Project 4: Determining the ability of rapamycin to improve lifespan and healthspan in companion dogs

项目4：增强雷帕霉素改善生命周期和健康的能力 在伴侣犬中 摘要 老年科学的一个主要目标是通过基本的和可持续的健康教育， 对衰老生物学的转化研究虽然在了解这些问题方面取得了重大进展， 衰老的基本机制，并在实验室模型中开发干预措施以延缓衰老，迄今为止， 这些发现在临床环境中的应用有限。该项目旨在迈出第一步， 通过测试雷帕霉素治疗是否可以延长寿命并改善 健康寿命的伴侣（宠物）狗，类似于在实验室小鼠中观察到的。这将是 通过一项双盲、安慰剂对照的兽医临床试验完成，该试验涉及300名健康、中等年龄、 老年（至少6岁）、较大（至少18 kg）的伴侣犬。将犬随机分配至 安慰剂、短暂（6个月）或连续（3年）治疗组以及雷帕霉素对生存率的影响 以及衰老期间的整体健康状况进行评估。健康措施将包括对行动能力的评估， 脆弱性和疾病发生率（与项目1合作）。此外，鉴于报告的有益效果， 雷帕霉素治疗对老年小鼠心脏和认知功能的影响，将特别强调 评估雷帕霉素对狗的认知功能（用核心C）和心脏功能的影响。在 与项目3合作，雷帕霉素治疗对全身代谢和肠道的影响， 伴侣犬的微生物组将通过血清代谢组学和细菌代谢分析进行评估。 粪便样品的组成。总的来说，这项研究将促进我们对相互作用的理解， mTOR信号传导和生活在人类环境中的狗的基本衰老过程之间的关系， 潜在地延长狗的健康寿命和寿命，从而改善狗及其 业主

PROJECT 4: DETERMINING THE ABILITY OF RAPAMYCIN TO IMPROVE LIFESPAN AND HEALTHSPAN IN COMPANION DOGS ABSTRACT A primary goal of geroscience is to improve health, longevity, and quality of life for people through basic and translational research into the biology of aging. While there has been significant progress in understanding the basic mechanisms of aging and developing interventions to delay aging in laboratory models, to date there has been limited application of these findings in a clinical setting. This project aims to take a first step toward such translational application by testing whether treatment with rapamycin can increase lifespan and improve healthspan in companion (pet) dogs, similar to what has been observed in laboratory mice. This will be accomplished through a double-blind, placebo-controlled veterinary clinical trial involving 300 healthy, middle- aged (at least 6 years old), larger (at least 18 kg) companion dogs. Dogs will be randomized into either placebo, transient (6 months) or continuous (3 years) treatment groups and the effect of rapamycin on survival and overall health during aging will be assessed. Measures of health will include assessments of mobility, frailty, and disease incidence (in collaboration with Project 1). In addition, given the reported beneficial effects of rapamycin treatment on cardiac and cognitive function in older mice, there will be a special emphasis on assessing the effects of rapamycin on cognitive function (with Core C) and cardiac function in dogs. In collaboration with Project 3, the effects of rapamycin treatment on systemic metabolism and the intestinal microbiome in companion dogs will be assessed through serum metabolomics and analysis of bacterial composition of fecal samples, respectively. Overall, this study will advance our understanding of the interaction between mTOR signaling and basic aging processes in dogs living in the human environment and could potentially extend the healthspan and lifespan of dogs, thus improving the quality of life for both dogs and their owners.