Shock Center for Aging Research at The Jackson Laboratory

描述（由申请人提供）：人类遗传变异在调节寿命差异以及整体健康和疾病易感性随年龄变化方面发挥着重要作用。了解遗传变异和衰老生物学之间的联系有望最终确定延长人类健康寿命的方法。然而，健康寿命是一个复杂的性状，并确定相互作用的多态性等位基因和环境因素的影响是困难的。应对这一挑战将需要一种系统的方法来应对衰老，利用一种模拟人类遗传和生物复杂性的实验生物体。 杰克逊休克中心（JSC）建议利用其在小鼠模型和复杂性状方面的专业知识，在前一个资助期取得成功的基础上，开发必要的独特资源，使老龄化社区能够阐明健康寿命的遗传基础。具体而言，JSC将提供： 1)通过大型杂交和参考种群的核心，包括协作杂交系，提供前所未有的遗传变异，衰老小鼠和组织; 2）小鼠种群基因分型和全面表征与衰老和健康寿命相关的生理和行为特征; 3）开发新的统计方法，使研究人员能够识别相关性，窄QTL，以及理解衰老相关性状的因果关系与反应关系;以及4）整合小鼠和人类衰老数据，组装成小鼠和人类衰老基因座的注释遗传图谱，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，并建议翻译干预措施以延长健康寿命。所有JSC资源，方法，表型和遗传数据以及地图将通过小鼠表型数据库（MPD），JSC网站和拟议的门户网站提供，该门户网站将整合内森休克中心（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，以支持29名教师和20多个独立的，赠款资助的研究项目，旨在解开人类衰老的遗传控制在杰克逊实验室（JAX）。这些资源将被广泛传播，以支持20多个现有的合作以及众多的外部老龄化调查人员，大大扩大了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衰老上，从而为研究界提供更多的资源，并更好地了解寿命和健康的分子机制。 公共卫生相关性：人类衰老受遗传因素影响。寿命的差异以及健康和疾病风险随时间的变化与个人遗传密码的变化有关。杰克逊休克中心将开发资源，以确定遗传差异，并探讨他们在控制健康老龄化的作用。资源将包括：老年小鼠模型，反映人类遗传变异;与年龄相关的特征的生理和行为数据;以及揭示与人类衰老相关的遗传因素的方法。科学界将获得资源，加速研究，以了解并最终延长健康的人类衰老。

DESCRIPTION (provided by applicant): 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: 1) 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 for the research community and a better understanding of the molecular mechanisms of lifespan and healthspan. PUBLIC HEALTH RELEVANCE: Human aging is influenced by genetic factors. Differences in longevity as well as changes in health and disease-risk with time are linked with variation in individuals' genetic codes. The Jackson Shock Center will develop resources to identify genetic differences and probe their role in controlling healthy aging. Resources will include: aged mouse models, mirroring human genetic variation; physiological and behavioral data for age-related traits; and methods to reveal genetic factors tied to human aging. Resources will be available to the scientific community, accelerating research to understand and ultimately prolong healthy human aging.