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Thursday, 21 July 2016

The Dog Aging Project

Please welcome today's guest contributor, Dr. Silvan Urfer, a veterinarian with a background in population genetics. He is based at the University of Washington and currently working on the Dog Aging Project.

As a researcher working on the Dog Aging Project, I am glad to share some of our current work and results with the readers of this blog. Our project is based at the University of Washington in Seattle under the direction of Drs. Daniel Promislow and Matt Kaeberlein, and we are interested in studying aging in privately owned dogs – both descriptively and by testing interventions that we expect to increase healthy longevity in our four-legged friends. By following 10,000 companion dogs from homes throughout the United States over their lifetime, the Dog Aging Project aims to discover the genetic and environmental factors that determine whether a dog will live a long and healthy life. Moreover, through an intervention study we describe here, we will explore the potential to actually increase the likelihood that a dog will live a healthy long life. 

Meet Zeke, a canine citizen scientist in the Dog Aging Project
Aging is the single most important risk factor for a variety of diseases that affect both dogs and humans, such as cancer, heart disease, cognitive decline, arthritis, or kidney failure. Thus, addressing aging can be expected to result in a wide variety of potential health benefits: In fact, the potential benefits of targeting aging lead us to believe that this approach can be called “The Ultimate Preventive Medicine”, as it would have beneficial effects across the wide spectrum of otherwise unrelated diseases that share aging as their common risk factor.

Interestingly, the basic mechanisms of aging appear to be very similar across species, which has allowed scientists to identify risk factors and interventions in species with very short life spans, which can then be translated to longer-lived species. Thus far, this process has led from yeast through worms and flies to mice. We now argue that establishing the privately owned domestic dog as a model for human aging is the logical next step to take.

Dogs are a very interesting model in that they share our human environment, develop many of the same age-related diseases that we develop ourselves, and also receive comparable medical care, which we argue makes them an ideal model for aging in humans. In addition, the dog’s comparably shorter life span also means that it is better suited as a model for evaluating genetic and environmental risk factors as well as potentially beneficial interventions on healthy aging, seeing as the results will become apparent much more quickly than they would if such studies were to be performed in humans. With this in mind, our goal is to establish a generally accepted definition of what constitutes an aged dog, and then investigate the factors that contribute to that phenotype – be they genetic, epigenetic, metabolic, or environmental.

Apart from their usefulness as a model for human health, identifying interventions that have the potential to make our dogs live and stay healthy for longer would be a highly desirable goal all in itself, and there is also the aspect of keeping service and other working dogs healthy for longer, which has the potential to generate substantial financial savings.
Shadow, of the Dog Aging Project
One such potential intervention is a drug called rapamycin: It is the product of Streptomyces hygroscopicus, a bacterium that was originally discovered in the soil of Easter Island/Rapa Nui in the 70’s. Rapamycin has been FDA approved as an immune modulator since 1999 and has more recently been shown to increase longevity by 30% when given to mice that were biologically about as old as a 60-year-old human. We know that it achieves this effect by activating some of the same metabolic pathways that are activated by eating a low calorie diet, and we also know that feeding dogs a low calorie diet makes them live and stay healthy for longer. Based on this, it follows that giving rapamycin to dogs could be an interesting and potentially very valuable intervention to increase healthy lifespan in our dogs.

We recently completed a double-blind placebo-controlled pilot study on 24 privately owned middle-aged medium size dogs that received either rapamycin or placebo for 10 weeks. This being a pilot study, our main goal was to make sure there were no side effects at the doses we used. In addition to clinical evaluation, we also did bloodwork before, during and after the study, as well as heart ultrasound before and after because rapamycin has been reported to have positive effects on heart function in aging mice.

The results are now in, and we are pleased to report that rapamycin did not cause any clinical side effects in our study population at the doses we used. The bloodwork showed some changes that may indicate longer red blood cell survival and some changes in metabolism, but all blood parameters remained within normal limits in our population.

However, the most interesting part of our results – especially considering our relatively small sample size – is that rapamycin seems to have significant beneficial effects on heart function. Even more interestingly, those beneficial effects seem to be highly specific to the measures of heart function that we know are deteriorating with age, and they seem to apply to both the contraction (systole) and the relaxation (diastole) phases of heart function (Fractional Shortening and E/A Ratio). In short, rapamycin seems to be able to reverse some of the changes that are characteristic of an aging heart when given to dogs for 10 weeks, which is certainly encouraging within the context of improving healthy aging in our dogs.

We are currently seeking funding for a larger, longer term trial of rapamycin in privately owned dogs, which will allow us to determine whether it has a beneficial effect on life expectancy and healthy aging in them. We predict that rapamycin will not only allow the dogs to live longer, but will reduce their risk for several types of cancer, cognitive decline, kidney disease, and other age-associated disorders. For this study, we are planning to recruit several hundred dogs to study over a period of several years, which will allow us to collect more extensive data on health and mortality. More information on the project and how you can help can be found at our web site at http://dogagingproject.com

Dog Aging Project
University of Washington Medicine Pathology
1959 NE Pacific Street
Box 357705
Seattle, WA 98195
Waiting Wolfhounds. Credit: Silvan Urfer
Further Reading