RC1: Pre-Clinical Research Core

RC1：临床前研究核心

• 批准号: 10028131
• 负责人: Adam Salmon
• 金额: $ 21.32万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10028131
• 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; 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”.

已显示几种干预措施可促进啮齿动物的健康寿命。但是，类似 对健康人的预期，介入的寿命研究极为挑战。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OAIC研究人员使用常见的Marmoset（Callithrix Jacchus）作为临床前模型 用于翻译的Geroscience研究。 RC1的重点是摩尔马斯人作为临床前模型，原因有几个： a）它们是相对短暂的非人类素数； b）果果小（300-500 g），需要更少 饲养和复合管理的费用； c）可以在其通常的社会 配置； d）它们自然与年龄相关的病理的谱与人类相当； e）它们允许评估无法轻易收集在人的组织中的干预措施（例如大脑， 心脏，肾脏，肝脏）。反映了对该模型的兴趣，NIA最近发布了一个标题为“ RFA” “将摩尔马人的表征描述为衰老和与年龄有关的疾病的模型”。 RC1通过以下特定目的实现了其使命：1）欧盟调查人员访问 衰老的果果的独特殖民地； 2）提供研究衰老干预措施对影响的资源 Marmoset HealthSpan； 3）提供并维护整个年龄范围内的摩尔果的组织； 4） 提供评估Marmosets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，另外13个项目 外部项目。 RC1向另外16位科学家提供了组织。 RC1的其他主要成就包括： •执行多种摩尔果的衰老表型的初始表征，包括功能变化 随着执行功能，肾脏病理，心血管健康，免疫功能和微生物组的年龄； •进行第一个研究测试，是否通过药物延长非人类灵长类动物的寿命 干预（雷帕霉素）； •对二甲双胍，acarbose和17α-雌二醇进行早期药理学和耐受性研究 将奠定长期寿命和HealthSpan试验的基础； •协助OAIC学者和飞行员赠款收件人成功从多个外部来源获得资金 （NIA，NIDCR和AFAR）用摩尔马人扩展和扩展他们的研究；和 •增强Marmoset模型的可见性，并在全国范围内促进这种宝贵的资源。 在下一个奖励周期中，RC1将支持2名飞行员，1名学者和10个外部项目。 RC1也将支持 两个具有高度创新功能的发展项目（DPS）：DP1标题为“人类武器比较 评估MTOR在心脏衰老中的作用”和DP2的标题为“衰老的比较脂肪组学”。