Translational Geroscience Network

老龄化是疾病的主要风险因素，这些疾病占国家发病率、死亡率和 医疗费用。最近的发现表明，作为一个群体，通过靶向治疗来缓解此类疾病是可行的 基本的老化过程。几个这样的干预接近进入人类概念验证的点 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群体来对待，而不是一次一个。要加速测试，请执行以下操作 假设，我们提出了一个翻译老年科学网络(TGN)。规划始于4年前，通过 NIA R24赠款涉及122名衰老生物学和临床老年病学的研究人员。我们的目标是使之成熟 从致力于合作的中心的子组开始，将网络转化为国家资源 通用措施和协议，允许在整个网络范围内从互补性、小规模、经验证的 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 用于以下药物的翻译早期试验的方法和标准操作规程(SOP) 针对基本老化过程。TGN将支持发展、协调和基础设施 围绕独立资助的使用案例试验(每年2-3个)，使用临床前或临床前或 临床数据已经存在，例如一项针对特发性肺纤维化的敏感剂多中心试验，一项关于 不同药物减轻老年妇女衰老细胞负担和缓解虚弱，以及二甲双胍治疗老年妇女的试验 加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、标准操作规程和分析程序。目标2是 选择、优化和验证要进行分析的基本老化过程的辅助措施 所有试验以建立参考分析能力。将扩大现有的细胞衰老检测设备 分析血液、其他体液、细胞和来自TGN内外试验的活组织检查，作为 国家资源。将开发和优化新的分析方法。该设施将扩大到包括实验室 除TGN外，还包括关键基本衰老机制的分析，包括mTOR活性、蛋白稳定、 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范围的数据输入 促进交叉研究比较的平台。目标4是开发一个生物库和存储库网络，用于 来自临床试验的样本，以允许在开发新的辅助研究问题时进行未来分析 化验方法也变得可用。一种将样本传播到老龄化社区的基础生物学的系统， 将制定生物库协议和操作手册。以基本衰老为目标的翻译代理 重大慢性病和与年龄相关的残疾的干预进程可能具有变革性。

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.