The Jackson Laboratory Nathan Shock Center of Excellence in the Basic Biology of Aging

描述(由申请人提供)：寿命是一个复杂的特征，受许多相互作用的多态等位基因和环境因素的影响，这些因素可能会加速或延缓衰老，降低或增加疾病风险和/或延长寿命。因此，评估遗传变异在衰老中的作用需要一种实验策略，该策略能够模拟人类群体的遗传和生物复杂性，同时允许有效地识别和验证候选基因。通过这项建议，日本宇宙航空研究开发机构NSC寻求支持，以进一步开发和传播下一代必要的遗传、统计和信息资源，以实现全系统范围内了解健康老龄化的方法。JAX NSC已经改变了JAX的老龄化研究，为我们的调查人员提供了支持的中央资源，在上一个资助期产生了38篇同行评审的出版物和几笔积极的赠款。该中心为衰老研究开发了新的区域和国家资源，包括遗传图谱、新的统计方法和衰老小鼠资源和组织，支持我们的众多合作和外部研究人员。所有JAX NSC数据都在老鼠表现组数据库和JAX NSC网站上公开传播，从而确保通过该中心产生的资源和获得的专业知识随时可供老龄研究社区使用。在这次更新中，我们将向我们的目标前进，为老龄化的研究人员提供下一代资源和支持，同时利用JAX在复杂多基因特征i小鼠的大规模识别和功能验证方面的无与伦比的专业知识。我们的具体目标是：1)增加可用于老龄研究的小鼠资源的多样性，包括一项新的大规模干预研究，以调查遗传多样性小鼠种群中基因与饮食的相互作用；2)加强老龄社区可用的统计工具和支持；3)扩大遗传方法在老龄领域翻译研究的使用，即通过强大的人类衰老候选基因筛选管道；4)通过强大的研究开发核心，扩大JAX对衰老、健康寿命和老年相关疾病的研究重点；以及5)提供有效的中心管理，并增强JAX NSC资源在整个老龄社区的效用。该中心将由一支经验丰富的首席调查员和核心领导团队领导，他们与日本宇宙航空研究开发机构NSC成员一起，在外部咨询委员会的监督下，将提供有效的管理，以促进中心的目标和目的。该中心还将利用杰克逊实验室无与伦比的机构资源、设施和专业知识，该实验室是全球知名的小鼠遗传学研究机构，以提高其目标和为老龄化研究社区产生的资源的效用。

DESCRIPTION (provided by applicant): Lifespan is a complex trait, influenced by many interacting polymorphic alleles and environmental factors that may accelerate or delay aging, reduce or increase disease risk and/or promote extended lifespan. Thus, assessing the role of genetic variation in aging requires an experimental strategy capable of modeling the genetic and biological complexity of human populations while allowing for efficient identification and validation of candidate genes. With this proposal, the JAX NSC seeks support to further develop and disseminate the next generation of genetic, statistical and information resources necessary to enable a systems-wide approach to understanding healthy aging. The JAX NSC has transformed aging research at JAX, providing central resources to support our investigators that have resulted in 38 peer-reviewed publications and several active grants in the last funding period. The Center has developed nascent regional and national resources for aging research, including genetic maps, novel statistical methods and aging mouse resources and tissues that support our numerous collaborations and external researchers. All JAX NSC data are publicly disseminated on the Mouse Phenome Database and the JAX NSC website, thus ensuring that the resources generated and expertise acquired through the Center are readily available to the aging research community. In this renewal, we will advance toward our goal by providing next-generation resources and support to aging investigators while leveraging JAX's unparalleled expertise in the large-scale identification and functional validation of complex polygenic traits i mice. Our Specific Aims are to: 1) Increase the diversity of mouse resources available for aging research, including a new large-scale intervention study to investigate gene-diet interactions in genetically diverse mouse populations; 2) Strengthen statistical tools and support available to the aging community; 3) Expand the use of genetic approaches to translational research in aging, namely through a robust screening pipeline for candidate human aging genes; 4) Expand the research focus on aging, healthspan and age-related diseases at JAX through a robust Research Development Core; and 5) Provide effective Center administration and enhance the utility of JAX NSC resources throughout the aging community. The Center will be led by a highly experienced team of Principal Investigators and Core Leaders who, together with JAX NSC members and with oversight from an External Advisory Board, will provide effective management to facilitate the goals and objectives of the Center. The Center will also leverage the unparalleled institutional resources, facilities and expertise of The Jackson Laboratory, a globally renowned institution for mouse genetics research, to enhance its goals and the utility of the resources it generates for the aging research community.