Researchers hope to use canines to unlock the secrets of human aging and identify anti-aging therapies.(pxfuel)
The fountain of youth for man’s best friend may be within hand’s (or paw’s) reach. With the collective effort from research projects and biotech startups, we’re making such significant strides towards prolonging the longevity of dogs that we may soon see the approval of lifespan-extending drugs in canines. But the quest doesn’t stop with dogs; scientists hope that these findings will have major consequences for understanding how people age and how to do so more healthily.
To study aging in dogs, we first need to know how dogs age biologically and how this tracks with people. Many dog owners and puppy aficionados have probably tried to do mental gymnastics to figure out how old a canine is in human years. While we like to think that the relationship between dog years and human years is based on simple multiplication, a recent study published in Cell Systems sought to debunk one of the most common myths about dogs: much to our surprise, one “dog year” does not equal seven “human years.”
The research group at the University of California, San Diego (UCSD) found that the relationship between canine and human age is not linear but can be solved by a logarithmic formula. The formula for dog age in human years goes like this: 16 multiplied by the ln(age in dog years) plus 31 equals age in human years, where ln means “natural logarithm.” This formula was derived from the concept of the epigenetic clock, or the aging of the DNA in one’s genes, as a determinant of biological aging.
According to this logarithmic model, younger dogs age relatively “faster” than old ones. This means that a one-year-old puppy is equivalent to approximately 30 years in human years, but later in a dog’s life, the relative canine aging compared to human years slows. With that, a 4-year-old dog is more like a 52-year-old human (as opposed to a 28-year-old), a 9-year-old canine is closer to 66 years in human years, and a 10- or 12-year-old dog levels out at about 70 human years.
One of the major problems with creating anti-aging drugs and therapies is that people are already living overextended lives. It’s hard to quickly study the effects of any anti-aging therapeutic on people because a proper experiment will take tens of years, even hundreds. What’s more, the Food and Drug Administration (FDA) is more welcoming to drugs and treatments that tackle specific illnesses or symptoms.
This begs the question, is there a better way to study aging as it relates to humans? Although scientists often turn to mice or our closest evolutionary relatives, non-human primates, the answer to solving aging may be best suited for canines. That’s why it’s essential for scientists to have a handle on the biological age of dogs — so that we can understand the factors that drive canine healthspan and find therapeutics that can stall or reverse aging.
Along these lines, the Dog Aging Project follows tens of thousands of dogs for a decade to pin down the biological and environmental factors that maximize healthy canine longevity. Since some dogs, like some people, age well and others age poorly, the Dog Aging Project aims to understand how different factors — such as genes, lifestyle, and the environment — influence aging.
For example, dogs live shorter lives than humans, with smaller breeds living up to 18 years. Larger canines have a short time as a puppy, grow into adulthood more quickly and spend more time as a senior. Small dogs stay in that healthy middle-age window for a longer time. Researchers just aren’t sure why.
The Dog Aging Project started with 10,000 dogs in late 2019. Now, the project has almost 30,000 dogs, which researchers aim to follow for at least five years and hopefully their lifespan. Volunteers answer extensive surveys of 300 to 400 questions about their dog’s life, from where they sleep to how much they sleep, what kind of toys they play with, how much and what type of food they eat, and how many times a day. Researchers follow up at least once a year for the rest of the dog’s life.
“Sometimes dogs are fed one time a day, or sometimes it’s three times, or the food is left out all day. There’s everything in between, and we’re looking to see what shape they’re in and study what’s different among the dogs and how their life unfolds,” said Kate Creevy, the Dog Aging Project’s chief veterinary officer and associate professor in the Department of Small Animal Clinical Sciences at Texas A&M University. “It’s not that different from human aging and intermittent fasting, and looking at the dogs who are fed once a day — is there any benefit versus the dogs who are fed three meals a day.”
The Dog Aging Project also is exploring anti-aging therapeutics. A subset of participating dogs will be selected to be part of a new clinical study to examine the potential of the drug rapamycin to improve healthspan. Rapamycin, also called sirolimus, is a prescription medication used in humans to treat cancer and prevent organ rejection in transplant patients. Rapamycin seems to affect how their bodies age positively when used at very low doses in laboratory mice. We are interested in discovering whether these benefits could be seen in dogs and whether there are unwanted side effects.
Although the Dog Aging Project seems to have its sights currently set on rapamycin as it’s candidate of choice, there’s an array of compounds that have a physiological benefit or provide protection against chronic disease like pharmaceuticals and nutraceuticals that can be tested for anti-aging potential in canines. For example, we still don’t fully grasp if and how senolytics — drugs that target non replicating cells linked to certain chronic diseases and aging — work to improve healthspan and longevity.
Plus, some of the world’s leading anti-aging researchers like Dr. David Sinclair are very keen on a class of molecules called NAD+ precursors like nicotinamide mononucleotide. These compounds have shown promise in many rodent studies over the past decade and have recently supported some exciting results in a handful of human trials pertaining to metabolism and exercise. Yet, there is a lot of potential benefit from anti-aging studies in dogs for the aforementioned reasons of the difficulty in performing aging trials in humans and the vastly superior similarity of dogs to ourselves compared to rodents.
This anti-aging information isn’t intended to be used just for our canine companions; it’s also intended to be applied to humans. The hope is that this information will help dogs and people increase healthspan, the period of life spent free from disease.
And there’s a growing list of players in the field of dog aging. A startup called Cellular Longevity Inc. is working on an experiment through its brand Loyal that would make dogs live longer and live more active lifestyles. “Dogs are unquestionably considered the best model of human aging,” said founder Celine Halioua. “We have co-evolved with them, and they have a shared environment with us. They also develop age-related diseases over time. If we can do this for dogs, people will want it, too.”
Even George Church, the Harvard Medical School professor who is a genetics and synthetic biology leader and a prolific entrepreneur, is delving into dog anti-aging. The stealth startup Rejuvenate Bio, cofounded by Church, thinks dogs aren’t just man’s best friend but also the best way to bring age-defeating treatments to market. Back in 2018, Church said, “We have already done a bunch of trials in mice, and we are doing some in dogs, and then we’ll move on to humans.”
As it stands, it’s probably likely that dogs will start receiving the benefits of anti-aging therapeutics long before we will. Our journey with these domesticated descendants of wolves will continue to be intertwined, perhaps now more than ever.