We may finally know why big dogs die younger than smaller ones

Great Danes and mastiffs rarely live more than a decade, while Chihuahuas can live twice as long. Exactly why big dogs die younger than small ones do has been unclear — but new findings may help to solve that mystery.

The research, published Thursday (Oct. 8) in the journal Science, looked at a chemical code written on top of dogs’ DNA. This code, called the methylome, consists of chemical tags called methyl groups, which bind to DNA’s building blocks.

Proteins constantly access DNA, loading up the information written in its code and taking that data away to be turned into new proteins for the cell. But these methyl groups can act as tiny roadblocks that stop that process in its tracks.

These groups are one type of “epigenetic marker,” which collectively help to control gene activity, and their arrangement on DNA changes predictably as animals age, study co-author Blaise Mariner, a bioinformatician at Arizona State University, told Live Science. Across many studies and species, including humans, scientists have used this data to build epigenetic clocks that track animals’ biological ages.

Dogs happen to be a great species for studying aging. Their owners devotedly track what they eat, how they live, and how their health changes over time. So Mariner and his colleagues built epigenetic clocks using DNA in blood samples taken from 894 dogs enrolled in the long-term Dog Aging Project based at the University of Washington.

These samples revealed how the dogs’ immune cells aged. These cells patrol the whole body, so “they’re a really good measure of systemic aging,” study co-author Noah Snyder-Mackler, a genomicist at Arizona State University, told Live Science.

The team found that changes in DNA methylation closely tracked biological aging, in that the dogs with older-than-expected epigenetic ages had a higher risk of death from any cause. Once they looked at how different sizes of dogs aged, clear differences emerged.

“Using our biomarker, this epigenetic clock, big dogs were aging a little bit faster per year of life than small dogs,” Snyder-Mackler said.

A key epigenetic change linked to larger body size was the loss of methyl groups at stretches of DNA called transposable elements. Also called “jumping genes,” these elements can potentially move around the genome, but the methyl groups help stop them from doing so. But when that methylation is lost, the jumping genes can become too active and end up damaging other genes and causing inflammation, a key process that ramps up with age.

In short, the new data suggests that out-of-control jumping genes may contribute to big dogs’ faster aging.

In aging dogs, the team found that some regions of the genome with few chemical tags became more methylated, while other areas that had been choked with methyl groups gradually lost them. Additionally, at least in terms of their epigenetics, dogs’ immune cells appear to become more similar to one another as they age. Mariner said this “loss of cell identity” is a key hypothesis for what happens to the body as it ages.

Immune cells are carefully specialized for different roles, such as preventing cancer or killing viruses. As these cells become more similar to one another, they become less able to fulfill their specialized roles, studies suggest.

Humans have bred big dogs for size, and Snyder-Mackler said this push for large body size may have come at a cost.

“Their bodies have to make this trade-off between really rapid growth and maintenance of that,” he said, “versus investment in the immune system and integrity of the organism.” For now, that idea is a hypothesis, though, as the current study doesn’t directly address why big dogs’ epigenetic aging has come to be this way.

Now, the team wants to build more informative clocks as the Dog Aging Project recruits more pooches to follow for longer periods. Snyder-Mackler said the team’s data currently explains only part of how dogs’ epigenetic ages vary. “What we really want to know is, what explains the rest of that variation?” he said.

The team was keen to build predictive models that might help dog owners anticipate their pets’ age-related health concerns, Snyder-Mackler added.

What we learn about dogs from these studies may help us understand human aging, too. That’s partly because dogs get some of the same diseases we do, but it’s chiefly because they share humans’ living spaces and environments.

“We’re going to start looking, at the molecular level, [at] how these environmental exposures or experiences impact health and aging in dogs, which is going to be directly translatable to humans who are living in those same exact environments,” Snyder-Mackler said.

“Most people love dogs,” he added. “That means we can get a lot of really good data on them.”