Project 1: Frailty And Comorbidity As Cause And Consequence Of Aging

项目1：衰老的起因和后果是虚弱和共病 摘要 在高度控制的实验室中，近亲交配动物的数据翻译存在着根本的差距 环境对生活在复杂环境中的遗传多样性人类的衰老经历的影响。 伴侣犬提供了独特的机会来检查具有不同基因和基因的队列中的衰老 环境背景、单独诊断和治疗的疾病以及广泛的 记录衰老和死亡原因的医学进展。这件事的首要目标是 U19研究计划是为了了解健康老龄化的遗传和环境决定因素 伴犬。作为实现这一目标的关键步骤，本项目旨在1)定义和标准化 基于共病、虚弱和慢性的犬衰老三个新轴的成分测量 炎症使用从人类群体转换的测量结果，这些测量结果可用于在 兽医全科医学；以及2)确定这三个新方面之间的关系，以及狗的存活率 和健康的衰老。为了实现这些目标，整整10,000只伴犬(纵向研究) )，它们的主人和兽医将被招募来收集狗的健康数据，包括 人口统计、病史、基本体格测量和兽医记录的诊断 记录，以及主人问卷中的人类生活方式和狗的护理。一群狗将被用来 开发和测试评估身体参数的新程序，包括步态速度和爬楼梯， 以及身体状况和肥胖的非标准测量。其他数据将在 选择800只狗的样本(Precision队列)，包括每年一次的体检(体重和 体型、身体状况评分、体温、脉搏、呼吸)、实验室分析(CBC、生化图谱和 尿液分析)、炎症状态以及认知和行动能力测量，以评估这三项 新的表型轴。将进行分析以测试已开发的暴露变量之间的关联 以及生存，包括脆弱等途径的结果。该项目对联合国环境规划署的总体使命至关重要 计划，并将与核心D和所有其他项目密切协同工作，以测试关于如何 健康衰老受环境(核心D)、基因(项目2)、分子生物标记物和 途径(项目3)和雷帕霉素治疗(项目4)。该项目不仅有可能提供 更好的方法来帮助兽医和主人保持狗的健康，同时也能识别独特的特征 狗的寿命和功能，这将是对人类种群转化的最大价值。

PROJECT 1: FRAILTY AND COMORBIDITY AS CAUSE AND CONSEQUENCE OF AGING ABSTRACT A fundamental gap exists in the translation of data from inbred animals in highly controlled laboratory environments to the experience of aging among genetically diverse humans living in complex environments. Companion dogs offer the unique opportunity to examine aging in a cohort that has differing genetic and environmental backgrounds, diseases that are individually diagnosed and treated, and extensive documentation of the medical progression through aging and causes of death. The overarching goal of this U19 Research Program is to understand the genetic and environmental determinants of healthy aging in companion dogs. As a critical step in achieving this goal, this Project aims to 1) define and standardize component measurements for three new axes of canine aging based on comorbidity, frailty and chronic inflammation using measurements translated from human populations that are feasible for measurement in a veterinary general practice; and 2) identify relationships among these three new aspects, and canine survival and healthy aging. To accomplish these goals, a full cohort of 10,000 companion dogs (the Longitudinal Study Population), their owners and veterinarians will be recruited to collect data on the dogs' health including demographics, medical history, basic physical measures and recorded diagnoses from veterinary medical records, as well as human lifestyle and dog care from owner questionnaires. A subset of dogs will be used to develop and test new procedures for assessing physical parameters, including gait speed and stair climbing, as well as non-standard measurements for body condition and obesity. Additional data will be collected on a select sample of 800 dogs (the Precision Cohort) to include an annual physical examination (body weight and size, body condition score, temperature, pulse, respiration), laboratory assays (CBC, biochemical profile and urine analysis), inflammatory status, and cognitive and mobility measurements needed to evaluate the three new phenotypic axes. Analyses will be conducted to test associations between developed exposure variables and survival including pathway outcomes such as frailty. This Project is critical to the overall mission of the Program, and will work in close synergy with Core D and all other Projects to test hypotheses regarding how healthy aging is influenced by the environment (Core D), genes (Project 2), molecular biomarkers and pathways (Project 3), and rapamycin treatment (Project 4). This Project has the potential not only to provide better methods to assist veterinarians and owners in keeping dogs healthy, but also to identify unique features of dog longevity and functionality that will be of the greatest value in translation to human populations.