Big dogs age faster – ‘jumping genes’ may be why
Arizona State University researchers found giant breeds lose approximately 35% more LINE1 methylation a year than small ones, on average, though more research is needed to tell whether that is a cause or a consequence of aging.
Big dogs age faster than small ones at a molecular level, and weaker control over so-called “jumping genes” may be part of the reason, researchers at Arizona State University have reported.
The study, published in Science on 8 October, mapped genome-wide patterns of DNA methylation in dogs enrolled in the Dog Aging Project. DNA methylation is part of the epigenome, which influences how much genes are turned on or off without changing the sequence of DNA in each gene, the university said.
Across mammals, bigger species typically live longer, from a couple of years for mice to almost 200 years for some whales. Within a species the opposite is often true, and dogs are one example.
Senior author Noah Snyder-Mackler, a professor at Arizona State University’s School of Life Sciences and Center for Evolution and Medicine, said dogs “show dramatic variation in lifespan within a single species”.
Aging was associated with a widespread loss of these methylation marks, particularly in regions of the genome known as “jumping genes” or transposable elements. One class, called LINE1s, was found to be a key component of differences in biological aging.
LINE1s can copy and insert themselves throughout the genome, damaging DNA in the process. They are usually kept in check by DNA methylation, but their activity can increase when the marks are lost, a process linked to genomic instability, cancer and other age-related diseases.
More than 40% of LINE1-associated regions lose methylation with aging, making them the most affected class of transposable elements. The loss is not even: larger breeds experience significantly faster declines, and giant breeds lost approximately 35% more LINE1 methylation per year than small breeds.
“This is one of the clearest molecular signatures we’ve seen that aligns with the well-known size-lifespan tradeoff in dogs,” said co-author Blaise Mariner, also a researcher at the university.
Sex made a difference too. The abstract says male dogs, like larger ones, are shorter lived and show accelerated molecular aging.
LINE1s on the X chromosome were more methylated in males than in females. “This was an unexpected result,” said Brianah McCoy, who co-led the work during PhD research at the university.
The team also developed an epigenetic clock that predicted mortality, the abstract says, and found that epigenetic aging is fastest early in life.
The university said more research is needed to determine whether LINE1 activity is a cause or a consequence of aging.
“Our work suggests that transposable elements may be a fundamental part of the aging process across mammals,” Snyder-Mackler said. “If that’s the case, targeting these elements or the mechanisms that regulate them could be a promising avenue for future therapies to extend the health span in humans.”
