Few animals show the link between body size and lifespan as clearly as dogs. Within a single species, large breeds such as Great Danes typically die younger than small breeds such as Chihuahuas.
A new study suggests that differences in how DNA changes with age may help explain why.
The pattern is striking because it runs counter to what we see across mammals: larger species, such as elephants, generally live longer than smaller ones, such as mice. Within a species, however, the relationship can reverse.
Previous studies have linked certain biological mechanisms to exceptional longevity across species, but these comparisons offer less insight into why some individuals live longer than others within the same species.
“We know big dogs tend to live shorter lives than small dogs, but it’s unclear whether their cells age faster or they develop diseases earlier,” said Noah Snyder-Mackler, a professor at Arizona State University’s School of Life Sciences and Centre for Evolution and Medicine and co-author of the study published in the journal Science.
To investigate, researchers measured DNA methylation—chemical tags that regulate gene activity—and used age-related patterns to build an epigenetic clock that estimated dogs’ ages with a median error of less than a year.
Analysing 1,640 blood methylation profiles from 894 pet canines of various breeds, they found that larger dogs and male dogs showed signs of accelerated molecular ageing, while dogs whose biological age appeared older than expected based on the profiles faced a higher risk of early death.
“We found that large dogs show a faster-moving DNA methylation ageing 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 diseases.
In large dogs, Sny der-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 ageing 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 ageing 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.
