid Arterial Stiffness in Normotensive Subjects , 2006, Cardiology.

[79]  P. Vanhoutte,et al.  Endothelial dysfunction: a multifaceted disorder (The Wiggers Award Lecture). , 2006, American journal of physiology. Heart and circulatory physiology.

[80]  E. Ravussin,et al.  Role of adiponectin in human skeletal muscle bioenergetics. , 2006, Cell metabolism.

[81]  Joseph A. Baur,et al.  Therapeutic potential of resveratrol: the in vivo evidence , 2006, Nature Reviews Drug Discovery.

[82]  D. Riddle,et al.  Growth hormone and IGF-I modulate local cerebral glucose utilization and ATP levels in a model of adult-onset growth hormone deficiency. , 2006, American journal of physiology. Endocrinology and metabolism.

[83]  C. Fernandez-Patron,et al.  Vascular Responses to &agr;1-Adrenergic Receptors in Small Rat Mesenteric Arteries Depend on Mitochondrial Reactive Oxygen Species , 2006 .

[84]  D. Seals,et al.  Xanthine oxidase does not contribute to impaired peripheral conduit artery endothelium‐dependent dilatation with ageing , 2006, The Journal of physiology.

[85]  S. Davidge,et al.  Age-associated impairment in vasorelaxation to fluid shear stress in the female vasculature is improved by TNF-alpha antagonism. , 2006, American journal of physiology. Heart and circulatory physiology.

[86]  Hirofumi Tanaka,et al.  Resistance Training Increases Basal Limb Blood Flow and Vascular Conductance in Aging Humans , 2006, Journal of applied physiology.

[87]  H. Chung,et al.  Upregulation of aortic adhesion molecules during aging. , 2006, The journals of gerontology. Series A, Biological sciences and medical sciences.

[88]  Zhen-Yu Chen,et al.  Reactive oxygen species in vascular wall. , 2006, Cardiovascular & hematological disorders drug targets.

[89]  R. de Cabo,et al.  Calorie restriction induces mitochondrial biogenesis and bioenergetic efficiency. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[90]  Pingfang Liu,et al.  Genomic Instability and Aging-like Phenotype in the Absence of Mammalian SIRT6 , 2006, Cell.

[91]  S. Kovacs,et al.  Long-term caloric restriction ameliorates the decline in diastolic function in humans. , 2006, Journal of the American College of Cardiology.

[92]  Z. Ungvari,et al.  Resveratrol attenuates TNF-alpha-induced activation of coronary arterial endothelial cells: role of NF-kappaB inhibition. , 2006, American journal of physiology. Heart and circulatory physiology.

[93]  Z. Ungvari,et al.  Altered mitochondrial energy metabolism may play a role in vascular aging. , 2006, Medical hypotheses.

[94]  D. Kitzman,et al.  Growth hormone replacement attenuates diastolic dysfunction and cardiac angiotensin II expression in senescent rats. , 2006, The journals of gerontology. Series A, Biological sciences and medical sciences.

[95]  T. Yamamori,et al.  P66shc regulates endothelial NO production and endothelium-dependent vasorelaxation: implications for age-associated vascular dysfunction. , 2005, Journal of molecular and cellular cardiology.

[96]  A. Sapino,et al.  Calorie restriction protects against age‐related rat aorta sclerosis , 2005, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[97]  D. Seals,et al.  Tetrahydrobiopterin augments endothelium‐dependent dilatation in sedentary but not in habitually exercising older adults , 2005, The Journal of physiology.

[98]  E. Lakatta,et al.  Angiotensin II activates matrix metalloproteinase type II and mimics age-associated carotid arterial remodeling in young rats. , 2005, The American journal of pathology.

[99]  Emilio Clementi,et al.  Calorie Restriction Promotes Mitochondrial Biogenesis by Inducing the Expression of eNOS , 2005, Science.

[100]  A. Csiszar,et al.  Transcriptional basis for exercise limitation in male eNOS-knockout mice with age: heart failure and the fetal phenotype. , 2005, American journal of physiology. Heart and circulatory physiology.

