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Principal Investigator: STEPHEN B. KRITCHEVSKY
Organization: MAYO CLINIC ROCHESTER
Fiscal Year: 2024
Award: $744,685
Funding agency: National Institute on Aging
PROJECT SUMMARY/ABSTRACT
Fundamental aging processes appear to be root-cause contributors to most of the disorders and diseases across
the lifespan that account for the bulk of disability, mortality, and health costs. The goal of the nation-wide
Translational Geroscience Network (TGN) is to accelerate translation of geroscience-guided lifestyle, nutritional,
and drug interventions that target these aging processes from biological discovery and pre-clinical validation to
testing in humans. The TGN is motivated by the hypothesis that clinical interventions targeting fundamental
mechanisms of aging can delay, prevent, alleviate, or treat age-related diseases and disabilities as a group,
instead of one at a time (the Geroscience Hypothesis). During the next grant period, the aims of TGN are:
Aim 1) Accelerate development of a diverse portfolio of interventions targeting fundamental aging processes
(gerotherapeutic interventions) by leveraging TGN expertise and infrastructure in terms of study design, outcome
measures selection, quality control, regulatory compliance, biostatistics, data management, gerodiagnostic
assays, and biobanking for translational early phase gerotherapeutic clinical studies. The current 81 endorsed
or planned studies linked to the TGN now include lifestyle and nutritional interventions, metformin, rapalogs, anti-
inflammatories, MitoQ, senolytics, &/or NAD precursors for several indications as well as observational studies.
Aim 2) Discover, develop, select, optimize, and validate gerodiagnostic measures of aging mechanisms across
studies and optimize reference analytical capabilities of the Facilities for Geroscience
Analysis (FGA). The >150 gerodiagnostics and indicators of organ & immune dysfunction that are or will be
tested in response to interventions include analytes in blood, urine, saliva, synovial fluid, buccal swabs, CSF,
biopsies, & other samples from TGN clinical studies.
Aim 3) Provide statistical and data management support to select efficient designs, facilitate sample size
estimates, and incorporate FDA-compliant network-wide data capture, allowing cross-study comparisons.
Sensitive, specific, and reliable phenotypic signatures responsive to interventions that are based on body fluid
analytes, questionnaires, exam findings, physical & cognitive function, imaging, and biopsies will be refined and
composite scores/ signatures integrating these analytes, clinical scales, and physical function tests developed.
Aim 4) Expand TGN biobanking of samples from across studies to facilitate reverse translation, exploratory
analyses, and new ancillary research as hypotheses develop and assays become available. We will continue to
work with the NIA Biobank to ensure sample storage and distribution, even beyond the terms of this award.
Blood (plasma, serum, PBMCs), urine, buccal swabs (& as available, CSF, saliva, biopsies, aqueous humor,
synovial fluid, hair & nail clippings, microbiome), ECG, imaging, medical record (diagnoses, history, physical
signs, routine labs), and questionnaires from TGN/FGA minimally invasive & interventional studies are archived.
The TGN has enormous potential to impact public health through delaying, preventing, alleviating, and treating
multiple disorders and promoting healthspan, the period of life free of disability.
Terms: <0-11 years old><21+ years old><AIDS Virus><Acceleration><Acquired Immune Deficiency Syndrome Virus><Acquired Immunodeficiency Syndrome Virus><Adult><Adult Human><Adult-Onset Diabetes Mellitus><Anti-Inflammatories><Anti-Inflammatory Agents><Anti-inflammatory><Aqueous Humor><Archives><Assay><Award><Bioassay><Biological Assay><Biological Function><Biological Process><Biometrics><Biometry><Biopsy><Biostatistics><Blood><Blood Plasma><Blood Poisoning><Blood Reticuloendothelial System><Blood Serum><Body Fluids><Breast Cancer><COVID-19 long hauler><Cancer Hospital><Cancer Survivor><Cancers><Carpal Tunnel Compression Neuropathy><Carpal Tunnel Entrapment Neuropathy><Carpal Tunnel Median Neuropathy><Carpal Tunnel Syndrome><Child><Child Youth><Children (0-21)><Chronic><Clinic><Clinical><Clinical Research><Clinical Study><Clip><Colorado><Connecticut><Data><Delirium><Development><Diagnosis><Dietary Intervention><Dimethylbiguanidine><Dimethylguanylguanidine><Disease><Disorder><Down's Syndrome><Drugs><ECG><EKG><Education><Educational aspects><Electrocardiogram><Electrocardiography><Enrollment><Ensure><Extended Care Facilities><Funding><Future><Geroscience><Glioblastoma><Goals><Grade IV Astrocytic Neoplasm><Grade IV Astrocytic Tumor><Grade IV Astrocytoma><Grafting Procedure><Grant><HIV><Hair><Health><Health Care Costs><Health Costs><Healthcare Costs><History><Human><Human Immunodeficiency Viruses><Image><Immune Diseases><Immune Disorders><Immune Dysfunction><Immune System Diseases><Immune System Disorder><Immune System Dysfunction><Immune System and Related Disorders><Immunodeficiency and