The dog breeds that live longer than others – and why

A study tracking how DNA changes with age in dogs may have finally revealed why larger breeds have shorter life expectancy.

Among mammals, bigger is better when it comes to living a long life, with species like elephants living longer than tiny creatures such as mice. However, when you apply that pattern to a specific species, the reverse can be true.

Nothing demonstrates this theory better than dogs. It’s common to see small breeds such as Chihuahuas live into their teens, while larger breeds such as Great Danes typically live shorter lives, and the reason could be in their DNA.

Noah Snyder-Mackler, a professor at Arizona State University’s School of Life Sciences and Center for Evolution and Medicine was one of the authors of the study which was published in Science. He said: “We all know that big dogs usually don’t live as long as small dogs, but we have not known whether their cells actually age faster, or whether they simply hit certain diseases earlier.”

The process involved measuring blood samples from 894 dogs of various breeds, measuring DNA methylation, chemical tags which have some control over which genes are switched on and off. Using 1,640 blood methylation profiles, they were able to create an ‘epigenetic clock’ which could pinpoint a dog’s age with a margin of error of less than one year.

The study showed that larger dogs showed signs of accelerated aging, and dogs whose biological age appeared older than expected were at an increased risk of an early death. It was also shown that sex played a part in life expectancy. Males only have one X chromosome, and there researches found that LINE1 elements showed higher methylation in males.

“We found that large dogs show a faster-moving DNA methylation aging signature in blood, and that this acceleration is especially strong in parts of the genome that normally help keep ‘jumping genes’ quiet,” Snyder-Mackler said. Jumping genes, also called transposable elements, can copy themselves and insert into new spots in the genome. LINE1s ‌are a type of jumping gene that is normally kept silent by DNA methylation, but their ‌activation has been linked to genome instability, cancer and other age-related disease.

In large dogs, Snyder-Mackler said, “methylation at those regions appears to erode more quickly with age, as if the genome is losing some of the tape or clamps that keep these mobile elements suppressed.” This suggests that the shorter lives of large dogs reflect a faster molecular aging trajectory.

“If large dogs simply died earlier after following `the same molecular trajectory, we would look for late-life triggers of disease or mortality. But if parts of the aging program move faster throughout adulthood, as our data suggest for the blood methylome, then there may be processes we can measure, follow over time, and potentially modify before disease appears,” Snyder-Mackler said.

When it came to sex differences, Snyder-Mackler said: “In our genome-wide analyses, the sex signal looked distinct from the body-size signal, so I would treat that as a separate biology that needs follow-up rather than the same mechanism in disguise.” The ‌trade-off between large size and longevity may be a consequence of selective breeding rather than natural evolution. Humans bred dogs to grow ​quickly and reach large adult sizes for tasks such as guarding, hunting and herding.

“If selection strongly favors rapid growth or large adult size before old age, late-life costs can come along for the ride,” `Snyder-Mackler added. Previous explanations for why large dogs tend to have shorter lives focused on growth biology. Researchers have also suggested that larger dogs ⁠may undergo more cell growth, develop more quickly or face a higher risk of cancer.

“Our study does not replace those ideas; it gives us a molecular layer downstream of body size,” Snyder-Mackler said. The findings raise the possibility that slowing ​molecular aging could help extend healthy lifespan in larger dogs. Snyder-Mackler said, however, that ‌lifespan is not governed by a single biological clock. Large dogs ​would still face breed-specific risks, meaning that slowing molecular aging would not turn a Great Dane into a Chihuahua, in terms of lifespan, but could make one component of its aging trajectory slower.