[101]  Hirofumi Tanaka,et al.  Lack of age-related decreases in basal whole leg blood flow in resistance-trained men. , 2005, Journal of applied physiology.

[102]  D. Torella,et al.  Cardiac Stem Cells Possess Growth Factor-Receptor Systems That After Activation Regenerate the Infarcted Myocardium, Improving Ventricular Function and Long-Term Survival , 2005, Circulation research.

[103]  Edward G Lakatta,et al.  Arterial aging: is it an immutable cardiovascular risk factor? , 2005, Hypertension.

[104]  R. Weindruch,et al.  Long-term caloric restriction increases UCP3 content but decreases proton leak and reactive oxygen species production in rat skeletal muscle mitochondria. , 2005, American journal of physiology. Endocrinology and metabolism.

[105]  R. Loeser,et al.  Adult-onset growth hormone and insulin-like growth factor I deficiency reduces neoplastic disease, modifies age-related pathology, and increases life span. , 2005, Endocrinology.

[106]  S. Davidge,et al.  Chronic Tumor Necrosis Factor-&agr; Inhibition Enhances NO Modulation of Vascular Function in Estrogen-Deficient Rats , 2005, Hypertension.

[107]  M. Adams,et al.  Functional characterization of des-IGF-1 action at excitatory synapses in the CA1 region of rat hippocampus. , 2005, Journal of neurophysiology.

[108]  M. Emond,et al.  Extension of Murine Life Span by Overexpression of Catalase Targeted to Mitochondria , 2005, Science.

[109]  A. Tedgui,et al.  Age and gender effects on apoptosis in the human coronary arterial wall , 2005, Mechanisms of Ageing and Development.

[110]  K. Moreau,et al.  Ascorbic Acid Selectively Improves Large Elastic Artery Compliance in Postmenopausal Women , 2005, Hypertension.

[111]  M. Kelm,et al.  Impaired progenitor cell activity in age-related endothelial dysfunction. , 2005, Journal of the American College of Cardiology.

[112]  C. Carter,et al.  Growth hormone and insulin-like growth factor-1 (IGF-1) and their influence on cognitive aging , 2005, Ageing Research Reviews.

[113]  J. Brunso-Bechtold,et al.  Differential effects of aging and insulin-like growth factor-1 on synapses in CA1 of rat hippocampus. , 2005, Cerebral cortex.

[114]  H. Girouard,et al.  Acute and chronic effects of free radicals on α1-adrenergic-induced vasoconstriction in mesenteric beds of spontaneously hypertensive rats , 2005 .

[115]  D. Seals,et al.  Ascorbic acid does not affect the age-associated reduction in maximal cardiac output and oxygen consumption in healthy adults. , 2005, Journal of applied physiology.

[116]  J. Campisi.  Senescent Cells, Tumor Suppression, and Organismal Aging: Good Citizens, Bad Neighbors , 2005, Cell.

[117]  T. Imanishi,et al.  Angiotensin II accelerates endothelial progenitor cell senescence through induction of oxidative stress , 2005, Journal of hypertension.

[118]  J. Wands,et al.  Insulin and insulin-like growth factor expression and function deteriorate with progression of Alzheimer's disease: link to brain reductions in acetylcholine. , 2005, Journal of Alzheimer's disease : JAD.

[119]  J. Weiner,et al.  Growth hormone treatment attenuates age-related changes in hippocampal short-term plasticity and spatial learning , 2004, Neuroscience.

[120]  A. Bürkle,et al.  Poly(ADP-ribosyl)ation and aging , 2004, Experimental Gerontology.

[121]  C. Szabó,et al.  A New, Potent Poly(ADP-ribose) Polymerase Inhibitor Improves Cardiac and Vascular Dysfunction Associated with Advanced Aging , 2004, Journal of Pharmacology and Experimental Therapeutics.

[122]  P. Holvoet.  Oxidized LDL and coronary heart disease , 2004, Acta cardiologica.

