Study links larger dog size to faster molecular ageing

Mixed · 2A new study published in the journal Science indicates that large dogs age faster at a molecular level than small dogs, which may help explain why large breeds such as Great Danes typically die younger than small ones such as Chihuahuas. 1 2 Mixed · 2The researchers measured DNA methylation, chemical tags that help control which genes are switched on and off, and used age-related patterns in them to build an epigenetic clock that estimated a dog's age with a median error of less than one year. 1 2 Mixed · 2Analysing 1,640 blood methylation profiles from 894 pet dogs of various breeds, they found that larger dogs and male dogs showed signs of accelerated molecular ageing, and that dogs whose biological age appeared older than expected faced a higher risk of early death. 1 2

Mixed · 2Noah Snyder-Mackler, a professor at Arizona State University's School of Life Sciences and Center for Evolution and Medicine and one of the study's authors, said the acceleration in large dogs is especially strong in parts of the genome that normally keep 'jumping genes' (transposable elements) quiet. 1 2 Mixed · 2Jumping genes can copy themselves and insert into new spots in the genome; one type, LINE1, is normally silenced by DNA methylation, and its activation has been linked to genome instability, cancer and other age-related disease. Snyder-Mackler said methylation at those regions appears to erode more quickly with age in large dogs. 1 2 Mixed · 2The study also found differences between males and females, largely on the X chromosome, where LINE1 elements showed higher methylation in males. Snyder-Mackler said the sex signal looked distinct from the body-size signal and should be treated as separate biology needing follow-up. 1 2

Mixed · 2The authors suggest the trade-off between large size and longevity may stem from selective breeding rather than natural evolution, since humans bred dogs to grow quickly and reach large sizes for guarding, hunting and herding. Snyder-Mackler said late-life costs can 'come along for the ride' when selection favours rapid growth or large adult size. 1 2 Mixed · 2Earlier explanations focused on growth biology, such as more cell growth, faster development or higher cancer risk. Snyder-Mackler said the study does not replace those ideas but gives a molecular layer downstream of body size. 1 2 Mixed · 2The findings raise the possibility that slowing molecular ageing could extend healthy lifespan in larger dogs, though Snyder-Mackler cautioned that lifespan is not governed by a single clock and that slowing it would not turn a Great Dane into a Chihuahua in lifespan terms. 1 2