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

作为对RFA-AG-20-007的回应，我们通过利用圣安东尼奥绒猴衰老计划（SA MAP）的专业知识和资源，解决FOA“促进绒猴作为衰老和年龄相关疾病研究实验室动物的表征”。在过去的十年中，SA MAP为我们理解衰老绒猴中发生的生理和功能变化做出了重大贡献，包括生理（代谢，身体组成等），功能（认知、心血管等），病理学和分子学。此外，SA MAP处于使用绒猴进行老年科学研究的最前沿，并指导研究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，采取跨学科的方法来解决存在于绒猴随年龄变化中的基本问题，并满足我们的总体目标，即表征并提供绒猴资源用于老年科学研究。衰老科学的绒猴特征，特别是在老化的标志方面，将提供一个有价值的临床前模型，用于翻译，明确定义老化如何影响可识别的生理，病理和细胞/分子结果。此外，绒猴将是一个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，其对年龄相关健康的影响，甚至在人类翻译之前对绒猴寿命的影响。这项工作的基本原理是，利用功能测定将确定生物标志物，可以链接到衰老的表型综合征。基于我们的优势，我们还将测试抗衰老干预措施对这些功能测定结果的影响程度，以确定它们是否可以用作绒猴衰老的指标。也许最重要的是，能够致力于这项研究的SA MAP资源是其他地方无法比拟的; SA MAP维持了约100只老年和老年（5-18岁）绒猴以及组织库（例如，肾、肝、脑）。我们的第一个目标是阐明和建立绒猴的年龄影响衰老的程度。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，以加强绒猴在老年科学中的基础。我们的第三个目标是扩大协同跨学科研究团队，以进一步发展尖端研究。通过建立协同研究关系，预计该提案的资助将阐明老年科学中有关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.