Functional consequences of impaired autophagy in aging

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Project Title: Functional consequences of impaired autophagy in aging
Principal Investigators (PI): CUERVO ANA M
Project Number: 1P01AG031782-01A1
Organization: ALBERT EINSTEIN COL OF MED YESHIVA UNIV
 
Project Description:
[unreadable] (provided by applicant): This is a new Program Project to investigate the role that age-related changes in autophagy play in the functional alterations and inefficient response to immunological challenges and to stress of old organisms. Four Projects involving 4 faculty members from 3 academic departments are proposed. These projects will share ideas, techniques and experimental models. Completion of most specific aims requires the participation of members from several of the projects. Degradation of intracellular components in lysosomes, or autophagy, is essential for cellular homeostasis, as an energy source when nutrients are sparse and in response to stress. The activity of the two best characterized types of autophagy, macroautophagy and chaperone-mediated autophagy, is altered in old organisms. We hypothesize that this impairment in autophagy could be behind the functional deterioration and the inability to respond to immunological challenges and to stress in old organism. To test this hypothesis we will: 1) characterize the involvement of different autophagic pathways in liver (Project 1 and 4), brain (P1) and the immune system (P2 and 3), under basal or stress conditions; 2) analyze the changes with age in the autophagic system in these organs (P1-4); and 3) determine the contribution of these changes to the metabolic syndrome of aging (P4), the gradual deterioration of cognitive function (P1) and to the failure with age of two essential immune functions, antigen processing and presentation (P2) and T helper cell activation and tolerance (P3). These studies will require the synergistic cooperation of groups with expertise in autophagy, dendritic cell function, T cell biology, steatotic liver disease, lipid metabolism and oxidative cellular injury. This Program includes three Cores: the Administrative Core (Core A) provides the necessary secretarial and bookkeeping functions; the Analytical Imaging Core (Core B) provides state-of-the-art microscopy and imaging services, and the Aging and Transgenic Animal Core (Core C) provides maintenance, breeding and genotyping of the transgenic and aging mouse colonies required for this project. All four Projects are concerned with interrelated areas of cellular metabolism, molecular and cellular immunology and the biology of aging. Each proposed project represents collaborative efforts between independent investigators that will extend their individual expertise into areas that could not otherwise be effectively investigated. The four groups have been working together and will interact synergistically. Significance: These studies may ultimately lead to fundamental insights for understanding, treating or preventing the metabolic alterations and declined cognitive and immune function characteristic of elders. [unreadable] [unreadable] [unreadable]
 
