Dog

Nine-year-old Bagel sits patiently as Dr. Ryan Baumwart gives her an exam at WSU in Pullman to see if she meets the criteria to be part of the Dog Aging Project, Friday, March 18, 2022. In the background at left, helping out, is licensed veterinary technician Janel Holden. (Ellen M. Banner/The Seattle Times/TNS)

SEATTLE — If it weren't for squirrels, Bagel probably wouldn't be here today at Washington State University's College of Veterinary Medicine. The yellow Labrador was destined to be a guide dog for the blind but flunked out because she was distracted by small animals. Now, this otherwise very good girl has a second chance to be of service — by participating in the most comprehensive study ever conducted of health and aging in dogs.

Bagel's owner, Brenda Voght, volunteered her to join a research "pack" that already includes more than 37,000 pet dogs across the country and is expected to swell to 100,000. Called the Dog Aging Project, the ambitious undertaking seeks to answer many of the questions dog owners ask — and often anguish over: Why do some breeds live longer than others? How do genetics, environment and lifestyle affect longevity and the risk of disease? And, above all: How can we ensure our beloved companions stay healthy, happy and active for as long as possible?

"I would like to know if there is something we can do as humans, as their partners, to extend their lives a little longer," says Voght. After her last dog died, it was a year before she was able to open her heart to another puppy.

She fostered Bagel for about a year, then adopted her after the canine's "career change" — the gentle euphemism used when guide dogs don't make the cut.

On average, yellow Labs live 10 to 12 years.

Bagel is 9.

THE PROJECT WELCOMES dogs of all types and ages and plans to track them for at least 10 years, says Daniel Promislow, an evolutionary geneticist at UW Medicine who co-founded the initiative and helped assemble a national team of more than 80 researchers, veterinarians and data scientists to coordinate the massive undertaking.

No one has ever investigated such a large number of dogs over such a long period of time, especially at the level of detail Promislow and his colleagues envision. One branch of the study is sequencing the genomes of at least 10,000 dogs. Another zeros in on the oldest dogs in the pack — the "supercentenarians" — to look for keys to their longevity.

"All of us are really excited about what will come out of it," says Elaine Ostrander, who pioneered genetic analysis of dogs more than two decades ago in Seattle at the Fred Hutchinson Cancer Research Center. She now works at the National Human Genome Research Institute.

It's long been clear that big dogs have shorter lifespans than small dogs, and that different breeds are predisposed to different ailments, says Ostrander, who is not involved in the project. Golden retrievers are prone to cancers. German shepherds often develop hip dysplasia. Doberman pinschers have a high prevalence of heart disease. The Dog Aging Project will help reveal more about the mechanisms behind those links, she says.

"They're going to be able to make those connections pretty tightly because their data set is the biggest one out there."

The researchers also hope to gain insights into normal aging, along with the entire spectrum of ailments that plague older dogs, from arthritis and hearing loss to cataracts and cognitive decline. Discovering ways to help dogs live longer would be wonderful, says Promislow. But the primary goal is to prolong "health span" — that golden period of well-being when dogs can leap and dive and fetch and snuggle free from pain or disability.

"We want to help each dog live the longest, healthiest lifespan that it can," he says.

The findings could be relevant to human health as well.

Dogs suffer from many of the same diseases we do. And unlike mice and other animals used in laboratory studies, dogs are genetically diverse. They live in our homes, breathe the same air and experience the same conditions.

The sad fact that dogs' lives are shorter than ours means it's possible to gain that knowledge more quickly by focusing on humanity's best friends.

MOST OF THE ANIMALS enrolled in the Dog Aging Project never have to leave their home turf. Owners fill out an annual, 116-page questionnaire that covers everything from diet and mobility to temperament, favorite types of toys, bowel habits, pesticide exposure, health status and sleeping arrangements. Environmental data, like air and water quality, is correlated to each dog's geographic location. Participants also can upload their dogs' veterinary records, and more than 15,000 already have done so.

Dog owners are integral to the project, which keeps them in the loop with blog posts and a dedicated social media platform called the "Dog Park." It's the kind of science that cuts across politics, demographics and geography because so many Americans are crazy about dogs, Promislow says.

"I'm really excited about the ability ... to bring science to the lives of people in a way that's fun and informative and educational."

A small subset of canines are candidates for more intensive study, which is why Voght made the drive from her home in Bothell to the other side of the state. Bagel is being evaluated for the most high-profile arm of the project: a clinical trial of a potential anti-aging drug.

Called rapamycin, the medication is used in human transplant patients to prevent organ rejection. But studies in yeast, worms and mice show that low doses can extend lifespan by up to 25%. Rapamycin also delays age-related maladies such as cognitive decline and cancer, and boosts heart health in mice.

Dr. Kate Creevy, chief veterinary officer for the project, is optimistic it might do the same for dogs. In one small trial, dogs who got the drug showed improved heart function. In another, owners said their dogs seemed more active.

Now, the team is recruiting 500 senior dogs for a year of treatment and two years of follow-up. Half the dogs will get rapamycin, and half will get a placebo. Neither owners nor scientists will know which until the end.

"Even if we don't actually change lifespan, if we improve the experience of aging, that will be really, really valuable to dogs and the people who love them," says Creevy, of Texas A&M University.

The dogs in the study need to be healthy, so Bagel is getting the type of checkup available only in a veterinary teaching hospital such as WSU's. Staff leads her into an exam room, where she obligingly hops on the table and rolls onto her side.

Technicians shave a small patch of fur for analysis, draw blood, measure blood pressure and attach electrodes to monitor her heartbeat. Dr. Ryan Baumwart, a veterinary cardiologist, checks Bagel's eyes and probes her heart with ultrasound, displaying the image of the beating organ on a wall-mounted computer screen.