[123]  A. Csiszar,et al.  Premature death and age-related cardiac dysfunction in male eNOS-knockout mice. , 2004, Journal of molecular and cellular cardiology.

[124]  I. Young,et al.  Protective effects of ascorbic acid on arterial hemodynamics during acute hyperglycemia. , 2004, American journal of physiology. Heart and circulatory physiology.

[125]  J. Wood,et al.  Sirtuin activators mimic caloric restriction and delay ageing in metazoans , 2004, Nature.

[126]  A. Onat,et al.  Measures of abdominal obesity assessed for visceral adiposity and relation to coronary risk , 2004, International Journal of Obesity.

[127]  E. Lakatta,et al.  Rat Aortic MCP-1 and Its Receptor CCR2 Increase With Age and Alter Vascular Smooth Muscle Cell Function , 2004, Arteriosclerosis, thrombosis, and vascular biology.

[128]  Myriam Gorospe,et al.  Calorie Restriction Promotes Mammalian Cell Survival by Inducing the SIRT1 Deacetylase , 2004, Science.

[129]  D. Seals,et al.  Ascorbic acid increases cardiovagal baroreflex sensitivity in healthy older men. , 2004, American journal of physiology. Heart and circulatory physiology.

[130]  T. Oury,et al.  Reduced release of nitric oxide to shear stress in mesenteric arteries of aged rats. , 2004, American journal of physiology. Heart and circulatory physiology.

[131]  Matthias Egger,et al.  Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis , 2004, The Lancet.

[132]  Hong Yang,et al.  Food restriction attenuates age-related increase in the sensitivity of endothelial cells to oxidized lipids. , 2004, The journals of gerontology. Series A, Biological sciences and medical sciences.

[133]  D. Seals,et al.  Effect of acute and chronic ascorbic acid on flow‐mediated dilatation with sedentary and physically active human ageing , 2004, The Journal of physiology.

[134]  D. Seals,et al.  Ascorbic acid does not affect large elastic artery compliance or central blood pressure in young and older men. , 2004, American journal of physiology. Heart and circulatory physiology.

[135]  Z. Ungvari,et al.  Proinflammatory phenotype of coronary arteries promotes endothelial apoptosis in aging. , 2004, Physiological genomics.

[136]  T. Hagen,et al.  Decline in transcriptional activity of Nrf2 causes age-related loss of glutathione synthesis, which is reversible with lipoic acid. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[137]  Mark A Sussman,et al.  Cardiac Stem Cell and Myocyte Aging, Heart Failure, and Insulin-Like Growth Factor-1 Overexpression , 2004, Circulation research.

[138]  H. Chung,et al.  Alteration of soluble adhesion molecules during aging and their modulation by calorie restriction , 2004, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[139]  J. Yélamos,et al.  Transcription regulation of TNF-alpha-early response genes by poly(ADP-ribose) polymerase-1 in murine heart endothelial cells. , 2004, Nucleic acids research.

[140]  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.

[141]  T. Lüscher,et al.  Deletion of p66shc Gene Protects Against Age-Related Endothelial Dysfunction , 2003, Circulation.

[142]  A. Shoukas,et al.  Arginase Reciprocally Regulates Nitric Oxide Synthase Activity and Contributes to Endothelial Dysfunction in Aging Blood Vessels , 2003, Circulation.

[143]  R. D'Agostino,et al.  Cytokines, insulin-like growth factor 1, sarcopenia, and mortality in very old community-dwelling men and women: the Framingham Heart Study. , 2003, The American journal of medicine.

[144]  D. Seals,et al.  Oxidative stress does not modulate metabolic rate or skeletal muscle sympathetic activity with primary aging in adult humans. , 2003, The Journal of clinical endocrinology and metabolism.

[145]  T. Hintze,et al.  NAD(P)H oxidase-generated superoxide anion accounts for reduced control of myocardial O2 consumption by NO in old Fischer 344 rats. , 2003, American journal of physiology. Heart and circulatory physiology.

