Longevity and Stress Resistance

长寿和抗压能力

基本信息

批准号：
7186117
负责人：
STEPHEN F VATNER
金额：
$ 182.23万
依托单位：
UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-06-01 至 2012-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7186117
关键词：
Address Adenovirus Vector Adenoviruses Adenylate Cyclase Adolescent Adverse effects Advisory Committees Affect Age Age Factors Age-Months Aging Aging-Related Process Allegra Animal Disease Models Animal Housing Animal Model Animals Antioxidants Apoptosis Apoptotic Applications Grants Appointment Arts Back Biochemical Biochemistry Bioinformatics Biological Biometry Blood Circulation Bone Development Boxing Breeding Brothers Calcium Caloric Restriction Carbon Dioxide Cardiac Cardiac Myocytes Cardiology Cardiomyopathies Cardiovascular Diseases Cardiovascular Physiology Cardiovascular system Catecholamines Cell Separation Cell Size Cell Survival Cell physiology Cells Cellular biology Centrifugation Chicago Chronic Class Collaborations Collagen Color Commit Communities Complex Computational Technique Computer Systems Computer software Computers Critiques Cyclic AMP-Dependent Protein Kinases DNA Data Data Analyses Databases Deacetylation Dentistry Depth Discipline Disease model Disruption Doctor of Medicine Doctor of Philosophy Dry Ice Electronics End Point Engineering Ensure Environment Enzymes Equipment Exhibits Family Family suidae Feedback Fluorescent Probes Fostering Functional disorder Funding Gamma counter Gene Silencing Genes Genetic Genetic Crosses Genetically Engineered Mouse Genome Genomics Genotype Goals Grant Heart Histone Deacetylase Histopathology Homologous Gene Hormones Human Hypertrophy Ice Illinois Image Image Analysis Immunity In Vitro Incubators Individual Inflammation Institutes Institution Insulin Receptor Insulin-Like Growth Factor I Interdisciplinary Study Internal Medicine Internet Intervention Ischemia Joints Journals Kidney Kidney Diseases Knock-out Knockout Mice Laboratories Laboratory Animal Production and Facilities Lasers Leadership Lesion Letters Life Link Liquid substance Liver Longevity Lower Organism MEKs Magnetic Resonance Imaging Malignant Neoplasms Mammals Manganese Superoxide Dismutase Mass Spectrum Analysis Measurement Mediating Medical Medicine Mentors Metabolic Metabolic Pathway Metabolism Microbiology Microscope Mission Mitochondria Mitogen-Activated Protein Kinases Modeling Molecular Molecular Biology Molecular Genetics Molecular Medicine Mus Myocardial Myocardial Ischemia Myocardium Names Natural History Neoplasms New Jersey Nitrogen Numbers Operating Rooms Operative Surgical Procedures Oranges Organism Osteoporosis Oxidative Stress Participant Pathologic Pathology Pathway interactions Pharmacology Phenotype Physiological Physiological reperfusion Physiology Play Polymerase Chain Reaction Preparation Primates Principal Investigator Process Production Program Research Project Grants Protein Isoforms Protein Overexpression Proteomics Psychiatry Public Health Publications Quarantine Rapid Access to Intervention Development Rate Reactive Oxygen Species Recording of previous events Recovery Room Reperfusion Therapy Reporting Research Research Institute Research Personnel Resistance Resolution Resource Sharing Resources Role Role playing therapy Safety Science Signal Pathway Signal Transduction Site Slide Somatotropin Spleen Stainless Steel Stimulus Stress Study Section Superoxide Dismutase Support of Research Sus scrofa System Techniques Technology Telefacsimile Telephone Temperature Testing Thymus Gland Training Transcriptional Activation Transgenic Mice Transgenic Organisms United States National Institutes of Health Universities Veterinarians Walking Water Water Purification Women&apos s Health Wood material Work Yeasts adenylyl cyclase type V age effect aging population animal care anti aging anticancer research base beta counter bone catalase comparative computerized data space dietary restriction digital disability experience fluorescence microscope fly foot hemodynamics human PEN-2 protein human SOD2 protein ileum in vivo insight insulin signaling interest laboratory facility medical schools member mouse model multidisciplinary muscle metabolism novel pediatric department posters pressure prevent professor programs protective effect repaired response senescence skills statistics success symposium tissue/cell culture tumor yeast genetics young adult

项目摘要

DESCRIPTION (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.

描述（由申请人提供）：该项目的总体主题是检验以下假设：寿命延长，寿命和压力抵抗力是由共同机制介导的。越来越多的证据表明，从酵母到蠕虫，果蝇再到哺乳动物的各种生物的寿命受定义的分子机制调节，包括SIR2，NAD依赖性组蛋白脱乙酰基酶和腺苷酸环化酶蛋白酶酶A酶A途径。理解负责导致衰老的不利影响的关键调节机制的主要局限性，或者相反，那些延长寿命的不良影响是缺乏表现出延长寿命并且不发展心肌病或骨质疏松或其他端点的动物模型，这些模型正常观察到衰老。该模型是最适合增加酵母到灵长类动物的寿命的最佳选择的模型，这是热量限制。提供相对较少的寿命型号。在这方面，我们最近确定了一种新型的基因工程动物模型，该模型的寿命比野生型动物更长，并且没有表现出许多老年的心脏和骨质疏松性特征，即带有腺苷酸环化酶（AC）5“敲除”（ACS KO）的小鼠（AC）。我们的论点是，检查ACS KO模型独有的机制将为衰老过程提供重要的见解，并可能利用可能用于扭转这一过程的机制。项目1和2在此鼠标模型中检查了这些机制。此外，项目3已开发并将研究与sir2alpha相关的其他小鼠衰老和压力抗性的模型。该项目的中心假设是sir2alpha介导了体内心脏中心的抗衰老和细胞保护作用。这三个项目得到了5个核心的支持：行政/生理学；动物护理；基因组学/蛋白质组学；生物信息学/生物统计学；病理。该计划项目对公共卫生有重大影响。与衰老相关的残疾对公共卫生和美国经济产生了重大影响。查找分子开关（例如本项目中描述的开关）可能会随着衰老而改善残疾，这将是前进的主要一步。