Research on aging a natural fit for One Health approach
Research on aging a natural fit for One Health approach
Similarities between senior dogs and humans with Alzheimer's proving valuable for translational research
Updated January 3, 2024
Getting old is not for the weak, which is true not only for humans, but also dogs. They often share similar medical conditions as they age.
For example, approximately 1 in 4 dogs will, at some stage in their life, develop neoplasia, with almost half of dogs over the age of 10 developing cancer. Meanwhile, cancer is the second most common cause of death in people in the U.S., after heart disease.
Canine cognitive decline (CCD) is present in 28% of dogs aged 11 to 12 years, with a prevalence that increases to 68% around 15 to 16 years old. CCD mirrors many of the physiological and behavioral changes observed in humans with dementia and Alzheimer's disease (AD), including disorientation, memory problems, changes in activity levels, and pathologies, such as brain atrophy. AD is the seventh leading cause of death in humans.
With today’s technological advancements, researchers are calling for a concerted effort to gather big data on aging dogs in the hopes of benefitting not only veterinary care, but also to inform human medicine.
Launched in 2012, the primary goal of the latter is to identify nutritional, environmental, lifestyle, and genetic risk factors for cancer and other diseases in Golden Retrievers. One major finding from the study’s data is that hemangiosarcoma (HSA) appears to be the leading cause of cancer deaths. For all enrolled dog to date, 75% of deaths are cancer-related; of those cancer deaths, almost 70% are HSA.
In response, the Foundation launched its Hemangiosarcoma Initiative this year, which dedicates funding and resources to advance the prevention, detection and treatment of, and potentially cures for, this cancer in dogs.
A study that appeared in PLoS One in March 2020, suggested that HSA, a metastatic disease that progresses rapidly despite chemotherapy, shares genetic similarities with angiosarcoma (AS) in humans. Because it is rare and has limited treatment options and a poor survival rate, developing therapies has been difficult; however, HSA in dogs could serve as a model to test experimental therapies in clinical trials.
The initial group of 3,044 dogs in the Golden Retriever Lifetime Study has now decreased to 1,653, but prospective data and samples are available to researchers by request and at no charge, to help spur more studies seeking to address canine cancer and other health challenges in dogs.
For example, beginning in March 2021, an additional questionnaire was offered to participants specifically focused on CCD. Its questions address behaviors related to learning and memory, disorientation, social interactions, sleep-wake cycles, house soiling, activity, and anxiety. By collecting these data, MAF and the Purina Institute are working to improve understanding of incidence, prevalence, and risk factors.
The MAF is also partnering with Dr. John Fryer of the Mayo Clinic in Arizona to study CCD by evaluating donated brain tissue from study dogs that have died.
“The data they find on microscopic examination of these tissues will be compared to the behavior data collected to see if there is a correlation between observed brain abnormalities and behavior abnormalities,” said Dr. Kelly Diehl, senior director of science communications at MAF. “Our hope is that more researchers will use our data and samples to answer other questions associated with aging.”
Dogs and dementias
Canine cognitive disorder shares similarities with human dementia, including a substantial vascular component, says Dr. Atticus Hainsworth, a neuroscientist based at St. George’s, University of London. His research focuses on vascular contributions to cognitive impairment and dementia (VCID).
One study, published in the journal Stroke in June 2016, looked at animal models and which ones had the best potential to increase understanding of specific vessel pathologies, how these pathologies cause parenchymal lesions, how risk factors influence vessel and parenchymal lesion changes, and the mechanisms that link them all to VCID.
When it comes to how aging dogs might be used as models for human diseases, “We are just beginning to find that out,” he said. “They are clever animals, with a large brain, good memory, and complex behaviors. Like humans, they have extensive white matter,” and have longer lifespans than some other animal models.
Based on his laboratory research, he performed a clinical trial in older people with small vessel disease. He wanted to know if the widely prescribed drug tadalafil had beneficial brain effects. The trial wasn’t successful, but it suggested additional, follow-up experiments that would be sensible to do.
“The message from studies in humans is that physical exercise, even into late life, is the best strategy for dementia prevention,” he said.
According to Dr. Hainsworth, the future of translation research looks, “really exciting, and larger animal species, including dogs, will be a big part of that.”
No shortage of aging dogs
Dr. Joel Ehrenzweig is another researcher looking at the connection between disease in aging dogs and that in humans. He was in private practice for 25 years before founding Veterinary Health Research Centers, a contract research organization. He said given the fact that dogs are living longer than they did 20 or 30 years ago, they’re going to be experiencing cognitive decline for longer.
Reports of his recent studies including one he co-authored with Dr. Robert P. Hunter in the November 2023 issue of AJVR, and another as lead author in the same month's issue of JAVMA, highlight the importance of using client-owned animals with naturally occurring CCD as disease-relevant surrogates for translational AD research.
In one of the reports, Dr. Ehrenzweig and his fellow authors introduced the Dogs Overcoming Geriatric Memory and Aging (DOGMA) initiative. They called for a study to be conducted in veterinary practices that would analyze the relationship between blood biomarkers and biometric behavior in older dogs to establish benchmark CCD data.
“The fact that we now have wearable technology (collars) that can very accurately record and track movements of animals makes potential clinical signs, on the behavioral side, easier to find,” Dr. Ehrenzweig said.
The neurodegenerative decline in dogs starts years before clinical signs are evident, he explained. With the help of wearable technology, it’s possible to pair up physical observations with blood biomarkers to see if and when a particular dog is on the cusp of neurodegenerative decline.
Once an affected dog is identified, Dr. Ehrenzweig and others with the DOGMA initiative can reach out to veterinary and human medical researchers, with the dog owner’s permission, to discuss the possible use of early interventions for CCD.
“The ability for practitioners … we are empowering them to not only help themselves and their practices but really do something very significant in the realm of One Health and medical care for populations with four legs and two,” Dr. Ehrenzweig said.
A version of this story appears in the March 2024 print issue of JAVMA
Better end-of-life information for pets could help researchers, veterinarians
The Dog Aging Project (DAP), funded by the National Institute on Aging, has enrolled more than 45,000 dogs since it started in 2019.
Taking a page from human medicine, DAP researchers—which included veterinary health professionals and human gerontology experts—created an End of Life Survey (EOLS) to gather owner-reported mortality data about companion dogs.
“Before factors that influence healthy life span can be discovered, aging studies must first obtain the end points necessary to make meaningful conclusions,” the authors wrote in a study published in the September 2023 issue of JAVMA. “To accurately capture this mortality data in humans, studies must contend with underreported or incorrectly reported information on cause of death and/or manner of death when individuals die at home, when death certificates are improperly completed, when individuals have several comorbidities at the time of death, and when autopsies are not performed. Veterinary studies investigating the cause and manner of death in companion dogs face similar obstacles as well as additional unique challenges,” including the fact that there is no standardized system for reporting dog deaths.
The EOLS collects information on cause of death, reason for euthanasia, and perimortem quality of life in a standardized format. It will be used to build the DAP’s companion dog mortality information and perhaps other research projects.
“We anticipate that the EOLS data will provide new insights into companion dogs’ end-of-life experiences that will empower veterinarians to better care for their terminally ill and geriatric patients,” the authors wrote.