Project Terms:
2PP2A APC ATGN Accounting Acids Address Affect Affinity Age Age Group Unspecified Aged 65 and Over Aging Anatomic Anatomical Sciences Anatomy Animal Model Animal Models and Related Studies Animals Antibodies Antigen Presentation Antigen Presentation Pathway Antigen Processing Antigen Processing and Presentation Antigen Processings Antigen-Presenting Cells Antigens Apoptosis Apoptosis Pathway Applications Grants Appointment Area Articulation Arts Assay Autoimmune Diseases Autophagocytosis Autoregulation Basic Research Basic Science Bioassay Biochemical Biochemistry Biologic Assays Biological Biological Assay Biological Preservation Biology of Aging Blood Coagulation Factor IV Body Tissues Books Brain Breeding CD28 CD28 gene CD4 Positive T Lymphocytes CD4 T cells CD4 lymphocyte CD4+ T cell CD4+ T-Lymphocyte CD4-Positive Lymphocytes Ca++ element Cachectin Cachectin-Tumor Necrosis Factor Calcium Calcium Ion Signaling Calcium Signaling Cancer Biology Cancer, Oncology Cancers Cardiovascular Physiology Cell Aging Cell Communication Cell Communication and Signaling Cell Death Cell Death, Programmed Cell Function Cell Growth in Number Cell Interaction Cell Isolation Cell Multiplication Cell Process Cell Proliferation Cell Segregation Cell Senescence Cell Separation Cell Separation Technology Cell Signaling Cell physiology Cell-to-Cell Interaction Cells Cells, CD4 Cellular Aging Cellular Function Cellular Immunology Cellular Physiology Cellular Process Cellular Proliferation Cellular biology Cellular injury Central Nervous System Cessation of life Change of Life, Female Chaperone Characteristics Chemistry, Biological Class II Antigens Class II Major Histocompatibility Antigens Clinical Clinical Research Clinical Study Clinical, Transplantation, Organ Clonal Expansion Coagulation Factor IV Cognitive Cognitive Disturbance Cognitive Impairment Cognitive decline Cognitive function abnormal Collaborations Commit Communication Compensation Core Facility Core Protein Culture Techniques Cultured Cells DISSEC DNA Molecular Biology Data Data Banks Data Bases Databank, Electronic Databanks Database, Electronic Databases Death Defect Degenerative Diseases, Nervous System Degenerative Neurologic Disorders Degradation Pathway Degradative Pathway Dendritic Cells Deterioration Development Diamond Diet Disadvantaged Discipline Disease Disorder Dissection Disturbance in cognition Down-Regulation Down-Regulation (Physiology) Downregulation Dysfunction Dyslipidemias Educational process of instructing Educational workshop Elderly Elderly, over 65 Encephalon Encephalons Endocytosis Energy-Generating Resources Ensure Environmental Factor Environmental Risk Factor Ethnic and Racial Minorities Experimental Models Experimental Models, Other FLR Factor IV Faculty Failure (biologic function) Fatty Acids Fatty Acids, Nonesterified Fatty Acids, Unsaturated Fatty Liver Fellowship Female Health Figs Figs - dietary Financial compensation Free Fatty Acids Functional disorder Funding Future Gene Targeting Generations Genes Genes, Class II Genes, HLA Class II Genes, MHC Class II Genetic Genotype Goals Grafting Procedure Grant Grant Proposals Grants, Applications Group Meetings HLA-DR Associated Protein II Helper Cells Helper T-Cells Helper-Inducer T-Lymphocyte Hepatic Hepatic Cells Hepatic Disorder Hepatic Parenchymal Cell Hepatocyte Hepatology Histocompatibility Antigens Class II Homeostasis Human Human, General I-A Antigen I2PP2A IGAAD Ia Antigens Ia-Like Antigens Idiopathic Parkinson Disease Image Immune Immune Cell Activation Immune Diseases Immune Disorders Immune Dysfunction Immune Function, Cellular Immune Response Antigens Immune System Diseases Immune System Disorder Immune Tolerance Immune response Immune system Immune-Response-Associated Antigens Immunobiology Immunologic Accessory Cells Immunologic Diseases Immunologic Tolerance Immunological Diseases Immunologist Immunology Immunology (Including BRMP) Immunology (NCI Program) Immunomodulators Immunophysiology Impaired cognition Impairment Individual Inducer Cells Information Technology Inhibitor of GZMA-Activated DNase Injury Injury to Liver Institutes Interest Group Intermediary Metabolism Intracellular Communication and Signaling Intranet Investigation Investigators Joints Journals Knockout Mice Knowledge Laboratories Laboratory Study Lead Length of Life Lentivirinae Lentivirus Letters Lewy Body Parkinson Disease Link Lipids Liver Liver Cells Liver Steatosis Liver diseases Longevity Lysosomes METBL MHC Class II MHC Class II Genes MHC Class II Molecule MHC Class II Protein MHC class II antigen Magazine Maintenance Maintenances Major Histocompatibility Complex Class II Malignant Neoplasms Malignant Tumor Mammalian Cell Mammals, Mice Mammals, Rodents Man (Taxonomy) Man, Modern Massachusetts Measurement Measures Mediating Medicine Meetings, Group Membrane Biology Memory Menopause Mentors Metabolic Metabolic Diseases Metabolic Disorder Metabolic Processes Metabolic syndrome Metabolism Metabolism, Lipids/Lipoproteins/Membrane Constituents Methods Methods and Techniques Methods, Other Mice Mice, Knock-out Mice, Knockout Mice, Transgenic Microbiology Microscopy Minority Minority Groups Modeling Models, Experimental Molecular Molecular Biology Molecular Chaperones Molecular Immunology Molecular and Cellular Biology Monocytes / Macrophages / APC Murine Mus NF-AT proteins NFAT proteins