[146]  Z. Ungvari,et al.  Aging‐induced proinflammatory shift in cytokine expression profile in rat coronary arteries , 2003, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[147]  M. Gorospe,et al.  An in vitro model of caloric restriction , 2003, Experimental Gerontology.

[148]  S. Melov,et al.  Oxygen sensitivity severely limits the replicative lifespan of murine fibroblasts , 2003, Nature Cell Biology.

[149]  E. Lakatta,et al.  Aging Increases Aortic MMP‐2 Activity and Angiotensin II in Nonhuman Primates , 2003, Hypertension.

[150]  M. Matsuda,et al.  Exercise training improves ageing-induced decrease in eNOS expression of the aorta. , 2003, Acta physiologica Scandinavica.

[151]  B. Aronow,et al.  Absence of Poly(ADP-ribose) Polymerase-1 Alters Nuclear Factor-κB Activation and Gene Expression of Apoptosis Regulators after Reperfusion Injury , 2003, Molecular medicine.

[152]  David R. Riddle,et al.  Microvascular plasticity in aging , 2003, Ageing Research Reviews.

[153]  J. Sastre,et al.  Mitochondria from females exhibit higher antioxidant gene expression and lower oxidative damage than males. , 2003, Free radical biology & medicine.

[154]  K. Moreau,et al.  Basal leg blood flow in healthy women is related to age and hormone replacement therapy status. , 2003, The Journal of physiology.

[155]  M. O’connor,et al.  Poly(ADP-Ribose) Polymerase-1 Regulates Activation of Activator Protein-1 in Murine Fibroblasts1 , 2003, The Journal of Immunology.

[156]  C. Napoli,et al.  Deletion of the p66Shc longevity gene reduces systemic and tissue oxidative stress, vascular cell apoptosis, and early atherogenesis in mice fed a high-fat diet , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[157]  E. Barrett,et al.  Blood flow and muscle metabolism: a focus on insulin action. , 2003, American journal of physiology. Endocrinology and metabolism.

[158]  C. Kunsch,et al.  Laminar Flow Induction of Antioxidant Response Element-mediated Genes in Endothelial Cells , 2003, The Journal of Biological Chemistry.

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

[160]  T. Hintze,et al.  NAD ( P ) H oxidase-generated superoxide anion accounts for reduced control of myocardial O 2 consumption by NO in old Fischer 344 rats , 2003 .

[161]  I. Young,et al.  Ascorbic Acid Reduces Blood Pressure and Arterial Stiffness in Type 2 Diabetes , 2002, Hypertension.

[162]  B. Fagerberg,et al.  Circulating oxidized low‐density lipoprotein (LDL) is associated with risk factors of the metabolic syndrome and LDL size in clinically healthy 58‐year‐old men (AIR study) , 2002, Journal of internal medicine.

[163]  E. Price,et al.  Aging induces muscle-specific impairment of endothelium-dependent dilation in skeletal muscle feed arteries. , 2002, Journal of applied physiology.

[164]  Z. Ungvari,et al.  Aging-Induced Phenotypic Changes and Oxidative Stress Impair Coronary Arteriolar Function , 2002, Circulation research.

[165]  C. Carter,et al.  A critical analysis of the role of growth hormone and IGF-1 in aging and lifespan. , 2002, Trends in genetics : TIG.

[166]  C. Szabó,et al.  Activation of poly(ADP-ribose) polymerase contributes to the endothelial dysfunction associated with hypertension and aging. , 2002, International journal of molecular medicine.

[167]  K. Moreau,et al.  Changes in maximal aerobic capacity with age in endurance-trained women: 7-yr follow-up. , 2002, Journal of applied physiology.

[168]  S. Prasad,et al.  Ageing is associated with impairment of nitric oxide and prostanoid dilator pathways in the human forearm. , 2002, Clinical science.

[169]  D. Sane,et al.  Growth hormone, insulin-like growth factor-1 and the aging cardiovascular system. , 2002, Cardiovascular research.

[170]  C. Szabó,et al.  Endothelial dysfunction in aging animals: the role of poly(ADP‐ribose) polymerase activation , 2002, British journal of pharmacology.

