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

圣安东尼奥 MAP 将狨猴描述为老年科学模型

• 批准号: 10260420
• 负责人: Corinna Nicole Ross
• 金额: $ 45.83万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-15 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10260420
• 关键词: Acarbose; Address; Affect; Aftercare; Age; Aging; Animal Experimentation; Animal Model; Animals; Area; Basic Science; Biological; Biological Assay; Biological Markers; Biology; Body Composition; Brain; Callithrix; Cardiovascular system; Cell Aging; Cell physiology; Chronology; Cognition; Cognitive; Disease; Education; Educational workshop; Effectiveness; Elderly; Environment; Etiology; Foundations; Funding; Gene Expression; Geroscience; Goals; Health; Human; Individual; Inflammation; Institution; Interdisciplinary Study; Intervention; Intervention Studies; Kidney; Laboratory Animals; Leadership; Link; Liver; Longevity; Metabolic; Metabolism; Metformin; Methods; Mitochondria; Modeling; Molecular; Outcome; Pathologic; Pharmacologic Substance; Pharmacology; Phenotype; Physiological; Population; Pre-Clinical Model; Preclinical Testing; Primates; Research; Research Personnel; Resources; Rodent; Sampling; Sirolimus; Syndrome; Testing; Time; Tissue Banks; Translations; Work; age effect; age related; aged; anti aging; clinical application; experience; functional decline; functional outcomes; high risk; interdisciplinary approach; interest; model development; next generation; nonhuman primate; pre-clinical; programs; resilience; response; tool; translation to humans

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.

作为对RFA-AG-20-007的回应，我们要求FOA利用圣安东尼奥绒猴衰老计划（SA MAP）的专业知识和资源，“促进绒猴作为衰老和与年龄相关疾病研究的实验动物的特征”。在过去的十年中，SA MAP为我们理解老化狨猴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）、病理和分子。此外，SA MAP在将狨猴用于老年科学方面处于领先地位，并指导研究解决衰老干预对狨猴寿命的影响。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，采用跨学科的方法来解决狨猴随年龄变化而存在的基本问题，并实现我们的总体目标，即表征狨猴并为老年科学研究提供狨猴资源。在老年科学中，狨猴的特征，特别是在衰老的特征方面，将为翻译提供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，狨猴将是一个有价值的临床前工具，用于在药理学方面测试潜在的干预策略，它们对年龄相关健康的影响，甚至在人类翻译之前对狨猴的寿命的影响。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志物。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分析结果的影响程度，以确定它们是否可以用作狨猴衰老的指标。也许最重要的是，能够用于这项研究的SA MAP资源是其他地方无法比拟的；SA MAP保存了约100只老龄和老年（5-18岁）狨猴，以及从各个年龄段的动物身上收集的组织库（如肾、肝、脑）。我们的第一个目标是阐明和确定绒猴年龄对衰老特征的影响程度。我们的第二个目标是确定短期抗衰老干预在多大程度上改变了绒猴衰老和功能表型的特征，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的跨学科研究团队，进一步发展前沿研究。通过建立协同研究关系，预计该提案的资助将阐明关于猴猴模型在老年科学中的研究成果，并开发下一代使用这种动物的前沿研究。