Sled dogs are leading the way in their quest to slow aging
Dashing through the snow at 25 miles an hour, Heather Huson ’97 got her first thrill as a musher at age 7. From then on, she was hooked on dog sledding and raced competitively for nearly 30 years across North America.
By the end of her racing days, she had competed twice in sled dog races equivalent to the Olympics – the International Federation of Sled Dog Sports World Championships. And she ended her racing career in style, winning a fiercely competitive six-dog class race at the 2004 Tok Race of Champions in Tok, Alaska.
Now an assistant professor of animal science, Huson co-leads a $4.2 million project studying nearly 100 Alaskan sled dogs ages 8 to 13, former athletes past their glory days. The study, which began in 2018, is a quest for one of medicine’s holy grails: how to slow aging.
“This project allows me to work with sled dogs again, but now I study their aging and health,” said Huson, a molecular geneticist at the College of Agriculture and Life Sciences.
Huson and his co-director, Dr. John Loftus, assistant professor of small animal medicine at the College of Veterinary Medicine, are investigating whether a drug that inhibits an enzyme called reverse transcriptase can mitigate aging and prolong life in older dogs. . Private donations fund the project through the Vaika Foundation, a nonprofit group of scientists and veterinarians whose mission is to extend the health and lifespan of pets.
The project will serve as a proof of principle for whether reverse transcriptase inhibitors could be the elixir. If confirmed, new, finely tuned drugs could be developed for dogs and humans.
“While we love dogs and care about extending the lifespan of dogs, it’s also a really good role model for people, hopefully, in the future,” Loftus said.
Genetics of aging
Other researchers, including project collaborators at the Roswell Park Comprehensive Cancer Center in Buffalo, New York, have found evidence in mice that reverse transcriptase inhibitors suppress tumors and extend lifespan.
“The next step was to move to a model organism that is more closely related to humans in similar environments, and more similar to the types of diseases that people get,” Huson said.
In mammals, viruses that infected distant ancestors left behind part of their DNA, called genetic elements.
“As we age, we find that these normally dormant DNA elements activate” and then behave like viruses in the body, said Loftus, a veterinarian and researcher who leads immune system analysis on this project. “When DNA elements are activated, they can encode [for] a number of proteins, and reverse transcriptase is one of them.
In turn, reverse transcriptase plays a role in duplicating more of these genetic elements, which insert themselves randomly into the genome and can lead to mutations and cancer.
And since these elements act like viruses in the cells, they also trigger an immune response, which creates inflammation.
The federally approved drug being tested in the sled dog project is commonly prescribed to people with viral infections.
“Our approach will be to give dogs a reverse transcriptase inhibitor to turn off the transcriptase,” Loftus said, “and hopefully reduce inflammation, reduce the incidence of cancer and other mutation-related diseases. and DNA damage, and ideally increase life span.”
Why Alaskan Sled Dogs?
Dogs offer many advantages over mice as research subjects. They share similar lifestyles and age-related diseases like cancer and cognitive dysfunction with humans, and serve as a model for studying Alzheimer’s disease.
Originally, researchers proposed to study companion dogs. But maintaining a consistent diet for all participants and trusting owners to administer the drug consistently proved too unreliable.
“Rather, we came up with the idea of creating a colony of dogs that we had control over,” Huson said. They realized that sporting dogs were housed in groups, in kennels, and as they got older, owners kept their best dogs and often sold the rest to hobbyists or as pets.
“So that gave us an avenue of how we could get these dogs,” Huson said.
For her doctorate, Huson studied the genetics and selective breeding of Alaskan sled dogs at the University of Alaska, Fairbanks. She discovered that sled dogs are a genetically distinct breed. They have undergone intense selection for traits such as athleticism, but at the same time are subject to an open breeding scheme, with a diverse gene pool that results in fewer genetic issues and diseases than purebreds.
“Yet they’re creating a unique population that’s still homogeneous that we can study and say, this drug response is potentially drug-related and not because it’s a poodle versus a beagle,” Huson said.
In late May 2018, Huson and Loftus began acquiring dogs, which they bred at the Baker Institute for Animal Research at Cornell. Huson has been to Alaska twice, and she and others, including students, have picked up dogs from Canada, Michigan, Minnesota, Oregon, Washington and other states.
Locating the dogs and bringing them to the Baker Institute required countless trips across the country by plane and vehicle. As of September 2018, they had 102 dogs for the study. In March 2019, researchers collected the first baseline data.
Test aging over time
To test the drug’s effectiveness, Huson and Loftus quantified aging in dogs every six months across three avenues — immune function, behavior, and body condition. All tests are non-invasive or minimally invasive.
They are testing two types of immune responses: adaptive responses that react quickly to infections; and innate responses where the immune system recognizes and delivers specific antibodies to fight off a pathogen that has previously entered the body. They also check the blood for increased markers of inflammation.
Four behavioral tests for cognitive dysfunction involve an empty behavioral testing room with a video camera to record dogs alone when they encounter such things as a stranger sitting motionless in a chair, a familiar or new toy, or a mirror.
For physical testing, dogs are fitted with a running harness and are trained to run on a treadmill with heart rate and EKG monitors. The treadmill has special sensors under the belt to register the pressure of each step, to detect lameness that might come with arthritis. Another test times the dogs as they pull one and a half times their body weight over a distance of 40 meters using a pulling harness.
It will take years to gather enough data for researchers to make a definitive statement about the drug’s effects. But funds have already been allocated to provide dogs with a high quality of life until they die of natural causes.
Twice a day the dogs come out to play. As soon as the kennel doors open, the dogs, tongues flailing, rush excitedly down a long hallway toward the light of an open door that leads to three separate fenced areas where they play, run, sniff the grass and greet student volunteers outside.
It reminds Huson of his childhood, when his family owned up to 50 sled dogs.
“I used to train dogs to run all the time,” Huson said. “Now we are training them to run in a slightly different scenario. It’s fun and rewarding. And it’s therapy for us.