[171]  A. Takeshita,et al.  Greater Oxidative Stress in Healthy Young Men Compared With Premenopausal Women , 2002, Arteriosclerosis, thrombosis, and vascular biology.

[172]  S. Snyder,et al.  Poly(ADP-ribose) polymerase-1 dependence of stress-induced transcription factors and associated gene expression in glia , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[173]  K. Chayama,et al.  A low-calorie diet improves endothelium-dependent vasodilation in obese patients with essential hypertension. , 2000, American journal of hypertension.

[174]  M. Kurabayashi,et al.  Production of nitric oxide, but not prostacyclin, is reduced in klotho mice. , 2002, Japanese journal of pharmacology.

[175]  S. Bennett,et al.  Intracerebroventricular infusion of insulin-like growth factor-I ameliorates the age-related decline in hippocampal neurogenesis , 2001, Neuroscience.

[176]  D. Riddle,et al.  Effects of age and insulin-like growth factor-1 on neuron and synapse numbers in area CA3 of hippocampus , 2001, Neuroscience.

[177]  Hirofumi Tanaka,et al.  Reductions in basal limb blood flow and vascular conductance with human ageing: role for augmented α‐adrenergic vasoconstriction , 2001, The Journal of physiology.

[178]  P. Tsao,et al.  eNOS Activity Is Reduced in Senescent Human Endothelial Cells: Preservation by hTERT Immortalization , 2001, Circulation research.

[179]  A. Zeiher,et al.  Aging Enhances the Sensitivity of Endothelial Cells Toward Apoptotic Stimuli: Important Role of Nitric Oxide , 2001, Circulation research.

[180]  Hong Yang,et al.  Effects of age and food restriction on oxidative DNA damage and antioxidant enzyme activities in the mouse aorta , 2001, Mechanisms of Ageing and Development.

[181]  D. Kass,et al.  Improved Arterial Compliance by a Novel Advanced Glycation End-Product Crosslink Breaker , 2001, Circulation.

[182]  J. Oxtoby,et al.  Biochemical and biophysical markers of endothelial dysfunction in adults with hypopituitarism and severe GH deficiency. , 2001, The Journal of clinical endocrinology and metabolism.

[183]  L. Ghiadoni,et al.  Age-Related Reduction of NO Availability and Oxidative Stress in Humans , 2001, Hypertension.

[184]  Richard A. Miller,et al.  Lifespan extension and delayed immune and collagen aging in mutant mice with defects in growth hormone production , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[185]  R. Victor,et al.  Impaired Modulation of Sympathetic Vasoconstriction in Contracting Skeletal Muscle of Rats With Chronic Myocardial Infarctions: Role of Oxidative Stress , 2001, Circulation research.

[186]  Y. G. Kim,et al.  Impaired angiogenesis in the aging kidney: vascular endothelial growth factor and thrombospondin-1 in renal disease. , 2001, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[187]  Hirofumi Tanaka,et al.  Age‐related decreases in basal limb blood flow in humans: time course, determinants and habitual exercise effects , 2001, The Journal of physiology.

[188]  J. Keaney,et al.  Effect of ascorbic acid treatment on conduit vessel endothelial dysfunction in patients with hypertension. , 2001, American journal of physiology. Heart and circulatory physiology.

[189]  A. Dominiczak,et al.  Superoxide Excess in Hypertension and Aging: A Common Cause of Endothelial Dysfunction , 2001, Hypertension.

[190]  T. Lüscher,et al.  Enhanced Peroxynitrite Formation Is Associated with Vascular Aging , 2000, The Journal of experimental medicine.

[191]  S. Bennett,et al.  The effects of growth hormone and IGF‐1 deficiency on cerebrovascular and brain ageing , 2000, Journal of anatomy.

[192]  Hirofumi Tanaka,et al.  Regular Aerobic Exercise Prevents and Restores Age-Related Declines in Endothelium-Dependent Vasodilation in Healthy Men , 2000, Circulation.

