RC1: Pre-Clinical Research Core

RC1：临床前研究核心

• 批准号: 10455767
• 负责人: Adam Salmon
• 金额: $ 21.26万
• 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/10455767
• 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; Persons; 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”.

已证明有几种干预措施可以促进啮齿动物的健康寿命延长。然而，类比 健康人群的前瞻性、干预性寿命研究极具挑战性。临床前 SA OAIC的研究核心(RC1)通过提供知识、技能和技术 支持OAIC研究人员使用常见的绒猴(Callithrix Jacchus)作为临床前模型 用于翻译老年学研究。Rc1专注于将绒猴作为临床前模型，原因如下： A)它们是寿命相对较短的非人类灵长类动物；b)绒猴体型较小(300-500克)，需要较少的 饲养和复合管理的费用；c)绒猴可以维持它们通常的社会生活 它们的自然发生的与年龄相关的病理谱与人类的谱相似； 以及e)它们允许评估在人体内不容易收集的组织中的干预(例如，大脑， 心脏、肾脏、肝脏)。反映了人们对这种模式的兴趣，NIA最近发布了一份名为 “将绒猴定性为衰老和与年龄有关的疾病的模型”。 Rc1通过以下具体目标实现其使命：1)向审查处调查人员提供 独特的老化绒猴群体；2)提供所需资源，用于研究老龄化干预对 绒猴健康跨度；3)提供和维护不同年龄段的绒猴组织库；4) 提供服务以评估绒猴的分析药理学；以及5)支持研究、培训和 伊斯兰会议组织的传播任务。 在最初的颁奖周期中，RC1成功地援助了13个由伊斯兰会议组织资助的项目和另外13个项目 外部项目。Rc1为另外16名科学家提供了组织。RC1的其他主要成就包括： ·对几种老化的绒猴表型进行初步鉴定，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，测试一种药物是否延长了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-雌二醇的早期药理和耐受性研究 将为长期寿命和健康跨度试验奠定基础； ·协助海湾合作组织奖学金获得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)扩大和扩大他们对绒猴的研究；以及 ·提高绒猴模式的知名度，并在全国推广利用这一宝贵资源。 在下一个获奖周期内，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 具有高度创新性的两个发展项目(DP)：DP1题为“人与绒猴的比较” 评估mTOR在心脏老化中的作用“，以及DP2，题为”衰老的比较脂质组学“。