RC1: Pre-Clinical Research Core

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，类比 在健康人群中进行的前瞻性、干预性寿命研究极具挑战性。临床前 SA OAIC的研究核心（RC 1）通过提供知识，技能和技术来解决这一障碍。 支持OAIC研究人员使用普通绒猴（Callithrix jacchus）作为临床前模型 用于老年科学的转化研究RC 1专注于将绒猴作为临床前模型，原因如下： a）它们是相对短寿命的非人类灵长类动物; B）绒猴很小（300-500 g），需要较少的能量。 饲养和复合管理的成本; c）绒猴可以维持在它们通常的社会环境中， d）它们的自然发生的年龄相关病理学谱与人类的谱相当; 和e）它们允许评估在人体内不能容易收集的组织（例如脑， 心脏、肾脏、肝脏）。为了反映对这种模式的兴趣，NIA最近发布了一份RFA， “作为衰老和衰老相关疾病模型的绒猴特征”。 RC 1通过以下具体目标实现其使命：1）向OAIC调查员提供访问 衰老绒猴的独特群体; 2）提供研究衰老干预措施对 绒猴健康span; 3）提供并维持来自各年龄段绒猴的组织库; 4） 提供评估绒猴分析药理学的服务;和5）支持研究培训和 OAIC的传播任务。 在最初的奖励周期，RC 1成功地协助了13个OAIC资助的项目和另外13个项目。 外部项目。RC 1为另外16名科学家提供了组织。RC 1的其他主要成就包括： ·对绒猴的几种老化表型进行初步表征，包括功能变化 随着年龄的增长，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，测试非人类灵长类动物的寿命是否可以通过药物延长 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学者和试点赠款获得者成功地从几个外部来源获得资金 (NIA，NIDCR和AFAR），以扩大和扩展他们对绒猴的研究; ·提高绒猴模型的知名度，并在全国范围内推广使用这一宝贵资源。 在下一个奖励周期，RC 1将支持2个试点项目，1个学者和10个外部项目。RC 1还将支持 两个具有高度创新特点的发展项目：发展项目1，题为“人类-绒猴比较 评估mTOR在心脏衰老中的作用”，以及题为“衰老的比较脂质组学”的DP 2。

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”.