A longitudinal study that aims to determine the biological, lifestyle, and environmental factors that influence healthy aging in dogs, the Dog Aging Project is expected to spearhead advances in veterinary clinical practice.
“Should I change my dog’s food?” “What about probiotics?” “What can I give my dog for her coat?” As veterinary professionals, we are often asked for advice about diet, supplements, exercise regimes, and other factors that influence overall health. Veterinary medicine is quite robust when it comes to diagnosing and treating illness, but when it comes to proactive maintenance of ideal health, there is a distinct lack of evidence-based research upon which to base our recommendations. The research currently underway at the Dog Aging Project intends to close that gap.
The Dog Aging Project is an innovative initiative that brings together a community of dogs, dog owners, veterinarians, researchers and volunteers to carry out the most ambitious study of dog health in the world. Funded by a U19 grant from the National Institute on Aging, a part of the National Institutes of Health, the Dog Aging Project is a longitudinal study modeled after ongoing human longitudinal studies such as the Framingham Heart Study and the Baltimore Longitudinal Study of Aging. The Dog Aging Project has three primary research aims: define aging, explain aging, and intervene in aging.
Why study aging?
In a clinical setting, veterinary professionals often treat patients with chronic disease and multiple comorbidities. While there are tools to diagnose and treat many of these conditions, prevention would be the gold standard and is a key focus of integrative approaches to veterinary medicine. In humans, the single greatest risk factor for the development of many of these diseases, including the major causes of mortality in developed nations, is aging.1 This is likely true for dogs as well. T
he Dog Aging Project is focused on understanding how biology, lifestyle and environment interact to influence healthy aging, with the goal of intervening to increase healthspan — the period of life spent free of disease. Ultimately, healthy aging requires the maintenance of independent physical function, cognitive ability, mental health, and general well-being.2
Why study dogs?
Geroscience has made huge advances in the last few decades, but most of these studies have been conducted in laboratory settings with short-lived model organisms such as yeast, fruit flies, nematodes and mice. Several studies of health and aging have been conducted in companion dogs by researchers in our group and elsewhere,3,4,5,6 but only the Golden Retriever Lifetime Study (GRLS) combined a large-scale longitudinal study with clinical and genetic data for each dog.7
The Dog Aging Project is working closely with, and expanding on, the breed-specific work by GRLS. By enrolling tens of thousands of both purebred and mixed breed dogs, the dataset we are building will encompass the full range of canine genetic and phenotypic diversity, including variation in size, shape, behavior, life expectancy, and age-related disease.8 Not only does this research have the potential to directly advance canine health; it also has the potential to inform human medical research as well.
A novel veterinary research framework
The Dog Aging Project is a citizen science endeavor, which depends on the active participation of dog owners who both nominate their dogs for the project and collect data on their dogs throughout their lifetimes. All dogs are welcome — young and old, purebred and mixed breed, intact and sterilized, healthy dogs and those with chronic illnesses. Currently, dog owners from all around the US, and from a range of socioeconomic and cultural backgrounds, have nominated their dogs for the project.
Our participants are invited to establish a secure personal portal at the Dog Aging Project and complete the Health and Life Experience Survey, an extensive questionnaire that collects detailed information about each dog’s lifestyle, home environment, and health history. Using a sophisticated cohort design, subsets of dog owners will be invited to participate in other activities as detailed below.
The massive dataset generated by the Dog Aging Project will be made available to researchers around the world in a privacy-protected, open data model in order to maximize the project’s impact on the advancement of dog health. This complex project is supported by a highly interdisciplinary team from research institutions around the world who have partnered with veterinary teaching hospitals across the US. This collaboration will enable the Dog Aging Project to meet its three primary research aims.
Defining aging in dogs
In humans, standardized clinical metrics quantify aging; for example, the Grip Test or Chair Stand. These are largely absent in veterinary medicine. Both dog owners and their veterinary health team members know that some dogs seem to age more healthfully than others. Some 12-year-old dogs play like puppies, while others experience the phenomenon of “frailty,” displaying reduced energy, declining cognition, and limited mobility. Unlike human medicine, there are no clearly defined metrics to determine how well or how poorly a dog is aging.
In order to define aging in dogs, the Dog Aging Project is developing a rigorous, reproducible and practical Canine Fragility Score, which will be based on familiar tools and measurements (body weight, body condition score, activity monitor collars), existing scoring systems (Canine Cognitive Dysfunction Rating Score,9 Health-Related Quality of Life Instrument10) and novel metrics (gait speed and stair climb). Given the extreme variation in size, activity level, temperament, environment, and disease susceptibilities among dogs, the key to defining aging will involve measuring the change in an individual’s metrics over time, hence the value of a long-term study like the Dog Aging Project.
In addition, researchers in our group are documenting and describing the multimorbidity states of companion dogs.11,12 We will use this data to predict the likelihood that an aging dog with one diagnosis will develop a second within a given timespan. These data will be used to develop a Canine Multimorbidity Index to be used in the clinical management of aging dogs. Both this index and the Canine Fragility Score will be made available to clinicians to be used as a benchmark of canine health and to indicate the most valuable targets for intervention.
Explaining aging in dogs
This research aim will be accomplished by discovering the genetic and environmental factors that influence aging and by identifying intermediate molecular traits through which their influence unfolds. Ten thousand dogs will be selected from among all Dog Aging Project participants to receive a saliva swab kit. This kit will be utilized to capture genomic information about these dogs. Our team will integrate health measures and behavioral traits with genome sequence data and carry out comprehensive genome-wide association studies.
In addition, 1,500 participants from whom we have collected genomic information will partner with their primary care veterinarians to provide blood and fecal samples. The team at the Dog Aging Project will use a systems biology approach to quantify the metabolome (total number of metabolites), the microbiome (gut microfauna), and the epigenome (chemical compounds and proteins that regulate transcription) in this subset of dogs. Our team will use the data to identify molecular biological predictors of disease and longevity, and develop an epigenetic clock that predicts biological age in dogs.
80,000 dogs and counting
Response to the official launch of the Dog Aging Project in November 2019 has been astounding. As of January 2020, over 80,000 dog owners have nominated their dogs for this research. Data collection has already begun. This comprehensive multimodal approach will allow us to determine the biological, lifestyle, and environmental factors that influence healthy aging in dogs, which we are confident will lead to advances in veterinary clinical practice and pave the way for advances in human geroscience as well.
For more information, visit dogagingproject.org.
References
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11Hoffman J, et al. “The companion dog as a model for human aging and mortality”. Aging Cell. 2018.
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13Halloran J, et al. “Chronic inhibition of mammalian target of rapamycin by rapamycin modulates cognitive and non-cognitive components of behavior throughout lifespan in mice”. Neuroscience. 2012; 223:102-113.
14Miller RA, et al. “Rapamycin-mediated lifespan increase in mice is dose and sex dependent and metabolically distinct from dietary restriction”. Aging Cell. 2014;13(3):468-477.
15Urfer SR, et al. “A randomized controlled trial to establish effects of short-term rapamycin treatment in 24 middle-aged companion dogs”. Geroscience. 2017; 39(2):117-127.
