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一项随机对照试验,旨在确定短期雷帕霉素治疗对 24 只中年伴侣犬的影响。

A randomized controlled trial to establish effects of short-term rapamycin treatment in 24 middle-aged companion dogs.

机构信息

Department of Pathology, University of Washington, Seattle, WA, USA.

Dog Aging Project, Seattle, WA, USA.

出版信息

Geroscience. 2017 Apr;39(2):117-127. doi: 10.1007/s11357-017-9972-z. Epub 2017 Apr 3.

Abstract

Age is the single greatest risk factor for most causes of morbidity and mortality in humans and their companion animals. As opposed to other model organisms used to study aging, dogs share the human environment, are subject to similar risk factors, receive comparable medical care, and develop many of the same age-related diseases humans do. In this study, 24 middle-aged healthy dogs received either placebo or a non-immunosuppressive dose of rapamycin for 10 weeks. All dogs received clinical and hematological exams before, during, and after the trial and echocardiography before and after the trial. Our results showed no clinical side effects in the rapamycin-treated group compared to dogs receiving the placebo. Echocardiography suggested improvement in both diastolic and systolic age-related measures of heart function (E/A ratio, fractional shortening, and ejection fraction) in the rapamycin-treated dogs. Hematological values remained within the normal range for all parameters studied; however, the mean corpuscular volume (MCV) was decreased in rapamycin-treated dogs. Based on these results, we will test rapamycin on a larger dog cohort for a longer period of time in order to validate its effects on cardiac function and to determine whether it can significantly improve healthspan and reduce mortality in companion dogs.

摘要

年龄是人类及其伴侣动物大多数发病和死亡原因的最大单一风险因素。与用于研究衰老的其他模式生物不同,狗生活在人类环境中,面临着相似的风险因素,接受着相似的医疗护理,并患上许多与人类相同的与年龄相关的疾病。在这项研究中,24 只中年健康犬接受了安慰剂或非免疫抑制剂量的雷帕霉素治疗 10 周。所有犬在试验前、试验期间和试验后均接受了临床和血液学检查,并在试验前后进行了超声心动图检查。与接受安慰剂的犬相比,雷帕霉素治疗组没有出现临床副作用。超声心动图显示,雷帕霉素治疗犬的舒张和收缩与年龄相关的心脏功能指标(E/A 比值、缩短分数和射血分数)均有所改善。所有研究参数的血液学值均在正常范围内;然而,雷帕霉素治疗犬的平均红细胞体积(MCV)降低。基于这些结果,我们将在更大的犬群中进行更长时间的雷帕霉素测试,以验证其对心脏功能的影响,并确定它是否能显著延长伴侣犬的健康寿命并降低其死亡率。

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