Longevity and stress resistance

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Project Title: Longevity and stress resistance
Principal Investigators (PI): VATNER STEPHEN F
Project Number: 5P01AG027211-03
Organization: UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL
 
Project Description:
[unreadable] (provided by applicant): The overall theme of this project is to test the hypothesis that life span extension, longevity and stress resistance are mediated by common mechanisms. Growing lines of evidence suggest that the longevity of a wide variety of organisms, from yeast to worms and flies to mammals, is regulated by defined molecular mechanisms, including Sir2, an NAD-dependent histone deacetylase, and the adenylyl cyclase-protein kinase A pathway. A major limitation to understanding the key regulatory mechanisms responsible for causing the adverse effects of aging, or conversely, those that extend longevity, is the lack of animal models which exhibit prolonged lifespan and which do not develop cardiomyopathy or osteoporosis or other end- points, which are normally observed with aging. The model, which is accepted best for increasing longevity from yeast to primates, is caloric restriction. Relatively few other models for longevity are available. In this connection, we have recently identified a novel, genetically engineered animal model, which lives longer than wild type animals and does not exhibit many of the cardiac and osteoporotic features of old age, i.e., mice with the adenylyl cyclase (AC) type 5 "knocked out" (ACS KO). It is our contention that examining mechanisms that are unique to the ACS KO model will provide important insight into the aging process and, potentially, mechanisms which might be utilized to reverse this process. Projects 1 and 2 examine these mechanisms in this mouse model. In addition, Project 3 has developed and will study other mouse models of aging and stress resistance, related to Sir2alpha. The central hypothesis in that project is that Sir2alpha mediates anti-aging as well as cell protective effects in the heart in vivo. These 3 projects are supported by 5 cores: Administration/Physiology; Animal Care; Genomics/Proteomics; Bioinformatics/Biostatistics; Pathology. This Program Project has major implications for public health. The disability associated with aging has a major impact on the public health and the U.S. economy. Finding molecular switches, such as the ones described in this project, could ameliorate disability with aging and would be a major step forward. [unreadable] [unreadable] [unreadable]
 