[193]  S. Kihara,et al.  Adiponectin, an Adipocyte-Derived Plasma Protein, Inhibits Endothelial NF-&kgr;B Signaling Through a cAMP-Dependent Pathway , 2000, Circulation.

[194]  M. Schroll,et al.  Ageing, tumour necrosis factor‐alpha (TNF‐α) and atherosclerosis , 2000, Clinical and experimental immunology.

[195]  M. Cybulsky,et al.  The NF-kappa B signal transduction pathway in aortic endothelial cells is primed for activation in regions predisposed to atherosclerotic lesion formation. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[196]  L. Ghiadoni,et al.  Physical activity prevents age-related impairment in nitric oxide availability in elderly athletes. , 2000, Circulation.

[197]  C. Franceschi,et al.  Inflamm‐aging: An Evolutionary Perspective on Immunosenescence , 2000 .

[198]  F. Natividad,et al.  Peripheral vascular endothelial dysfunction and apoptosis in old monkeys. , 2000, Arteriosclerosis, thrombosis, and vascular biology.

[199]  H. Soininen,et al.  Severity of Cardiovascular Disease, Apolipoprotein E Genotype, and Brain Pathology in Aging and Dementia , 2000, Annals of the New York Academy of Sciences.

[200]  S. Haffner,et al.  Insulin-resistant prediabetic subjects have more atherogenic risk factors than insulin-sensitive prediabetic subjects: implications for preventing coronary heart disease during the prediabetic state. , 2000, Circulation.

[201]  A. Ceriello.  Oxidative stress and glycemic regulation. , 2000, Metabolism: clinical and experimental.

[202]  R. Schwartz,et al.  Local insulin‐like growth factor I expression induces physiologic, then pathologic, cardiac hypertrophy in transgenic mice , 1999, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[203]  D. Seals,et al.  Limb blood flow and vascular conductance are reduced with age in healthy humans: relation to elevations in sympathetic nerve activity and declines in oxygen demand. , 1999, Circulation.

[204]  M. Hottiger,et al.  A Role of Poly (ADP-Ribose) Polymerase in NF- B Transcriptional Activation , 1999 .

[205]  M. de Lorgeril,et al.  Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: final report of the Lyon Diet Heart Study. , 1999, Circulation.

[206]  J. Keaney,et al.  Long-term ascorbic acid administration reverses endothelial vasomotor dysfunction in patients with coronary artery disease. , 1999, Circulation.

[207]  B. Saltin,et al.  Nitric oxide in the regulation of vasomotor tone in human skeletal muscle. , 1999, American journal of physiology. Heart and circulatory physiology.

[208]  P. Anversa,et al.  Insulin-like growth factor-1 attenuates the detrimental impact of nonocclusive coronary artery constriction on the heart. , 1999, Circulation research.

[209]  H. Cohen,et al.  Associations of elevated interleukin-6 and C-reactive protein levels with mortality in the elderly. , 1999, The American journal of medicine.

[210]  P. Anversa,et al.  Overexpression of insulin-like growth factor-1 attenuates the myocyte renin-angiotensin system in transgenic mice. , 1999, Circulation research.

[211]  J. Isner,et al.  Age-dependent impairment of angiogenesis. , 1999, Circulation.

[212]  M. Hottiger,et al.  A role of poly (ADP-ribose) polymerase in NF-kappaB transcriptional activation. , 1999, Biological chemistry.

[213]  R. Hughson,et al.  Effects of acetylcholine and nitric oxide on forearm blood flow at rest and after a single muscle contraction. , 1998, Journal of applied physiology.

[214]  J. Keaney,et al.  Ascorbate prevents the interaction of superoxide and nitric oxide only at very high physiological concentrations. , 1998, Circulation research.

[215]  R. Paffenbarger,et al.  Physical activity and stroke incidence: the Harvard Alumni Health Study. , 1998, Stroke.

[216]  C. Caramelo,et al.  Expression of constitutive and inducible nitric oxide synthases in the vascular wall of young and aging rats. , 1998, Circulation research.

