RC1: Pre-Clinical Research Core

RC1：临床前研究核心

• 批准号: 10221556
• 负责人: Adam Salmon
• 金额: $ 23.2万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-06-15 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10221556
• 关键词: Acarbose; Address; Affect; Age; Aging; American; Award; Biology of Aging; Brain; Callithrix; Callithrix jacchus jacchus; Capsicum; Cardiac; Cardiovascular system; Clinical Research; Collagen; Country; Deposition; Development; Disease; Educational workshop; Elastin; Elderly; Estradiol; FRAP1 gene; Foundations; Funding; Geroscience; Grant; Heart; Human; Intervention; Kidney; Knowledge; Life Extension; Lipids; Liver; Longevity; Magnetic Resonance Imaging; Measurement; Metformin; Mission; Modeling; Myocardial dysfunction; National Institute of Dental and Craniofacial Research; Pathology; Pharmacologic Substance; Pharmacology; Phase; Phenotype; Plasma; Play; Pre-Clinical Model; Primates; Process; Research; Research Design; Research Personnel; Research Support; Research Training; Resources; Rodent; Role; Sampling; Scientist; Services; Shock; Signal Pathway; Sirolimus; Source; Technology; Testing; Tissue Banks; Tissue Sample; Tissues; Training; Translating; Translations; United States National Institutes of Health; age effect; age related; aged; base; cardiovascular health; comparative; cost; executive function; gut microbiome; healthspan; healthy aging; immune function; improved; innovation; interest; lipidome; lipidomics; meetings; microbiome; nonhuman primate; novel; pre-clinical; pre-clinical research; programs; prospective; research data dissemination; skills; social; success; symposium; translational model

Several interventions have been shown to promote healthy life extension in rodents. However, analogous prospective, interventional lifespan studies in healthy people are extremely challenging. The Pre-clinical Research Core (RC1) of the SA OAIC addresses this barrier by providing the knowledge, skills, and technical support to assist OAIC investigators in using the common marmoset (Callithrix jacchus) as a pre-clinical model for translational geroscience research. RC1 focuses on marmosets as a pre-clinical model for several reasons: a) They are relatively short-lived nonhuman primates; b) marmosets are small (300-500 g), requiring less costs for husbandry and compound administration; c) marmosets can be maintained in their usual social configurations; d) their spectrum of naturally-occurring age-related pathologies is comparable to that of humans; and e) they allow assessment of interventions in tissues that cannot be readily collected in people (e.g. brain, heart, kidney, liver). Reflecting the interest in this model, the NIA recently released an RFA entitled “Characterization of Marmosets as Models of Aging and Age-Related Diseases”. RC1 achieves its mission through the following Specific Aims: 1) Provide OAIC investigators access to a unique colony of aging marmosets; 2) Provide resources required for studying effects of aging interventions on marmoset healthspan; 3) Provide and maintain a bank of tissues from marmosets across the age range; 4) Provide services to assess analytical pharmacology in marmosets; and 5) Support the research training and dissemination missions of the OAIC. During the initial award cycle, RC1 successfully assisted 13 OAIC funded projects and an additional 13 external projects. RC1 provided tissues to 16 more scientists. Other key accomplishment of RC1 include: • Perform the initial characterization of several aging phenotypes of marmosets, including functional changes with age in executive function, kidney pathology, cardiovascular health, immune function, and the microbiome; • Conduct the first study testing whether nonhuman primate lifespan is extended by a pharmaceutical intervention (rapamycin); • Carry out early-phase pharmacology and tolerability studies with metformin, acarbose and 17α-estradiol that will lay the foundation for long-term lifespan and healthspan trials; • Assist OAIC Scholars and pilot grant recipients to successfully obtain funding from several external sources (NIA, NIDCR, and AFAR) to expand and extend their studies with marmosets; and • Enhance the visibility of the marmoset model and promote use of this valuable resource across the country. During the next award cycle, RC1 will support 2 pilot, 1 Scholar and 10 external projects. RC1 also will support two developmental projects (DPs) with highly innovative features: DP1 entitled “Human-marmoset comparative assessment of the role of mTOR in cardiac aging”, and DP2 entitled “Comparative lipidomics of aging”.

一些干预措施已被证明可以促进啮齿动物的健康寿命延长。然而，类似的 对健康人进行前瞻性、介入性寿命研究极具挑战性。临床前 SA OAIC 的研究核心 (RC1) 通过提供知识、技能和技术来解决这一障碍 支持协助 OAIC 研究人员使用普通狨猴 (Callithrix jacchus) 作为临床前模型 用于转化老年科学研究。 RC1 重点关注狨猴作为临床前模型，原因如下： a) 它们是寿命相对较短的非人类灵长类动物； b) 狨猴较小（300-500 克），需要较少 畜牧业和饲养场管理费用； c) 狨猴可以保持正常的社交状态 配置； d) 他们自然发生的与年龄相关的病理范围与人类相当； e) 它们允许评估对人体组织中不易收集的干预措施（例如大脑、 心、肾、肝）。 NIA 最近发布了一篇题为“RFA”的 RFA，反映了人们对这一模型的兴趣 “狨猴作为衰老和年龄相关疾病模型的特征”。 RC1 通过以下具体目标实现其使命： 1) 为 OAIC 调查人员提供访问 独特的老龄狨猴群落； 2) 提供研究老龄化干预措施对健康的影响所需的资源 狨猴的健康寿命； 3) 提供并维护一系列来自不同年龄段狨猴的组织； 4） 提供评估狨猴分析药理学的服务； 5) 支持研究培训和 OAIC 的传播任务。 在最初的奖励周期中，RC1 成功协助了 13 个 OAIC 资助的项目和另外 13 个项目 外部项目。 RC1 向另外 16 名科学家提供了组织。 RC1 的其他主要成就包括： • 对狨猴的几种衰老表型进行初步表征，包括功能变化 与年龄相关的执行功能、肾脏病理、心血管健康、免疫功能和微生物组； • 进行第一项研究，测试药物是否可以延长非人类灵长类动物的寿命 干预（雷帕霉素）； • 开展二甲双胍、阿卡波糖和 17α-雌二醇的早期药理学和耐受性研究， 将为长期寿命和健康寿命试验奠定基础； • 协助 OAIC 学者和试点资助获得者成功从多个外部来源获得资金 （NIA、NIDCR 和 AFAR）扩大和延伸他们对狨猴的研究；和 • 提高狨猴模型的知名度并促进在全国范围内利用这一宝贵资源。 在下一个奖励周期中，RC1 将支持 2 个试点项目、1 个学者项目和 10 个外部项目。 RC1也将支持 两个具有高度创新特征的发展项目（DP）：DP1，题为“人类与狨猴的比较” mTOR 在心脏衰老中的作用评估”，DP2 题为“衰老的比较脂质组学”。