Translational Geroscience Network

转化老年科学网络

基本信息

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
项目类别：
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&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 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

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。最近的研究结果表明，通过针对群体来减轻此类疾病是可行的。一些这样的干预措施即将进入人类概念验证阶段。由于现在存在延长哺乳动物寿命和健康的干预措施，我们针对衰老基本机制的临床干预措施可能会延缓、预防、或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。假设，我们提出了一个转化老年科学网络（TGN），该网络于 4 年前通过一项计划开始。 NIA R24 资助项目涉及衰老生物学和临床老年病学领域的 122 名研究人员，我们的目标是使这一研究更加成熟。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） TGN 将支持发展、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、不同的药物可以减少衰老细胞负担并减轻老年妇女的虚弱，并进行了二甲双胍试验增强对流感疫苗的免疫反应根据这些“用例”试验，我们将简化和改进。目标 2 是协调整个 TGN 的批准、招募、样本收集、SOP 和分析程序。选择、优化和验证要分析的基本老化过程的辅助措施所有旨在建立参考分析能力的试验都将得到扩展。分析来自 TGN 内外试验的血液、其他体液、细胞和活组织检查，作为国家资源将被开发和优化，该设施将包括实验室。除了 TGN 之外，检测还结合了关键的基本衰老机制，包括 mTOR 活性、蛋白质稳态、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 范围内的数据输入目标 4 是开发生物样本库和存储库网络。临床试验中的样本可以在新的辅助研究问题出现时进行未来的分析一种用于将样本传播到老龄化社区基础生物学的系统，将开发针对基本老龄化的生物样本库协议和操作手册。对主要慢性疾病和与年龄相关的残疾进行干预的进程可能具有变革性。