NFATC proteins Nerve Cells Nerve Unit Nervous System, Brain Nervous System, CNS Neural Cell Neuraxis Neurocyte Neurodegenerative Diseases Neurodegenerative Disorders Neurologic Degenerative Conditions Neurologic Diseases, Degenerative Neurology Neurons Neurosciences Nonesterified Fatty Acids Null Mouse Nutrient Nutritional Organ Organ Transplantation Organ Transplants Organ Transplants, Including Bone Marrow for DCT Organism Outcome Oxidative Stress PHAPII Paralysis Agitans Parkinson Parkinson Disease Parkinson's Parkinson's disease Parkinsons disease Pathogenesis Pathology Pathway interactions Pb element Peptide-MHC Peptide-Major Histocompatibility Protein Complex Peptide/MHC Complex Peptides Peripheral Pharmacology Phenotype Phosphatase 2A Inhibitor I2PP2A Physiologic pulse Physiological Homeostasis Physiopathology Play Population Position Positioning Attribute Postdoc Postdoctoral Fellow Predisposition Preparation Preservation, Biologic Preservation, Biological Primary Parkinsonism Principal Investigator Procedures Process Production Programs (PT) Programs [Publication Type] Protein Degradation, Metabolic Protein Degradation, Regulatory Protein Turnover Proteins Proteomics Protocol Protocols documentation Pulse Recruitment Activity Regulation Research Research Associate Research Personnel Research Priority Research Resources Research Training Researchers Resistance Resources Risk Rodent Rodentia Rodentias Role SCHED SET Translocation Inhibitor-2 of Protein Phosphatase-2A Sampling Schedule Schools Science of Anatomy Science of Medicine Science of Microbiology Scientist Secondary to Seminal Senescence Senescence, Cellular Senescence, Replicative Series Services Set protein Signal Transduction Signal Transduction Systems Signaling Staging Strategic Planning Stress Students Subcellular Process Subfamily lentivirinae Surface Susceptibility Syndrome System System, LOINC Axis 4 T-Cell Activation T-Cell Proliferation T-Cells T-Cells, Helper-Inducer T-Lymphocyte T-Lymphocytes, Helper T-Lymphocytes, Inducer T4 Cells T4 Lymphocytes T44 TAF-IBETA TNF (unspecified) TNF Receptor Ligands TNF-alpha Targetings, Gene Teaching Techniques Technology Template Activating Factor I Beta Testing Th-1 Cell Th1 Cells Thesaurismosis Thymus-Dependent Lymphocytes Time Tissues Toxin Training Training Programs Transgenic Animals Transgenic Mice Transgenic Mouse Facility Transgenic Organisms Translating Translatings Translations Transplantation Surgery Triacylglycerol Triglycerides Tumor Necrosis Factor Tumor Necrosis Factor Family Protein Tumor Necrosis Factor-alpha Tumor Necrosis Factors Type 1 Helper Cell Universities Unsaturated Fatty Acids Up-Regulation Up-Regulation (Physiology) Upregulation Vaccine Design Veiled Cells Virus-Lenti Whole Organism Analysis Women's Health Work Workshop accessory cell advanced age age dependent age group age related aged aging brain aging population aminoacid sequence of peptide aminoacid sequence of protein anatomy anergy antigen processing autoimmune disorder autophagy base biological adaptation to stress biological signal transduction body system, allergic/immunologic body system, hepatic cardiovascular function cell biology cell damage cell determination cell injury cell sorting cell type clinical data repository clinical data warehouse cognitive dysfunction cognitive function cognitive loss cognitively impaired college conference cytokine data repository decline in function design designing disability disease/disorder elders energy source environmental risk experience experiment experimental research experimental study extracellular failure fat metabolism fluorescence activated cell sorter fluorescence activated cell sorter device functional decline functional loss gene product genetic manipulation geriatric group cooperation heavy metal Pb heavy metal lead helper T cell hepatic steatosis hepatopathy host response imaging immune function immune system tolerance immune unresponsiveness immunogen immunological paralysis immunoresponse immunosenescence in vivo insight interest laboratory facility language translation late life later life life span lifespan lipid metabolism liver disorder liver metabolism living system macrophage malignancy meetings member menopausal metabolism disorder model organism mouse model multidisciplinary necrocytosis neoplasm/cancer neurodegenerative illness neuronal neuropathology new approaches novel novel approaches novel strategies novel strategy novel therapeutic intervention nuclear factor of activated T-cells, cytoplasmic nuclear factors of activated T-cells older adult older person oncology organ allograft organ graft organ system, allergic/immunologic organ system, hepatic organ xenograft oxidant stress pMHC pathophysiology pathway peptide sequence post-doc post-doctoral preservation prevent preventing professor programs protein aminoacid sequence protein degradation reaction crisis recruit relational database research study resistant response restoration senescence senescent senior citizen social role stress response stress stressor structural biology symposium thymus derived lymphocyte tool transcription factor NF-AT transgenic tumor necrosis factor (unspecified)
Project Title: Functional consequences of impaired autophagy in aging
Principal Investigators (PI): CUERVO ANA M
Project Number: 1P01AG031782-01A1
Organization: ALBERT EINSTEIN COL OF MED YESHIVA UNIV
 
