Research Deveopment Core

人类基因变异在调节寿命差异和总体变化方面发挥着重要作用 健康和疾病的易感性随年龄增长。了解基因变异和基因突变之间的联系 衰老生物学有望最终找到延长人类健康寿命的方法。然而， 健康寿命是一个复杂的特征，它决定了相互作用的多态等位基因和环境因素 这对它的影响是困难的。应对这一挑战将需要一种应对老龄化的系统方法，利用 模拟人类种群遗传和生物复杂性的实验有机体。 杰克逊休克中心(JSC)建议利用其在老鼠模型和复杂特征方面的专业知识来建立 关于上一个供资期间取得的成功，并开发必要的独特资源，使 老龄化社区，以阐明健康寿命的遗传基础。具体地说，JSC将提供： ^)通过大杂交和参考种群的中心核心使小鼠和组织老化，包括 协作性交叉系，提供前所未有的遗传变异；2)小鼠群体进行基因分型和 全面描述与衰老和健康有关的生理和行为特征； 3)开发了新的统计方法，使研究人员能够识别相关性，缩小QTL，并 了解衰老相关特征的因果关系和反应关系；以及4)整合老鼠和人 将老化数据合并到带注释的老鼠和人类衰老基因图谱中，以使研究人员能够 快速识别和验证与人类衰老有关的基因，并提出翻译干预建议 延长健康寿命。所有JSC资源、方法、表型和遗传数据以及图谱都将公开 可通过鼠标表现组数据库(MPD)、JSC网站和拟议的网络门户网站获得，该门户网站 将整合内森冲击中心(NSC)的资源和信息。 JSC将提供前所未有的、协调的老龄化资源和充满活力的智力环境 支持29名教员和20多个独立的、由补助金资助的研究项目，旨在解开 杰克逊实验室(JAX)对人类衰老的基因控制。这些资源将广泛地 传播以支持20多个现有协作以及众多外部老化 研究人员，极大地扩大了JSC作为国家老龄化研究中心的作用。从长远来看，JSC将 继续将JAX在基因组学和生物学方面的专业知识集中在老龄问题上，从而使资源得到增强 研究社区和更好地理解寿命和健康的分子机制。

Human genetic variation plays a significant role in regulating differences in longevity and changes in overall health and disease susceptibility with age. Understanding the links between genetic variation and the biology of aging promises to ultimately identify approaches to extend the human healthspan. However, healthspan is a complex trait, and determining the interacting polymorphic alleles and environmental factors that affect it is difficult. Meeting this challenge will require a systems approach to aging, utilizing an experimental organism that models the genetic and biological complexity of the human population. The Jackson Shock Center (JSC) proposes to use its expertise in mouse models and complex traits to build on successes of the previous funding period and to develop the unique resources necessary to enable the aging community to elucidate the genetic underpinnings of healthspan. Specifically, JSC will provide: ^) Aging Mice & Tissues through a central core of large crosses and reference populations, including the Collaborative Cross lines, which offer unprecedented genetic variation; 2) Mouse populations genotyped and comprehensively characterized for physiological and behavioral traits relevant to aging and healthspan; 3) Novel Statistical Methods developed to enable researchers to identify correlations, narrow QTL, and to understand causal versus reactive relationships of aging related traits; and 4) Integrated Mouse and Human Aging Data assembled into an annotated genetic map of mouse and human aging loci to enable researchers to rapidly identify and validate genes implicated in human aging and to suggest translational interventions to extend healthspan. All JSC resources, methods, phenotypic and genetic data, and maps will be publically available through the Mouse Phenome Database (MPD), the JSC website, and a proposed web portal, which will integrate the resources and information of the Nathan Shock Centers (NSC). JSC will provide unprecedented, coordinated aging resources and a vibrant intellectual environment to support 29 faculty and more than 20 independent, grant-funded research projects aimed at unraveling genetic control of human aging at The Jackson Laboratory (JAX). These resources will be broadly disseminated to support more than 20 existing collaborations as well as numerous external aging investigators, greatly expanding JSC's role as a center for national aging research. In the long term, JSC will continue to focus JAX expertise in genomics and biology on aging, leading to enhanced resources forth research community and a better understanding of the molecular mechanisms of lifespan and healthspan.