**SPOTLIGHT** The Dog Aging Project: Rockin' Awesome Research for Rover

The largest, dog-centric, longitudinal, non-invasive research project in the world is going on in our backyard at the University of Washington in Seattle. This incredible study is being overseen by the UW alongside Texas A & M University. Thousands of veterinarians will also take part in the project. The Dog Aging Project is a Citizen Science project, and all of the data will be available as an open resource (while ensuring the privacy of the participants). In other words, citizens, scholars, and researchers from around the world can review and use the data collected.

The largest, dog-centric, longitudinal, non-invasive research project in the world is going on in our backyard at the University of Washington in Seattle.

Dogs are unique in that they have been bred over thousands of years to be integral members of our lives. As we study dogs, we learn about dogs, but we also, in turn, study ourselves. The National Institute on Aging funded The Dog Aging Project with this in mind. When it comes down to it dog genes and human genes are surprisingly similar. (We already knew that didn’t we? Dogs are family!) This combined with the fact that dogs reside with us and are running, playing, and sleeping in the same environments as we are makes them the perfect partners in gaining insight into both dog health and human health.

Photo @SeattlePupMagazine

The Dog Aging Project understands that by monitoring dogs and what they do with their lives over time we can learn more about our precious furry family members; the researchers hope to use this information to help veterinarians care for dogs as they age. Through consistent monitoring of canines over their lifespans (upwards of 17-20 years) researchers are hopeful that they will find ways to help improve dog health, well-being, and maybe even help discover ways for dogs to live longer healthier lives!

Dogs are unique in that they have been bred over thousands of years to be integral members of our lives.

The Dog Aging Project overseen by Professor Daniel Promislow and Professor Matt Kaeberline, Department of Pathology, University of Washington School of Medicine; and Associate Professor and veterinarian Dr. Kate Creevy, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University will be monitoring 10,000 canines from across all 50 states. Over the course of these precious pups’ lives, UW researchers—alongside researchers and veterinarians from around the country—will collect hundreds of thousands of points of data.

In addition to monitoring the dogs’ daily habits (think Fitbits for dogs), owners will be texted questions like “did you give your dog a treat today?” in addition to filling out questionnaires with questions ranging from what kind of indoor flooring your family has and how often your dog goes for a walk, to what kind of food and treats you feed your dogs.. All of the dog-life experience data collected will be combined with the pup’s medical records and Federal, State, and Local publicly available data including: water and air quality reports, city sizes and amount of green space, population, and more. The main goal of the project, 95%, will be the gathering of long-term information from dogs and their owners. By watching how animals (big and small) age we can determine what may affect our dogs’ lives and well-being. The folks at the Dog Aging Project like to call this “The power of paying attention."

Over the course of these precious pups’ lives,

UW researchers—alongside researchers and veterinarians from around the country—will collect hundreds of thousands of points of data.

The overall Dog Aging Project "pack" of 10,000 dogs will have their genomes sequenced. Within that group of 10,000, there will be two smaller subgroups (what researchers call “cohorts”) where additional information will be gathered. The first subgroup will include 1,500 dogs and owners who have agreed to supply their pups’ biological samples through their veterinarian. Fecal matter samples will be collected alongside blood, hair and nail samples. Blood will be used to measure the metabolome (all the small molecules in the blood) and the epigenome (a measure of whether genes are turned on or off); fecal samples will be used to measure the microbiome. Each one of these 1,500 dogs will have this information monitored over their lifespans. The second subgroup (cohort) will consist of 500 dogs who will participate in a clinical drug research trial that will be monitoring the dogs to test the hypothesis "does a specific drug has a positive effect on dog health and longevity?"

Microbiome

Fecal samples (get your poop bags ready!) can provide a slew of information about a dog’s life and physical health. The microbiome (the bacteria, viruses, archaea (one-celled organisms), and fungus that live in the intestines) has been the topic of a lot of research lately. Healthy microbiomes have been linked to increased mental capacity, and fecal transplantation has been the subject of research as well. By replacing the microbiome, doctors can improve the body’s responses to some infections.[1]

DNA/The Body’s “Code”

Dogs also have another interesting thing that makes them unique. Within their DNA they exhibit a gene that is thought to be responsible for a dog’s size. The ancestral version of this gene, which is the version found in wolves, is associated with large size. The novel form, which arose sometime during the evolution of domestic dogs, is common in small breed dogs. The gene explains about half the variation in size among dogs. The rest of the variation is due to other genes, and to environmental factors. Interestingly, small breed dogs also tend to be long lived. It is possible that this has something to do with IGF1, as the gene has been shown to be associated with longevity in mice, and possibly in humans as well. However, we do not yet have strong evidence that IGF1 is the reason that small dogs tend to live longer than large ones.

The IGF1 gene, that IGF-1 is an important regulator of growth. The IGF1 gene also happens to be located on the area of the DNA that is related to a dog’s size.[2]

Do the scientists know whether this gene is responsible for a dog’s life span? No, they don’t. But they sure do want to find out!

Through carefully analyzing and preserving blood and saliva samples, the researchers will collect data on each dog’s specific DNA and determine whether or not they fall into the ancestral or the novel category. Through consistent monitoring of the dogs’ health and well being over

the course of their lives the necessary data will accumulate and help answer whether or not there is a gene responsible for a dog’s life span.