Project Terms:
3,5 cyclic AMP synthetase AC5 enzyme ATP pyrophosphate-lyase (cyclizing) Active Oxygen Address Adenosine Cyclic Monophosphate-Dependent Protein Kinases Adenoviral Vector Adenoviridae Adenovirus Vector Adenoviruses Adenyl Cyclase Adenylate Cyclase Adenylyl Cyclase Adverse effects Affect Age Age Factors Age-Months Aged 65 and Over Aging Aging Process Aging-Related Process Analysis, Data Animal Model Animal Models and Related Studies Animals Antioxidants Apoplexy Apoptosis Apoptosis Pathway Apoptotic BP control Binding Proteins Bio-Informatics Biochemical Bioinformatics Biometrics Biometry Biometry and Biostatistics Biostatistics Blood Pressure, High Bone Bone Development Bone and Bones Bones and Bone Tissue Breeding Caloric Restriction Cardiac Cardiac Myocytes Cardiac infarction Cardiocyte Cardiomyopathies Cardiovascular Diseases Catecholamines Cause of Death Cell Communication and Signaling Cell Death, Programmed Cell Function Cell Process Cell Signaling Cell Size Cell Survival Cell Viability Cell physiology Cells Cellular Function Cellular Physiology Cellular Process Cerebral Stroke Cerebrovascular Apoplexy Cerebrovascular Stroke Cerebrovascular accident Cessation of life Chemotherapy-Hormones/Steroids Chicago Chronic Collaborations Collagen Complex Computational Technique Coronary Arteriosclerosis Coronary Artery Disease Coronary Artery Disorder Coronary Atherosclerosis Cyclic AMP-Dependent Protein Kinases Data Data Analyses Deacetylation Death Diapause Discipline Disease Disorder EC 2.7.2- Elderly Elderly, over 65 Endocrine Gland Secretion Endomycetales Engineering Engineerings Enzymes Erythrocuprein Exhibits Extracellular Signal-Regulated Kinases Family Fats Fatty acid glycerol esters Flies GHN Gene Inactivation Gene Silencing GeneHomolog Genome Genomics Genotype Goals Growth Hormone Growth Hormone 1 Growth Hormone Receptor HDAC HDAC Proteins HTRPY Heart Heart failure Heart myocyte Hemocuprein Histone Deacetylase Histopathology Homolog Homologous Gene Homologue Hormones Human Human, General Hydrogen-peroxide[{..}]hydrogen-peroxide oxidoreductase Hypertension Hypertrophy IGF-1 IGF-1 Receptor IGF-I IGF-I-SmC IGF1 IGF1R INSR Illinois In Vitro Insulin Receptor Insulin Receptor Protein-Tyrosine Kinase Insulin-Dependent Tyrosine Protein Kinase Insulin-Like Growth Factor 1 Insulin-Like Growth Factor 1 Receptor Insulin-Like Growth Factor I Insulin-Like Somatomedin Peptide I Insulin-Like-Growth Factor I Receptor Interdisciplinary Research Interdisciplinary Study Intermediary Metabolism Intracellular Communication and Signaling Investigators Ischemia Ischemic Heart Ischemic Heart Disease Ischemic myocardium Isoforms Kidney Knock-out Knockout Knockout Mice Laboratories Length of Life Lesion Life Ligand Binding Protein Liver Longevity Lower Organism MAP kinase MAP-ERK Kinase MAPK MAPK ERK Kinases MEKs METBL MR Imaging MR Tomography MRI Magnetic Resonance Imaging Magnetic Resonance Imaging Scan Mammalia Mammals Mammals, General Mammals, Mice Mammals, Primates Man (Taxonomy) Man, Modern Manganese Superoxide Dismutase Mass Spectrum Mass Spectrum Analysis Measurement Mediating Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance Metabolic Metabolic Pathway Metabolic Processes Metabolism Metabolism, Lipids/Lipoproteins/Membrane Constituents Methods and Techniques Methods, Other Mice Mice, Knock-out Mice, Knockout Mice, Transgenic Mitochondria Mitogen-Activated Protein Kinases Mn Superoxide Dismutase Mn-SOD Modeling Molecular Morbidity Morbidity - disease rate Mortality Mortality Vital Statistics Multidisciplinary Collaboration Multidisciplinary Research Murine Mus Muscle Cells, Cardiac Muscle Cells, Heart Muscle, Cardiac Muscle, Heart Mycocardium Disease Myocardial Myocardial Diseases Myocardial Disorder Myocardial Infarct Myocardial Infarction Myocardial Ischemia Myocardiopathies Myocardium Myocytes, Cardiac NIH NMR Imaging NMR Tomography National Institutes of Health National Institutes of Health (U.S.) Natural History Nematoda Nematodes Neoplasms Nuclear Magnetic Resonance Imaging Null Mouse Operation Operative Procedures Operative Surgical Procedures Organism Osteoporosis Oxidative Stress Oxygen Radicals PKA Pathologic Pathology Pathway interactions Phenotype Photometry/Spectrum Analysis, Mass Physiologic Physiological Physiology Pituitary Growth Hormone Play Pressure Pressure- physical agent Primates Pro-Oxidants Process Production Programs (PT) Programs [Publication Type] Protein Isoforms Protein Kinase A Proteomics Public Health Reactive Oxygen Species Receptor, IGF Type 1 Receptor, IGF-I Receptor, Insulin-Like Growth Factor Type 1 Receptors, Somatotropin Regulatory Protein Reperfusion Therapy Reproduction spores Research Personnel Research Resources Researchers Resistance Resources Reticuloendothelial System, Spleen Reticuloendothelial System, Thymus Risk Factors Role SOD STH Saccharomycetales Science of Statistics Senescence Signal Pathway Signal Transduction Signal Transduction Systems Signaling Somatomedin C Somatotropin Somatotropin Receptor Spectrometry, Mass Spectroscopy, Mass Spectrum Analyses, Mass Spectrum Analysis, Mass Spleen Spores Statistics Stimulus Stress Stroke Study, Interdisciplinary Subcellular Process Superoxide Dismutase Superoxide[{..}]superoxide oxidoreductase Surgical Surgical Interventions Surgical Procedure Sympathins Techniques Testing Therapeutic Hormone Thymus Thymus Gland Thymus Proper Transcription Activation Transcriptional Activation Transgenic Mice Treatment Side Effects Tumors United States National Institutes of Health Universities Up-Regulation Up-Regulation (Physiology) Upregulation Urinary System, Kidney Vascular Accident, Brain Vascular Hypertensive Disease Vascular Hypertensive Disorder Work Yeast, Budding Yeasts Zeugmatography adeno vector adenovector adenylcyclase adenylyl cyclase type 5 adenylyl cyclase type V advanced age age dependent age effect age related aging effect animal care anti aging anti aging drug anti aging medicine anti-oxidant antiaging antiaging drug antiaging medicine biological signal transduction blood pressure control blood pressure homeostasis blood pressure regulation body system, hepatic bone brain attack cAMP-Dependent Protein Kinases calorie restriction cardiac failure cardiac infarct cardiac muscle cardiomyocyte cardiovascular disorder catalase cerebral vascular accident coronary attack coronary infarct coronary infarction cytocuprein diet restriction dietary restriction disability disease/disorder elders fat metabolism fly genetic regulatory protein geriatric hGHN heart attack heart infarct heart infarction heart ischemia heart muscle hemodynamics hyperpiesia hyperpiesis hypertensive disease ileum in vivo insight insulin signaling late life later life life span lifespan lipid metabolism living system member mitochondrial mitochondrial dysfunction model organism mouse model muscle metabolism myocardial ischemia/hypoxia myocardium disorder myocardium ischemia neoplasia neoplastic growth novel older adult older person organ system, hepatic overexpression oxidative damage pathway premature pressure prevent preventing programs protective effect public health medicine (field) receptor binding regulatory gene product renal repair repaired reperfusion resistant response restricted diet roundworm senescence senescent senior citizen side effect skills social role somatotropic hormone statistics statistics/biometry stroke surgery therapy adverse effect treatment adverse effect tumor yeast genetics
Project Title: Longevity and stress resistance
Principal Investigators (PI): VATNER STEPHEN F
Project Number: 5P01AG027211-03
Organization: UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL
 
