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

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.

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Acknowledgements

We would like to thank Dr. Karen Kline and Dr. Heidi MacLean for clinical veterinary support. This work was partially supported by the University of Washington Nathan Shock Center of Excellence in the Basic Biology of Aging (NIH Grant P30AG013280). SU was supported by donations from the Irish Wolfhound Association of New England and the Donner Foundation to the Dog Aging Project. DP and KC received support from NIH Grant R24AG044284.

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Correspondence to Matt Kaeberlein.

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All procedures were approved by the University of Washington Institutional Animal Care and Use Committee (IACUC) under protocol number 4359-02. All of the owners completed a written informed consent prior to their first study-related veterinary visit.

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Urfer, S.R., Kaeberlein, T.L., Mailheau, S. et al. A randomized controlled trial to establish effects of short-term rapamycin treatment in 24 middle-aged companion dogs. GeroScience 39, 117–127 (2017). https://doi.org/10.1007/s11357-017-9972-z

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Keywords

  • Dogs
  • Cardiac aging
  • Rapamycin
  • Echocardiogram
  • Blood chemistry
  • Healthspan
  • Sirolimus