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

项目1：衰老的原因和后果-虚弱和多病 摘要 在高度受控的实验室中， 在复杂的环境中生活的基因多样的人类之间的老化经验。 伴侣狗提供了独特的机会，以检查老化的队列，有不同的遗传和 环境背景，个别诊断和治疗的疾病， 通过衰老和死亡原因记录医学进展。这个项目的首要目标是 U19研究计划旨在了解健康老龄化的遗传和环境决定因素， 伴侣犬作为实现这一目标的关键一步，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分量测量 使用从人群中翻译的测量结果，这些测量结果可用于 兽医一般实践; 2）确定这三个新方面之间的关系，以及犬的生存 和健康的衰老。为了实现这些目标，一个完整的队列的10,000伴侣狗（纵向研究 他们的主人和兽医将被招募来收集狗的健康数据，包括 人口统计学、病史、基本身体测量和兽医诊断记录 记录，以及人类的生活方式和狗的照顾从业主问卷。一部分犬将用于 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（精确队列），包括年度体检（体重和 大小、身体状况评分、体温、脉搏、呼吸）、实验室测定（CBC、生化特征和 尿液分析），炎症状态，以及认知和移动性测量，以评估这三个 新的表型轴。将进行分析，以检验已开发的暴露变量之间的关联 和存活率，包括路径结果，如虚弱。该项目对整个使命至关重要， 计划，并将与核心D和所有其他项目密切协作，以测试有关如何 健康老龄化受环境（核心D），基因（项目2），分子生物标志物和 途径（项目3）和雷帕霉素治疗（项目4）。该项目不仅可以提供 更好的方法来帮助兽医和主人保持狗的健康，但也要确定独特的功能， 狗的寿命和功能，这将是最大的价值，在翻译给人类。

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.