Project Categories:
• Natural Sciences > Model organisms > Multicellular > Worm
 
Other Information:
Fiscal Year: 2007
Project Start Date: 1 June 2007
Project End Date: 30 April 2012
Administering Institute Or Center: AG
 
Project Funding Information:
Total Funding: $2,182,671
Year Funding Organization Total Funding, $
2009 NATIONAL INSTITUTE ON AGING $2,182,671
Project Title: Longevity and stress resistance
Principal Investigators (PI): VATNER STEPHEN F
Project Number: 5P01AG027211-03
Organization: UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL
 
Project_number Title Year FY Total Cost
There are no results for this project in database.
Project Title: Longevity and stress resistance
Principal Investigators (PI): VATNER STEPHEN F
Project Number: 5P01AG027211-03
Organization: UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL
 
Project number Project title Organization FY Funding Organization FY Total Cost
1P01AG027211-01A1Longevity and Stress ResistanceUNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL2007NATIONAL INSTITUTE ON AGING
$1,822,342
5R01AG014121-11Aging Effects on Cardiovascular FunctionUNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL2007NATIONAL INSTITUTE ON AGING
$563,924
3P01AG027211-02S1Longevity and Stress ResistanceUNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL2008NATIONAL INSTITUTE ON AGING
$166,920
5P01AG027211-02Longevity and Stress ResistanceUNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL2008NATIONAL INSTITUTE ON AGING
$1,948,717
5P01AG027211-03Longevity and Stress ResistanceUNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL2009NATIONAL INSTITUTE ON AGING
$2,182,671
Project Title: Longevity and stress resistance
Principal Investigators (PI): VATNER STEPHEN F
Project Number: 5P01AG027211-03
Organization: UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL
 
Project number Project title Principal investigator
There are no any related projects.
Project Title: Longevity and stress resistance
Principal Investigators (PI): VATNER STEPHEN F
Project Number: 5P01AG027211-03
Organization: UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL
 
Title Abstract Authors Year Rel
Adenylyl cyclase type 5 disruption prolongs longevity and protects the heart against stress. Circulation journal : official journal of the Japanese Circulation Society. 2009 Feb 73 (2) :195-200 Vatner, Stephen F; Yan, Lin; Ishikawa, Yoshihiro; Vatner, Dorothy E; Sadoshima, Junichi 2009
Apoptosis predominates in nonmyocytes in heart failure. American journal of physiology. Heart and circulatory physiology. 2009 Aug 297 (2) :H785-91 Park, Misun; Shen, You-Tang; Gaussin, Vinciane; Heyndrickx, Guy R; Bartunek, Jozef; Resuello, Ranillo R G; Natividad, Filipinas F; Kitsis, Richard N; Vatner, Dorothy E; Vatner, Stephen F 2009
Nicotinamide phosphoribosyltransferase regulates cell survival through NAD+ synthesis in cardiac myocytes. Circulation research. 2009 Aug 28 105 (5) :481-91 Hsu, Chiao-Po; Oka, Shinichi; Shao, Dan; Hariharan, Nirmala; Sadoshima, Junichi 2009
Optimizing cell-based therapy for cardiac regeneration. Circulation. 2009 Sep 8 120 (10) :831-4 Del Re, Dominic P; Sadoshima, Junichi 2009
Genetic inhibition of calcineurin induces diastolic dysfunction in mice with chronic pressure overload. American journal of physiology. Heart and circulatory physiology. 2009 Nov 297 (5) :H1814-9 Gelpi, Ricardo J; Gao, Shumin; Zhai, Peiyong; Yan, Lin; Hong, Chull; Danridge, Lauren M A; Ge, Hui; Maejima, Yasahiro; Donato, Martin; Yokota, Mitsuhiro; Molkentin, Jeffery D; Vatner, Dorothy E; Vatner, Stephen F; Sadoshima, Junichi 2009
Distinct roles of glycogen synthase kinase (GSK)-3alpha and GSK-3beta in mediating cardiomyocyte differentiation in murine bone marrow-derived mesenchymal stem cells. The Journal of biological chemistry. 2009 Dec 25 284 (52) :36647-58 Cho, Jaeyeaon; Rameshwar, Pranela; Sadoshima, Junichi 2009
Cytochrome c oxidase III as a mechanism for apoptosis in heart failure following myocardial infarction. American journal of physiology. Cell physiology. 2009 Oct 297 (4) :C928-34 Wu, Changgong; Yan, Lin; Depre, Christophe; Dhar, Sunil K; Shen, You-Tang; Sadoshima, Junichi; Vatner, Stephen F; Vatner, Dorothy E 2009
Nicotinamide phosphoribosyltransferase regulates cell survival through autophagy in cardiomyocytes. Autophagy. 2009 Nov 5 (8) :1229-31 Hsu, Chiao-Po; Hariharan, Nirmala; Alcendor, Ralph R; Oka, Shinichi; Sadoshima, Junichi 2009