Translational Geroscience Network

转化老年科学网络

• 批准号: 10339417
• 负责人: JAMES L. KIRKLAND
• 金额: $ 77.68万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-01 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10339417
• 关键词: Aging; Alzheimer' 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; Monoclonal Antibody R24; Morbidity - disease rate; Multi-Institutional Clinical Trial; Multicenter Trials; Patients; Pharmaceutical Preparations; Phase; Preclinical Testing; Procedures; Process; Protocols documentation; 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; base; biobank; cell mediated immune response; clinical care; clinical practice; data management; design; disability; 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

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.

老龄化是导致该国大部分发病率、死亡率和死亡率的疾病的主要危险因素。 健康成本。最近的研究结果表明，通过针对群体来缓解此类疾病是可行的 基本的衰老过程。一些此类干预措施即将进入人类概念验证阶段 临床试验。由于现在存在延长哺乳动物寿命和健康寿命的干预措施，我们 假设针对衰老基本机制的临床干预可能会延迟、预防、 或者将与年龄相关的疾病和残疾作为一个整体来治疗，而不是一次治疗一个。为了加速测试这个 假设，我们提出了一个转化老年科学网络（TGN）。规划始于 4 年前 NIA R24 拨款涉及衰老生物学和临床老年病学领域的 122 名研究人员。我们的目标是使这个成熟 网络成为国家资源，从致力于共同使用的中心小组开始 通用措施和协议允许网络范围内的学习，从互补的、小规模的、证明的 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 用于药物转化早期试验的方法和标准操作方案（SOP） 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），使用重新调整用途的药物，其中临床前或 临床数据已经存在，例如 senolytics 治疗特发性肺纤维化的多中心试验、 减少衰老细胞负担并减轻老年女性虚弱的不同药物，以及二甲双胍的试验 增强对流感疫苗接种的免疫反应。基于这些“用例”试验，我们将简化和 协调整个 TGN 的审批、招聘、样本收集、SOP 和分析程序。目标 2 是 选择、优化和验证要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。将扩建现有的细胞衰老检测设施 分析来自 TGN 内外试验的血液、其他体液、细胞和活组织检查，作为 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 并结合关键基本衰老机制的检测，包括 mTOR 活性、蛋白质稳态、 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 方便交叉研究比较的平台。目标 4 是开发生物样本库和储存库网络 临床试验中的样本，以便在新的辅助研究问题出现时进行未来的分析 并且可以进行分析。用于将样本传播到老龄化社区基础生物学的系统， 将制定生物样本库方案和操作手册。针对基本老龄化的翻译代理 对主要慢性疾病和与年龄相关的残疾进行干预的过程可能具有变革性。