title: 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.
authors.affiliation: Department of Pathology, University of Washington, Seattle, WA, USA.|Dog Aging Project, Seattle, WA, USA.
authors.forename: Silvan R
authors.initials: SR
authors.lastname: Urfer
authors.affiliation: Department of Pathology, University of Washington, Seattle, WA, USA.|Dog Aging Project, Seattle, WA, USA.
authors.forename: Tammi L
authors.initials: TL
authors.lastname: Kaeberlein
authors.affiliation: Dog Aging Project, Seattle, WA, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Mailheau
authors.affiliation: VCA Clinical Studies, Los Angeles, CA, USA.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Bergman
authors.affiliation: Dog Aging Project, Seattle, WA, USA.|College of Veterinary Medicine, Texas A&M University, College Station, TX, USA.
authors.forename: Kate E
authors.initials: KE
authors.lastname: Creevy
authors.affiliation: Department of Pathology, University of Washington, Seattle, WA, USA.|Dog Aging Project, Seattle, WA, USA.|Department of Biology, University of Washington, Seattle, WA, USA.
authors.forename: Daniel E L
authors.initials: DEL
authors.lastname: Promislow
authors.affiliation: Department of Pathology, University of Washington, Seattle, WA, USA. kaeber@uw.edu.|Dog Aging Project, Seattle, WA, USA. kaeber@uw.edu.
authors.forename: Matt
authors.identifier: 0000-0002-1311-3421
authors.initials: M
authors.lastname: Kaeberlein
mesh_terms: D000375:Aging / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004285:Dogs; D004334:Drug Administration Schedule / Q000662:veterinary; D005260:Female; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008297:Male; D057805:Pets; D020123:Sirolimus / Q000008:administration & dosage*; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology
chemical_list: D007166:Immunosuppressive Agents; D020123:Sirolimus
keywords: Blood chemistry; Cardiac aging; Dogs; Echocardiogram; Healthspan; Rapamycin; Sirolimus