Nathan Shock Center for Excellence in Basic Biology of Aging

项目概要 健康寿命是一个复杂的性状，受许多相互作用的多态等位基因和环境因素的影响， 可以加速或延缓衰老，降低或增加疾病风险，和/或促进延长寿命。因此，在本发明中， 评估遗传变异在衰老中的作用需要一种能够模拟遗传变异的实验策略。 和生物复杂性，同时允许有效识别和验证 候选基因通过这项建议，JAX NSC寻求支持，以进一步制定和传播下一个 产生必要的遗传、表型和信息资源，以实现全系统的方法， 了解健康老龄化。在过去的15年里，JAX NSC改变了衰老研究， JAX和整个老年科学界，提供中央资源，以支持调查人员， 在上一个供资期内，出版了26份经同行审查的出版物。该中心已开发出新兴的区域性 和国家资源老化研究，包括老化的老鼠资源和组织，支持我们的研究。 许多合作和外部研究人员。所有JAX NSC数据和工具都在 小鼠表型组数据库和JAX NSC网站，从而确保所产生的资源和专门知识 通过该中心获得的信息随时可供老龄化研究界使用。在这次更新中，我们将推进 通过为老年科学研究人员提供独特的资源，工具和支持，同时利用 JAX在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 对小鼠我们将通过提供有效的中心管理和增强JAX NSC的实用性来实现这一点 整个老龄化社区的资源（目标1）;扩大对老龄化，健康跨度和 通过一个强大的研发核心（目标2）， 可用于衰老研究的资源，包括一项新的研究，首次调查遗传因素对衰老的影响。 细胞衰老的变化和衰老药物的治疗（目标3）;加强数据和 为老龄化社区提供计算和支持（目标4）;扩大机器学习的使用 解释衰老病理学的技术（目标5）。该中心将由一个经验丰富的团队领导 在外部咨询委员会的监督下， 有效的管理，以促进中心的目标和宗旨。该中心将利用无与伦比的 杰克逊实验室是一家全球知名的研究机构， 小鼠遗传学研究，以提高其目标和它为衰老研究产生的资源的效用 社区

OVERALL—PROJECT SUMMARY Healthspan 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, phenotyping, and information resources necessary to enable a systems-wide approach to understanding healthy aging. Over the past 15 years, The JAX NSC has transformed aging research both at JAX and across the geroscience community, providing central resources to support investigators that have resulted in 26 peer-reviewed publications in the last funding period. The Center has developed nascent regional and national resources for aging research, including aging mouse resources and tissues that support our numerous collaborations and external researchers. All JAX NSC data and tools 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 is readily available to the aging research community. In this renewal, we will advance towards our goal by providing unique resources, tools, and support to geroscience investigators while leveraging JAX's unparalleled expertise in the large-scale identification and functional validation of complex polygenic traits in mice. We will do this by providing effective Center administration and enhancing the utility of JAX NSC resources throughout the aging community (Aim 1); expanding the research focus on aging, healthspan and age-related diseases through a robust Research Development Core (Aim 2); increasing the diversity of mouse resources available for aging research, including a new study to, for the first time, investigate the effect of genetic variation on cellular senescence and treatment with senolytic drugs (Aim 3); strengthening the data and computational and support available to the aging community (Aim 4); expanding the use of machine learning technologies in interpretation of aging pathologies (Aim 5). The Center will be led by a highly experienced team of Principal Investigators and Core Leaders who, with oversight from an External Advisory Board, will provide effective management to facilitate the goals and objectives of the Center. The Center will leverage 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.