Immunosuppression Disorders><Immunologic Diseases><Immunological Diseases><Immunological Dysfunction><Immunological System Dysfunction><Infrastructure><Institution><Insulin Resistance><Intervention><Intervention Strategies><Intervention Studies><Intraocular Fluid><Investigators><Ketosis-Resistant Diabetes Mellitus><LAV-HTLV-III><Langdon Down syndrome><Life><Life Style><Lifestyle><Link><Lymphadenopathy-Associated Virus><Macular degeneration><Macular degenerative disease><Malignant Breast Neoplasm><Malignant Neoplasms><Malignant Tumor><Maturity-Onset Diabetes Mellitus><Measures><Medical Records><Medication><Metformin><Methods><Michigan><Minnesota><Modern Man><Mongolism><Multiple Myeloma><N,N-dimethyl-imidodicarbonimidic diamide><NIDDM><Nail plate><Nails><Non-Insulin Dependent Diabetes><Non-Insulin-Dependent Diabetes Mellitus><Noninsulin Dependent Diabetes><Noninsulin Dependent Diabetes Mellitus><Nutrition Interventions><Nutritional><Nutritional Interventions><Observation research><Observation study><Observational Study><Observational research><Organ><Organ Transplantation><Organ Transplants><Orthopedic><Orthopedic Surgical Profession><Orthopedics><Outcome Measure><PBMC><Peripheral Blood Mononuclear Cell><Personalized medical approach><Pharmaceutical Preparations><Phase><Phenotype><Physical Function><Plasma><Plasma Serum><Plasma-Cell Myeloma><Population Heterogeneity><Public Health><Quality Control><Questionnaires><Recording of previous events><Research><Research Design><Research Personnel><Research Resources><Researchers><Resources><Reticuloendothelial System, Serum, Plasma><Saint Jude><Saint Jude Children's Cancer Center><Saint Jude Children's Research Hospital><Saliva><Sample Size><Sampling><Sampling Studies><Science><Scientist><Septicemia><Serum><Site><Skilled Nursing Facilities><Slow-Onset Diabetes Mellitus><St. Jude><St. Jude Children's Cancer Center><St. Jude Children's Research Hospital><St. Jude Children's Research Hospital Comprehensive Cancer Center><St.Jude Children's Cancer Center><St.Jude Children's Research Hospital><St.Jude Children's Research Hospital Comprehensive Cancer Center><Stable Diabetes Mellitus><Study Type><Swab><Synovia><Synovial Fluid><T2 DM><T2D><T2DM><Testing><Time><Training><Translating><Translations><Trisomy 21><Type 2 Diabetes Mellitus><Type 2 diabetes><Type II Diabetes Mellitus><Type II diabetes><Urine><Validation><Virus-HIV><Wisconsin><Work><adult onset diabetes><adulthood><aerospace travel><age associated disease><age associated disorder><age associated impairment><age dependent disease><age dependent disorder><age dependent impairment><age related human disease><age-related disease><age-related disorder><age-related impairment><aging associated mechanism><aging mechanism><aging pathway><aging process><aging related mechanism><anti aging based therapeutic><anti aging therapeutic><anti-aging property therapeutic><biobank><biological mechanism of age><biological pathways of age><biorepository><chromosome 21 trisomy syndrome><cognitive function><congenital acromicria syndrome><coronavirus disease 2019 long hauler><data management><delirious><depository><design><designing><developmental><diabetic><diet intervention><disability><diverse populations><diversity, equity, and inclusiveness><drug/agent><early-career faculty><enroll><equity, diversity, and inclusion><geroscience therapeutic><geroscientific><gerotherapeutic><glioblastoma multiforme><health-span><healthspan><healthy life span><heterogeneous population><histories><human subject><imaging><individualized approach><innovate><innovation><innovative><insulin resistant><insulin tolerance><intervention research><interventional research><interventional strategy><interventional study><interventions research><ketosis resistant diabetes><kids><life span><life style intervention><lifespan><lifestyle intervention><long hauler><malignancy><malignant breast tumor><maturity onset diabetes><measurable outcome><meeting><meetings><microbiome><minimally invasive><morbus Down><mortality><myeloma><myelomatosis><neoplasm/cancer><new approaches><novel><novel approaches><novel strategies><novel strategy><nutritious><organ allograft><organ graft><organ xenograft><outcome measurement><personalized approach><population diversity><pre-clinical><precision approach><preclinical><prevent><preventing><primary sclerosing cholangitis><pseudohypertrophic progressive muscular dystrophy><repository><response><senolytics><senomorphic><senostatic><septicaemia><septicemic><skin ulcer><space travel><spongioblastoma multiforme><study design><success><tailored approach><targeted agent><therapeutic against aging><therapeutic interventions against aging><therapeutic strategies for aging><therapeutic strategies targeting aging><therapeutic target for anti-aging><therapeutic targeting aging><therapeutic targets to reverse aging><therapeutic to prevent aging><therapeutics impacts on aging><therapeutics that slow aging><translation><translational study><trisomy 21 syndrome><type 2 DM><type II DM><type two diabetes><ulcerative wounds><vaccine response><vaccine responsiveness><vaccine-induced response><validations><youngster>