UC San Diego researchers have developed a formula to more accurately compare dog age to human age by mapping molecular changes in the genome over time — a tool that might also help them assess how well anti-aging products work.
If there’s one myth that has persisted without much evidence over the years, it’s this: multiply your dog’s age by seven to calculate how old they are in “human years.” In other words, the old adage says a four-year – old dog is similar to a 28-year-old person in physiological age.
But a recent report by University of California San Diego School of Medicine researchers throws it out of the window. Then, they developed a model that compared the ages of humans and dogs with better accuracy. The theory is focused on evolving variations in dog and human genomes with methyl groups — how many of these chemical tags and where they are found — as they mature. Although the two animals are not aging at the same pace over their lifetime, it points out that this is not a strictly sequential analogy, as the rule of thumb of 1:7 years would imply.
The latest method focused on methylation, reported in Cell Systems today (July 2, 2020), is the first that is transferable through organisms. The researchers claim that, rather than just a parlor trick, it may be a valuable resource for veterinarians and for testing anti-aging treatments.
“There are a lot of anti-aging products out there these days — with wildly varying degrees of scientific support,” said senior author Trey Ideker, PhD, professor at UC San Diego School of Medicine and Moores Cancer Center. “But how do you know if a product will truly extend your life without waiting 40 years or so? What if you could instead measure your age-associated methylation patterns before, during and after the intervention to see if it’s doing anything?” Ideker led the study with first author Tina Wang, PhD, who was a graduate student in Ideker’s lab at the time.
The formula introduces a modern “epigenetic clock,” a tool for deciding a cell, tissue or organism’s age based on a reading of its epigenetics — chemical changes such as methylation that affect the genes are “off” or “on” without modifying the genetic sequence itself inherited.
Epigenetic shifts offer scientists clues to the age of a genome, Ideker said — much as wrinkles on a person’s face provide clues to their generation.
Ideker and others have previously published human epigenetic clocks but they are limited in that they can only be accurate for the specific individuals on whom the formulas were developed.
They don’t translate to other species, possibly not even to others.
Ideker said it was Wang who got him the dog concept in the first place.
“We always look at humans, but humans are kind of boring,” he said. “So she convinced me we should study dog aging in a comparative way.”
For this reason, Ideker and Wang collaborated with dog genetics experts Danika Bannasch, DVM, PhD, professor of public health and reproduction at the UC Davis School of Veterinary Medicine, and Elaine Ostrander, PhD, head of the Cancer Genetics and Comparative Genomics Division at the National Institute of Human Genome Science, part of the National Institutes of Health. Bannasch provided some 105 Labrador retrievers with blood samples. Ostrander was the first to sequence the dog genome and provided useful data on its study.
Dogs are a fun species to research, Ideker said. Given how close they live with us, maybe more than any other animal, the environmental and chemical exposures of a dog are very similar to humans, receiving almost the same levels of health care. It is also important that we better understand their ageing process, he said, as veterinarians often use the old 1:7-year ratio to determine the age of a dog and use that information to guide diagnostic and treatment decisions.
What resulted from the analysis is a graph that can be used to align the dog’s age with equivalent age in humans (see map above). The comparison over time is not one ratio of 1:7. Particularly when the dogs are young, they age rapidly in comparison with humans. A one-year-old dog resembles a human who is 30 years old. A four-year – old dog is like a human age 52. Then, by the age of seven, dog aging slows down.
“This makes sense when you think about it — after all, a nine-month-old dog can have puppies, so we already knew that the 1:7 ratio wasn’t an accurate measure of age,” Ideker said.
One drawback of the current epigenetic clock, according to Ideker, is that it was designed using a single dog breed, so it is understood that certain dog breeds live longer than others. More research will be needed, but since it’s accurate for both humans and mice and Labrador retrievers, he predicts the clock will apply to all breeds of dogs.
Next, the researchers plan on testing other dog breeds, determining whether the results hold up using saliva samples, and testing mouse models to see what happens to their epigenetic markers when you try to prolong their lives with a variety of interventions.
Meanwhile Ideker, like many other dog owners, is now looking a little differently at his own canine companion.
“I have a six-year-old dog — she still runs with me, but I’m now realizing that she’s not as ‘young’ as I thought she was,” Ideker said.