Project Categories:
• Natural Sciences > Experimental techniques > in vitro methods > Computer-aided morphometry
 
Other Information:
Fiscal Year: 2009
Project Start Date: 15 February 2009
Project End Date: 31 January 2014
Administering Institute Or Center: AG
 
Project Funding Information:
Total Funding: $2,017,110
Year Funding Organization Total Funding, $
2009 NATIONAL INSTITUTE ON AGING $2,017,110
Project Title: Functional consequences of impaired autophagy in aging
Principal Investigators (PI): CUERVO ANA M
Project Number: 1P01AG031782-01A1
Organization: ALBERT EINSTEIN COL OF MED YESHIVA UNIV
 
Project_number Title Year FY Total Cost
There are no results for this project in database.
Project Title: Functional consequences of impaired autophagy in aging
Principal Investigators (PI): CUERVO ANA M
Project Number: 1P01AG031782-01A1
Organization: ALBERT EINSTEIN COL OF MED YESHIVA UNIV
 
Project number Project title Organization FY Funding Organization FY Total Cost
1R21AG025355-01PROTEOMIC ANALYSIS OF DECREASED AUTOPHAGY IN AGINGALBERT EINSTEIN COL OF MED YESHIVA UNIV2004NATIONAL INSTITUTE ON AGING
$162,444
3R01AG021904-01S1DECREASED PROTEIN DEGRADATION IN AGINGALBERT EINSTEIN COL OF MED YESHIVA UNIV2004NATIONAL INSTITUTE ON AGING
$18,704
5R01AG021904-02DECREASED PROTEIN DEGRADATION IN AGINGALBERT EINSTEIN COL OF MED YESHIVA UNIV2004NATIONAL INSTITUTE ON AGING
$423,714
5R01AG021904-08DECREASED PROTEIN DEGRADATION IN AGINGALBERT EINSTEIN COL OF MED YESHIVA UNIV2010NATIONAL INSTITUTE ON AGING
$336,897
5P01AG031782-02Functional Consequences of Impaired Autophagy in AgingALBERT EINSTEIN COL OF MED YESHIVA UNIV2010NATIONAL INSTITUTE ON AGING
$2,023,075
3R01AG021904-02S1DECREASED PROTEIN DEGRADATION IN AGINGALBERT EINSTEIN COL OF MED YESHIVA UNIV2005NATIONAL INSTITUTE ON AGING
$19,083
5R01AG021904-03DECREASED PROTEIN DEGRADATION IN AGINGALBERT EINSTEIN COL OF MED YESHIVA UNIV2005NATIONAL INSTITUTE ON AGING
$393,721
5R21AG025355-02PROTEOMIC ANALYSIS OF DECREASED AUTOPHAGY IN AGINGALBERT EINSTEIN COL OF MED YESHIVA UNIV2005NATIONAL INSTITUTE ON AGING
$208,750
5R01AG021904-04DECREASED PROTEIN DEGRADATION IN AGINGALBERT EINSTEIN COL OF MED YESHIVA UNIV2006NATIONAL INSTITUTE ON AGING
$366,921
5R01AG021904-05DECREASED PROTEIN DEGRADATION IN AGINGALBERT EINSTEIN COL OF MED YESHIVA UNIV2007NATIONAL INSTITUTE ON AGING
$356,279
3R01AG021904-05S1DECREASED PROTEIN DEGRADATION IN AGINGALBERT EINSTEIN COL OF MED YESHIVA UNIV2007NATIONAL INSTITUTE ON AGING
$99,600
2R01AG021904-06DECREASED PROTEIN DEGRADATION IN AGINGALBERT EINSTEIN COL OF MED YESHIVA UNIV2008NATIONAL INSTITUTE ON AGING
$340,300
1P01AG031782-01A1Functional Consequences of Impaired Autophagy in AgingALBERT EINSTEIN COL OF MED YESHIVA UNIV2009NATIONAL INSTITUTE ON AGING
$2,017,110
5R01AG021904-07DECREASED PROTEIN DEGRADATION IN AGINGALBERT EINSTEIN COL OF MED YESHIVA UNIV2009NATIONAL INSTITUTE ON AGING
$340,300
5R01AG021904-09DECREASED PROTEIN DEGRADATION IN AGINGALBERT EINSTEIN COL OF MED YESHIVA UNIV2011NATIONAL INSTITUTE ON AGING
$303,207
5P01AG031782-03Functional Consequences of Impaired Autophagy in AgingALBERT EINSTEIN COL OF MED YESHIVA UNIV2011NATIONAL INSTITUTE ON AGING
$1,875,398
Project Title: Functional consequences of impaired autophagy in aging
Principal Investigators (PI): CUERVO ANA M
Project Number: 1P01AG031782-01A1
Organization: ALBERT EINSTEIN COL OF MED YESHIVA UNIV
 
