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.

衰老是解释该国大部分发病率，死亡率和健康成本。最近的发现表明，通过靶向来减轻此类疾病是可行的基本的老化过程。几种这样的干预措施接近进入人类概念证明临床试验。由于现在存在增加哺乳动物寿命和健康状态的干预措施，我们假设针对衰老基本机制的临床干预措施可能会延迟，预防，或将与年龄有关的疾病和疾病视为一个组，而不是一次。加速测试假设，我们提出了一个翻译的Geroscience网络（TGN）。计划从4年前开始 NIA R24赠款涉及122名衰老和临床老年医学生物学的研究者。我们的目标是成熟网络进入国家资源，从一群致力于共同努力合作的中心开始常见的测量和协议，允许从完成，小规模，证明概念“用例”临床研究。 AIM 1是建立一个TGN来开发，实施，测试和协调方法和标准操作方案（SOP），用于翻译代理的早期试验目标基本衰老过程。 TGN将支持开发，协调和基础设施使用重新组合的药物或临床前的药物，围绕独立资助的“用例”试验临床数据已经存在，例如针对特发性肺纤维化的鼻溶剂的多中心试验，这是一项试验不同的药物以减少感官细胞伯嫩并减轻老年妇女的脆弱性，以及对二甲双胍的试验增强对影响力疫苗接种的免疫反应。基于这些“用例”试验，我们将简化和整个TGN的批准，招聘，样本收集，SOP和分析程序。 AIM 2是选择，优化和验证要分配的基本老化过程的辅助度量所有试验以建立参考分析能力。现有的细胞感应测定设施将扩大分析来自TGN和以外试验的血液，其他体液，细胞和活检国家资源。新测定将开发和优化。该设施将扩展到包括实验室除了TGN并结合了关键基本衰老机制的测定，包括MTOR活性，蛋白质，自噬，线粒体功能和表观遗传学。 AIM 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范围内的数据输入促进跨研究比较的平台。 AIM 4是开发一个生物库和存储库网络随着新的辅助研究问题的开发，临床试验的样本允许将来进行分析和测定可用。将样品传播到衰老社区的基本生物学的系统，将制定生物库协议和操作手册。翻译针对基本衰老的代理对主要慢性疾病和与年龄相关的疾病进行干预的过程可能是有害的。