The study is just getting started, and, so far, only about half of dogs examined have qualified. Bagel's scans look promising, Baumwart says. Now, it's a matter of waiting on the blood tests.

THE DOG AGING PROJECT reflects a new approach to the most common causes of death in canines and people, says co-director and UW Medicine pathologist Matt Kaeberlein, who studies the basic biology of aging. Most research focuses on specific diseases, such as cancer or Alzheimer's. But nearly all of the major killers are strongly linked with age, so Kaeberlein argues that it makes sense to focus on the aging process itself.

"If we can understand aging biology and what it is at a cellular, molecular, mechanistic level, then maybe it will be feasible to target that biology with interventions," he says. Those might be nutritional strategies, drugs or gene therapy, with the goal of lowering the risk of all age-related diseases.

For example, rapamycin seems to work at least in part by reducing inflammation, which increases with age and impairs immune function. Older animals also accumulate more cellular debris, and rapamycin revs up the process of clearing it away.

Another arm of the project, called the Precision Cohort, will delve in unprecedented detail into biochemical changes and shifts in gene expression over time in 1,000 dogs.

"We will know more about the biology and physiology of those dogs than probably anybody has ever known about dogs before," Kaeberlein says. "We will be collecting very high-resolution data to try to understand ... the relationship between their unique genetic makeup and their unique environment that's influencing the aging process."

One of those dogs is Hana, a 3-year-old Cavalier King Charles spaniel with long, silky ears who lives on Bainbridge Island. Her owner, Masami Shimizu-Albergine, is a researcher herself and was eager to help.

Once a year, Hana's vet collects blood, urine, feces and hair samples for analysis at specialized labs. It's a level of medical monitoring few humans receive, and it will help pin down the role of gut microbes, metabolic function, toxin exposure and a host of other factors.

"There's really no end to what we can discover," Promislow says.

ANALYZING THE GENOMES of 10,000 dogs will uncover the genetic basis for a large swath of canine diseases, says Joshua Akey, a geneticist who started working on the dog project at the University of Washington and is now at Princeton University's Lewis-Sigler Institute for Integrative Genomics.

As in humans, though, it's not likely to be simple. Most diseases result from multiple genes and environmental factors. But Akey says it should be possible to develop risk scores to alert owners to their dogs' genetic predispositions. One UW researcher is focused on dogs with lymphoma, looking for a genetic biomarker for early diagnosis.

The link between a dog's size and lifespan appears to have a strong genetic basis. Big breeds have higher levels of a protein called IGF-1 (insulin-like growth factor), which is involved in regulating growth. In mouse studies, dialing down that protein can extend life and improve health.

So even though it might be possible to improve health for all dogs, a 150-pound Great Dane likely will never match the longevity of a 15-pound Chihuahua, Creevy says.

Distinct breeds were developed only in the past few centuries, and the trove of genetic information compiled for the project will help retrace that process. It could even settle the debate over when wolves were first domesticated and morphed from Canis lupus to Canis familiaris.

"Some people say it was 10,000 years ago, and others have argued it was much longer," Akey says. "I think we'll have a data set that can definitively answer some of these evolutionary questions."

PROMISLOW, CREEVY and Kaeberlein started kicking around the idea of a major dog study more than a decade ago. It took years to lay the groundwork and convince federal funders of its worth. Their first major grant — $25 million from the National Institutes of Aging — was awarded in 2018. The team also has funding from foundations, tech entrepreneurs and small donors such as the Irish wolfhound Association of New England.

All of the data will be freely shared online. The first batch, from about 25,000 dogs, was recently posted and already is showing some intriguing correlations. For example, dogs fed once a day appear to have higher cognitive scores and fewer health problems than dogs who eat multiple times a day.

That doesn't prove cause and effect, Kaeberlein cautions, but it's a place to start digging deeper.

The project also has the potential to provide some of the best comparisons of dog diets, which now come in a dizzying array, from dry kibble to small-batch artisan concoctions. Promislow, who never imagined he would be cooking for a dog, started preparing a mix of sweet potatoes, oats, ground chicken and kibble for Frisbee, his 16-year-old mixed-breed female, after she was stricken with severe diarrhea.

"We can do the careful science to evaluate the effects of raw-food diets, home-cooked diets, et cetera," he says. "We will soon have more data than any other study on the consequences of a grain-free diet."

THE PROJECT IS nonprofit, but entrepreneurs are keen to apply the information it generates. Americans spent almost $104 billion on pet care in 2020, and the trendline points up, according to the American Pet Products Association.

Startups already are chasing more sophisticated genetic testing and anti-aging drugs for dogs. But they can't generate the massive amounts of data or conduct large-scale clinical trials like the Dog Aging Project does, says Celine Halioua, founder and CEO of Loyal. Kaeberlein is a scientific adviser to the Bay Area biotech, which is testing two drugs to increase health span in dogs.

The dog-aging database will be an invaluable resource, Halioua says.

"It's a gift to the aging field for them to be doing this."

A WEEK AFTER the visit to WSU, Voght got the news: Bagel qualified for the rapamycin trial. She'll get a once-a-week dose, either real or placebo, for the next year, and physical exams every six months through 2025. Voght won't know until then whether Bagel's pills are real. Either way, she's willing to keep making the trip to Pullman in hopes that the project will benefit Bagel, other dogs — or even people.

She's not expecting miracles, though.

Bagel is already slowing down a bit, and her face is frosted with white. "If Labs can make it into the double digits, you're lucky," Voght says.

So she recently adopted what she calls her transition dog — a 2-year-old black Lab named Delray.

"It's nice to have another dog in the house to help you a little bit," she says. "For when that time comes."

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