[217]  M Duriez,et al.  Aminoguanidine prevents age-related arterial stiffening and cardiac hypertrophy. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[218]  K. Beck,et al.  Influence of age and gender on cardiac output-VO2 relationships during submaximal cycle ergometry. , 1998, Journal of applied physiology.

[219]  Tadashi Kaname,et al.  Mutation of the mouse klotho gene leads to a syndrome resembling ageing , 1997, Nature.

[220]  Q. Li,et al.  Overexpression of insulin-like growth factor-1 in mice protects from myocyte death after infarction, attenuating ventricular dilation, wall stress, and cardiac hypertrophy. , 1997, The Journal of clinical investigation.

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

[222]  Koutarou D. Kimura,et al.  daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans. , 1997, Science.

[223]  P. Hutchins,et al.  Decreases in cerebral microvasculature with age are associated with the decline in growth hormone and insulin-like growth factor 1. , 1997, Endocrinology.

[224]  D. Le Roith,et al.  Seminars in medicine of the Beth Israel Deaconess Medical Center. Insulin-like growth factors. , 1997 .

[225]  W. Kenney.  Thermoregulation at rest and during exercise in healthy older adults. , 1997, Exercise and sport sciences reviews.

[226]  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.

[227]  Andrzej Bartke,et al.  Dwarf mice and the ageing process , 1996, Nature.

[228]  M. Joyner,et al.  Contribution of nitric oxide and prostaglandins to reactive hyperemia in human forearm. , 1996, Journal of applied physiology.

[229]  P. Anversa,et al.  Necrotic and apoptotic myocyte cell death in the aging heart of Fischer 344 rats. , 1996, The American journal of physiology.

[230]  T. Lüscher,et al.  Effect of age on kinetics of nitric oxide release in rat aorta and pulmonary artery. , 1996, The Journal of clinical investigation.

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

[232]  H. Seto,et al.  Doppler spectral analysis of blood flow velocities in common femoral artery: age-related changes in healthy subjects and characteristics of abnormal hemodynamics in obstructive arterial disease. , 1996, Radiation medicine.

[233]  E. Sonnenblick,et al.  Effects of aging on quantitative structural properties of coronary vasculature and microvasculature in rats. , 1994, The American journal of physiology.

[234]  J. Atkinson,et al.  Effect of chronic ANG I-converting enzyme inhibition on aging processes. III. Endothelial function of mesenteric arterial bed of rat. , 1994, The American journal of physiology.

[235]  J. Michel,et al.  Effect of chronic ANG I-converting enzyme inhibition on aging processes. II. Large arteries. , 1994, The American journal of physiology.

[236]  L. Lind,et al.  Decreased peripheral blood flow in the pathogenesis of the metabolic syndrome comprising hypertension, hyperlipidemia, and hyperinsulinemia. , 1993, American heart journal.

[237]  M. Laakso,et al.  Reduced postprandial skeletal muscle blood flow contributes to glucose intolerance in human obesity. , 1990, The Journal of clinical endocrinology and metabolism.

[238]  S. Austad.  Life extension by dietary restriction in the bowl and doily spider, Frontinella pyramitela , 1989, Experimental Gerontology.

[239]  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.

[240]  T. Lohman,et al.  Anthropometric Standardization Reference Manual , 1988 .

[241]  A Keys,et al.  The diet and 15-year death rate in the seven countries study. , 1986, American journal of epidemiology.

[242]  R. Weindruch,et al.  The retardation of aging in mice by dietary restriction: longevity, cancer, immunity and lifetime energy intake. , 1986, The Journal of nutrition.

[243]  E. Burns,et al.  Changes with age in cerebral capillary morphology , 1981, Neurobiology of Aging.

[244]  E. Burns,et al.  Thinning of capillary walls and declining numbers of endothelial mitochondria in the cerebral cortex of the aging primate, Macaca nemestrina. , 1979, Journal of gerontology.

[245]  W. Montagna,et al.  Structural changes in aging human skin. , 1979, The Journal of investigative dermatology.

[246]  R. Levy,et al.  Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. , 1972, Clinical chemistry.