Project number Project title Principal investigator
There are no any related projects.
Project Title: Functional consequences of impaired autophagy in aging
Principal Investigators (PI): CUERVO ANA M
Project Number: 1P01AG031782-01A1
Organization: ALBERT EINSTEIN COL OF MED YESHIVA UNIV
 
Title Abstract Authors Year Rel
Methods to monitor chaperone-mediated autophagy. Methods in enzymology. 2009 452 () :297-324 Kaushik, Susmita; Cuervo, Ana Maria 2009
Pioglitazone: more than just an insulin sensitizer. Hepatology (Baltimore, Md.). 2009 May 49 (5) :1427-30 Czaja, Mark J 2009
XBP-1 deficiency in the nervous system protects against amyotrophic lateral sclerosis by increasing autophagy. Genes & development. 2009 Oct 1 23 (19) :2294-306 Hetz, Claudio; Thielen, Peter; Matus, Soledad; Nassif, Melissa; Court, Felipe; Kiffin, Roberta; Martinez, Gabriela; Cuervo, Ana Maria; Brown, Robert H; Glimcher, Laurie H 2009
Autophagy regulates adipose mass and differentiation in mice. The Journal of clinical investigation. 2009 Nov 119 (11) :3329-39 Singh, Rajat; Xiang, Youqing; Wang, Yongjun; Baikati, Kiran; Cuervo, Ana Maria; Luu, Yen K; Tang, Yan; Pessin, Jeffrey E; Schwartz, Gary J; Czaja, Mark J 2009
IKK phosphorylates Huntingtin and targets it for degradation by the proteasome and lysosome. The Journal of cell biology. 2009 Dec 28 187 (7) :1083-99 Thompson, Leslie Michels; Aiken, Charity T; Kaltenbach, Linda S; Agrawal, Namita; Illes, Katalin; Khoshnan, Ali; Martinez-Vincente, Marta; Arrasate, Montserrat; O'Rourke, Jacqueline Gire; Khashwji, Hasan; Lukacsovich, Tamas; Zhu, Ya-Zhen; Lau, Alice L; Massey, Ashish; Hayden, Michael R; Zeitlin, Scott O; Finkbeiner, Steven; Green, Kim N; LaFerla, Frank M; Bates, Gillian; Huang, Lan; Patterson, Paul H; Lo, Donald C; Cuervo, Ana Maria; Marsh, J Lawrence; Steffan, Joan S 2009
Tau fragmentation, aggregation and clearance: the dual role of lysosomal processing. Human molecular genetics. 2009 Nov 1 18 (21) :4153-70 Wang, Yipeng; Martinez-Vicente, Marta; Kruger, Ulrike; Kaushik, Susmita; Wong, Esther; Mandelkow, Eva-Maria; Cuervo, Ana Maria; Mandelkow, Eckhard 2009