Characterization of Marmosets as a Geroscience Model by the San Antonio MAP

为响应RFA-AG-20-007，我们致力于通过利用圣安东尼奥Marmoset老龄计划(SA MAP)的专业知识和资源，促进将绒猴描述为研究衰老和与年龄相关疾病的实验动物。在过去的十年里，SA图谱为我们理解绒猴衰老过程中发生的生理和功能变化做出了重要贡献，这些变化包括生理(代谢、身体成分等)、功能(认知、心血管等)、病理和分子。此外，SA MAP在利用绒猴进行老年科学研究方面走在了前列，并指导了研究，以解决衰老干预对绒猴寿命的影响。SA MAP建立了一个由来自不同背景的研究人员组成的互动小组，以采取跨学科的方法来解决在绒猴随年龄发生变化中存在的基本问题，并满足我们的总体目标，即表征并为老年科学研究提供绒猴资源。对绒猴进行老年学表征，特别是就衰老的特征而言，将为翻译提供一个有价值的临床前模型，明确定义衰老如何影响可识别的生理、病理和细胞/分子结果。此外，在人类翻译之前，绒猴将是一种有价值的临床前工具，用于测试潜在的干预策略，包括药理学、它们对年龄相关健康的影响，甚至它们对绒猴寿命的影响。这项工作的基本原理是，利用功能分析将识别与衰老表型综合征相关的生物标记物。在我们优势的基础上，我们还将测试抗衰老干预措施对这些功能分析结果的影响程度，以确定它们是否可以用作绒猴衰老的衡量标准。也许最重要的是，能够用于这项研究的SA图谱资源在其他地方是无与伦比的；SA图谱保存了大约100只老年和老年(5-18岁)的绒猴以及从不同年龄范围的动物那里收集的组织库(例如，肾脏、肝脏、大脑)。我们的第一个目标是阐明和确定恒河猴的年龄在多大程度上影响衰老的特征。我们的第二个目标是确定短期抗衰老干预措施在多大程度上改变了绒猴的衰老特征和功能表型，以加强绒猴在老年学上的基础。我们的第三个目标是扩大协同跨学科研究团队，进一步发展前沿研究。通过建立协同研究关系，预计这项提案的资金将阐明关于老年科学中的绒猴模型的研究结果，并利用这种动物开发下一代尖端研究。

In response to RFA-AG-20-007, we address the FOA to “facilitate the characterization of the marmoset as a laboratory animal for research on aging and age-related diseases” by leveraging the expertise and resources of the San Antonio Marmoset Aging Program (SA MAP). Over the last decade, the SA MAP has made major contributions to our understanding of the physiological and functional changes that occur in aging marmosets including physiological (metabolism, body composition, etc.), functional (cognitive, cardiovascular, etc.), pathological and molecular. Moreover, the SA MAP is at the forefront of using the marmoset for geroscience and has directed studies to address the effect of aging interventions on marmoset lifespan. The SA MAP has built an interactive group of researchers from different backgrounds to take interdisciplinary approaches to address fundamental questions that exist in the changes that occur with age in the marmoset and to meet our overarching goal to characterize and provide a marmoset resource for geroscience research. Characterization of the marmoset for geroscience, particularly in terms of the hallmarks of aging will provide a valuable preclinical model for translation with explicit definitions on how aging affects identifiable physiological, pathological and cellular/molecular outcomes. Moreover, the marmoset will be a valuable preclinical tool for testing potential intervention strategies in terms of pharmacology, their effects of age-related health and even their effects on longevity in the marmoset prior to human translation. The rationale for this work is that utilization of functional assays will identify biomarkers that can be linked to phenotypic syndromes of aging. Building on our strengths, we will also test the extent to which anti-aging interventions affect outcomes of these functional assays to identify whether they can be utilized as metrics of aging in marmosets. Perhaps most importantly, the SA MAP resources able to be devoted to this study are unmatched elsewhere; the SA MAP maintains ~100 aged and geriatric (from 5-18 yr) marmosets as well as banks of tissue (e.g., kidney, liver, brain) collected from animals across the age range. Our first aim is to elucidate and establish the extent to which chronological marmoset age affects the hallmarks of aging. Our second aim is to determine the extent to which short-term anti-aging interventions alter hallmarks of aging and functional phenotypes in the marmoset to strengthen the foundation for marmosets in geroscience. Our third aim is to expand the synergistic interdisciplinary research team to further develop cutting-edge research. By building synergistic research relationships, it is anticipated that funding of this proposal will both elucidate research findings regarding the marmoset model in geroscience as well as develop the next generation of cutting-edge research using this animal.