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Translational Geroscience Network

转化老年科学网络

基本信息

批准号：
10539281
负责人：
JAMES L. KIRKLAND
金额：
$ 78.43万
依托单位：
MAYO CLINIC ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-02-01 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10539281
关键词：
Acceleration Aging Alzheimer&apos s Disease Ancillary Study Animal Model Apoptosis Autophagocytosis Basic Science Biological Aging Biological Assay Biology Biology of Aging Biopsy Blood Body Fluids Cardiovascular Diseases Cell Aging Cells Chronic Chronic Disease Clinical Clinical Data Clinical Research Clinical Trials Communities Data Dementia Development Diabetes Mellitus Disease Drug Targeting Elderly Epidemiology Epigenetic Process FRAP1 gene Funding Future Gene Expression Geriatrics Geroscience Goals Grant Health Care Costs Health Policy Healthcare Systems Heart Diseases Human Immune response Inflammation Influenza vaccination Infrastructure Institution Intervention Laboratories Learning Life Longevity Malignant Neoplasms Mammals Manuals Measures Metformin Methods Mitochondria Morbidity - disease rate Multi-Institutional Clinical Trial Multicenter Trials Patients Pharmaceutical Preparations Phase Preclinical Testing Procedures Process Protocols documentation Publishing R24 Reporting Research Research Design Research Personnel Resources Risk Factors Sample Size Sampling Series Specimen Subgroup System Testing Time Translating Translations United States National Institutes of Health age related biobank cell mediated immune response clinical care clinical practice data management design disability drug repurposing early phase trial experience frailty glycation healthspan idiopathic pulmonary fibrosis innovation mortality novel novel strategies older women pre-clinical prevent proteostasis recruit repository sample collection senescence support network targeted agent therapy design working group

项目摘要

Aging is the leading risk factor for the disorders that account for the bulk of the nation's morbidity, mortality, and health costs. Recent findings suggest it is feasible to alleviate such disorders as a group by targeting fundamental aging processes. Several such interventions are near the point of entering human proof-of-concept clinical trials. Since interventions that increase lifespan and healthspan in mammals now exist, we hypothesize that clinical interventions targeting fundamental mechanisms of aging may delay, prevent, or treat age-related diseases and disabilities as a group, instead of one at a time. To accelerate testing this hypothesis, we propose a Translational Geroscience Network (TGN). Planning began 4 years ago through an NIA R24 grant involving 122 investigators in the biology of aging and clinical geriatrics. Our goal is to mature this network into a national resource starting with a subgroup of centers committed to working together using common measures and protocols allowing network-wide learning from complementary, small-scale, proof-of- concept “use case” clinical studies. Aim 1 is to establish a TGN to develop, implement, test, and harmonize methods and standard operating protocols (SOPs) for translational early phase trials of agents that target fundamental aging processes. The TGN will support development, coordination, and infrastructure around independently-funded “use case” trials (2-3 per year) using re-purposed drugs for which preclinical or clinical data already exist, such as a multicenter trial of senolytics for idiopathic pulmonary fibrosis, a trial of a different drug to reduce senescent cell burden and alleviate frailty in older women, and a trial of metformin to enhance immune responses to influenza vaccination. Based on these “use case” trials, we will streamline and harmonize approvals, recruitment, sample collection, SOPs, and analytic procedures across the TGN. Aim 2 is to select, optimize, and validate ancillary measures of fundamental aging processes to be assayed across all trials to establish reference analytical capabilities. An existing cell senescence assay facility will be expanded to analyze blood, other body fluids, cells, and biopsies from trials across and beyond the TGN to serve as a national resource. New assays will be developed and optimized. The facility will expand to include laboratories beyond the TGN and incorporate assays of key basic aging mechanisms, including mTOR activity, proteostasis, autophagy, mitochondrial function, and epigenetics. Aim 3 is to provide statistical and data management support to select efficient study designs, provide sample size estimates and support a TGN-wide data entry platform to facilitate cross-study comparisons. Aim 4 is to develop a biobanking and repository network for samples from the clinical trials to permit future analyses as new ancillary research questions are developed and assays become available. A system for disseminating samples to the basic biology of aging community, biobanking protocols, and operating manuals will be developed. Translating agents targeting basic aging processes into interventions for the major chronic diseases and age-related disabilities could be transformative.

老龄化是疾病的主要危险因素，占全国发病率，死亡率和死亡率的大部分。医疗费用。最近的研究结果表明，通过靶向治疗，基本的衰老过程有几种这样的干预措施已经接近进入人类概念验证阶段临床试验由于现在存在增加哺乳动物寿命和健康寿命的干预措施，假设针对衰老基本机制的临床干预可以延缓，预防，或将与年龄有关的疾病和残疾作为一个群体来治疗，而不是一次一个。为了加速测试假设，我们提出了一个翻译老年科学网络（TGN）。计划始于4年前， NIA R24资助涉及122名衰老生物学和临床老年病学研究人员。我们的目标是让这个从致力于共同工作的中心小组开始，共同的措施和协议，允许全网络的学习，从互补的，小规模的，概念“用例”临床研究。目标1是建立一个TGN来开发、实施、测试和协调方法和标准操作规程（SOP），用于药物的转化早期试验，针对基本的衰老过程。TGN将支持开发、协调和基础设施围绕独立资助的“用例”试验（每年2-3次），使用临床前或临床数据已经存在，例如用于特发性肺纤维化的senolytics的多中心试验，不同的药物，以减少衰老细胞的负担，减轻老年妇女的脆弱性，和二甲双胍的试验，增强对流感疫苗的免疫反应。基于这些“用例”试验，我们将简化和协调整个TGN的批准、招募、样本收集、SOP和分析程序。目标二是选择、优化和验证待分析的基本老化过程的辅助措施，所有试验都是为了建立参考分析能力。现有的细胞衰老检测设施将扩大分析血液，其他体液，细胞和活检从试验跨越和超越TGN，作为一个国家资源。将开发和优化新的检测方法。该设施将扩大到包括实验室超越TGN，并结合关键的基本衰老机制的测定，包括mTOR活性，蛋白抑制，自噬、线粒体功能和表观遗传学。目标3是提供统计和数据管理支持选择有效的研究设计，提供样本量估计并支持TGN范围内的数据输入平台，以促进跨研究比较。目标4是建立一个生物库和储存库网络，从临床试验中提取样本，以便在开发新的辅助研究问题时进行未来分析并且分析变得可用。一种用于向老龄化社区的基础生物学传播样本的系统，将制定生物库方案和操作手册。针对基础老化的翻译代理将这一进程转化为主要慢性病和与年龄有关的残疾的干预措施可能具有变革性。