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，这些因素可能加速或延迟衰老，降低或增加疾病风险和/或促进寿命延长。因此，评估遗传变异在衰老中的作用需要一种实验策略，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，JAX国家安全委员会寻求支持，以进一步开发和传播下一代遗传、统计和信息资源，这些资源是实现全系统方法来理解健康老龄化所必需的。JAX NSC改变了JAX的老龄化研究，为我们的研究人员提供了中心资源，在上一个资助期内，我们已经发表了38篇同行评审的出版物和几项积极的资助。该中心已经开发了用于衰老研究的新兴区域和国家资源，包括遗传图谱，新颖的统计方法和衰老小鼠资源和组织，这些资源和组织支持我们众多的合作和外部研究人员。所有JAX NSC数据都在小鼠表型数据库和JAX NSC网站上公开发布，从而确保通过该中心生成的资源和获得的专业知识随时可供老龄化研究界使用。在这次更新中，我们将向我们的目标迈进，为老龄研究人员提供下一代资源和支持，同时利用JAX在小鼠复杂多基因性状的大规模鉴定和功能验证方面无与伦比的专业知识。我们的具体目标是：1)增加可用于衰老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-饮食相互作用；2)加强老龄社区可用的统计工具和支持；3)扩大遗传方法在衰老转化研究中的应用，即通过对候选人类衰老基因的强大筛选管道；4)通过强大的研究开发核心，扩大JAX对老龄化、健康和年龄相关疾病的研究重点；5)提供有效的中心管理，提高JAX NSC资源在整个老龄化社区的利用率。该中心将由经验丰富的首席研究员和核心领导团队领导，他们将与JAX国家安全委员会成员一起，并在外部咨询委员会的监督下，提供有效的管理，以促进中心的目标和目标。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，并利用其为老龄化研究界产生的资源。

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.