The goal is that after this project is complete scientists will have a better idea of how to predict and improve dog health and longevity. The research teams will also monitor the dog’s genetic material over time. With age our code (DNA and what is known as the epigenome changes). These changes will be documented for these 10,000 dogs and provide a plethora of research on the internal milieu of these canines. At the end of these precious pups’ lives their veterinarians will perform necropsies to help determine what caused the death. Detailed records and samples from these procedures are essential and will be documented and preserved alongside the other biological samples that will be collected throughout the study.

"Safety is our #1 value. Nothing will be done that will endanger these dogs. We will be collecting only that that what would normally be collected during a routine visit to your veterinarian. No operations of any kind will be taking place.” --Professor Daniel Daniel Promislow, Pathology Department, UW School of Medicine

TRIAD (Test of Rapamycin in Aging Dogs)

The IGF2 gene, is also a major player in the second subgroup of this study, also known as “TRIAD.” TRIAD stands for “Test of Rapamycin in Aging Dogs.” Rapamycin (also known as Sirolimus) is a drug that historically has been used to prevent rejections of organ transplants and has been shown to suppress the immune system. It has also been linked to increasing longevity in yeast, flies, worms, and mice.[3] Adding Rapamycin to the diet of these animals has improved heart function (left-ventricle function in particular) and is shown to increase the body’s ability to pump blood effectively. As we (and our pups) age this ability decreases. When researchers gave Rapamycin to mice, this ability to pump blood went up, and the mice started to look and act younger.

Photo by @lifeasavoyager

The TRIAD study is an official clinical trial and will be conducted as one would a human trial. Owners who agree to be part of the study will have Rapamycin prescribed for their pup and will continue to give the medication for three years. The goal of this clinical trial is to find out if Rapamycin improves heart function within three years of treatment.

Researchers don’t know if Rapamycin will improve heart function/longevity in dogs, and they don’t think it will do anything bad, but they are doing the study to find out. Please note that Rapamycin can only be prescribed by veterinarians who are part of the study. The UW cannot legally provide this drug to owners. TRIAD is the smallest group of dogs in the study (3.5%) of the whole study. Dogs on Rapamycin will be on the drug for 3 years and then monitored for the rest of their lives (like the other dogs in the study).

The Dog Aging Project is an enormous endeavor which has brought together veterinarians and researchers from across the United States. From the administrative crew (public relations, communication) and the information technology data collection infrastructure team, to the bio bank, numerous researchers, and thousands of veterinarians this project is sure to make a splash! Universities include: University of Washington (research/IT infrastructure), Texas A & M (veterinarian communication, sample kits), Cornell University (Bio bank).

Material from this study will be shared in an Open Source/Citizen Science manner allowing researchers from around the world the opportunity to use the statistics. This, in turn, will provide a hub of canine health information and will form the foundation for additional dog-centric research in the future.

According to Dr. Daniel Promislow,


"there are many other disciplines that have expressed an interest in our data, it isn’t just about the sciences, many other departments, for example the department of philosophy has reached out with the hopes of tapping our research. It is very exciting."

Professor Daniel Promislow & Frisbee (above)

with Dubs (UW Mascot)

Photos courtesy of Daniel Promislow

The researchers are hoping to gather more funding and up the number of canine participants to 100,000. The search for dogs starts later this fall. Would you like to be part of the project?

There are 2 ways you can participate:

Nominate your pup! (1) The study will include all ages, all breeds (mixed and pure bred), all sexes (male, female, neutered, spade) from all 50 states. At this time the study is not reaching outside the United States but researchers hope that other researchers from around the world will reach out to collaborate on future projects. The more nominations there are the more likely it is that the researchers can collect a diverse group of subjects to study. The more diverse the study the more information they can gather!

To nominate your pup you must:

  • know the age of your dog down to the year. (Dogs will be monitored for the rest of their lives and it is very important to have this information.)

  • routinely take your pup to your veterinarian.

  • have a veterinarian who is set up with electronic vet medical records

  • Only one dog per household can be nominated.

(2) Another great way to be part of the project is to donate money to the study keep it going! Every little bit counts. As a community science open source study this information belongs to all of us.

WE can MAKE a DIFFERENCE in our DOGS LIVES by DONATING! Visit the Dog Aging Project website! https://dogagingproject.org/

Notes:

All photos (unless otherwise noted) are by Seattle Pup Magazine.

[1] For more on microbiome studies see, Louis Stone, “Fecal microbiota transplantation for Clostridioides difficile infection,” Nature June 17, 2019; and Megan Clapp, et. al., “Gut Microbiota’s Effect on Mental Health: The Gut-Brain Axis,” Clinics and Practice, 2017.

[2] JR Minkel, “What Makes Small Dogs Small?Scientific American, 2007.

[3] Interview with Dr. Daniel Promislow, Pathology Department, University of Washington School of Medicine, October 9, 2019. For more info on fruit flies and Rapamycin see, Joseph M. Schinaman, et.al., “Rapamycin Modulates Tissue Aging and Lifespan Independently of the Gut Microbiota in DrosophilaNature, 2019. For mice see, Alessandro Bitto, et.al., “Transient Rapamycin Treatment Can Increase Lifespan and Healthspan in Middle-Aged MiceELife, 2016.

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