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

项目4：测定雷帕霉素延长寿命和健康寿命的能力 在伴犬中 摘要 老年科学的一个主要目标是通过基本的和 对衰老生物学的翻译研究。虽然在理解 衰老的基本机制和在实验室模型中开发延缓衰老的干预措施，到目前为止已经有 这些发现在临床环境中的应用受到了限制。该项目旨在向这样的目标迈出第一步 通过测试雷帕霉素治疗是否可以延长寿命和改善情况进行翻译应用 伴侣(宠物)狗的健康寿命，与在实验室小鼠身上观察到的相似。这将是 通过一项双盲、安慰剂对照的兽医临床试验完成，涉及300名健康、中等和 年龄较大(至少6岁)、体型较大(至少18公斤)的伴侣犬。狗将被随机分成两组 安慰剂、暂时性(6个月)或持续(3年)治疗组以及雷帕霉素对生存率的影响 并将评估老龄化期间的整体健康状况。健康衡量标准将包括对行动能力的评估， 脆弱性和疾病发病率(与项目1合作)。此外，鉴于已报道的有益效果 关于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(核心C)和心脏功能的影响。在……里面 与项目3合作，雷帕霉素治疗对全身代谢和肠道的影响 将通过血清代谢组学和细菌分析来评估伴犬的微生物群 粪便样本的成分。总体而言，这项研究将促进我们对互动的理解 在生活在人类环境中的狗的mTOR信号和基本衰老过程之间，可能 有可能延长狗的健康和寿命，从而提高狗和狗的生活质量 主人。

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.