Study of 894 dogs links faster aging in large breeds to loss of LINE1 methylation
A Science study of 1640 methylomes from 894 dogs found accelerated epigenetic aging in larger and male dogs, with size effects concentrated at transposable elements.
A team led by Noah Snyder-Mackler of Arizona State University analyzed 1640 methylomes from 894 dogs enrolled in the Dog Aging Project, according to a study published in Science. science.org
Sciencescience.orgOpen source ↗ The authors used DNA methylation to build an epigenetic clock and to test how the intrinsic rate of biological aging relates to lifespan, which varies widely among dog breeds.
Epigenetic clock and mortality
The clock predicted mortality. Dogs whose epigenetic age was older than expected had an elevated mortality risk, the authors report. Epigenetic aging was fastest early in life.
At orthologs of human age-associated genes, dogs showed concordant age effects on promoter methylation, which the authors interpret as conserved remodeling of immune pathways. Larger and male dogs, which are shorter lived, showed accelerated molecular aging. The two effects had different epigenetic architectures: sex-dependent methylation changes were concentrated on the X chromosome.
Transposable elements and body size
Size-associated methylation was especially pronounced at transposable elements (TEs). science.org
Sciencescience.orgOpen source ↗ Methylation declined broadly as dogs aged, most clearly in these mobile DNA sequences. More than 40 percent of LINE1-associated genome regions lost methylation with age, and the rate differed between dogs.
The loss was faster in larger breeds: they lost about 35 percent more LINE1 methylation per year than smaller breeds. LINE1 elements can damage DNA as they move through the genome, and methylation normally limits this activity.
Co-lead author Blaise Mariner said the result suggests that faster aging in larger dogs may be driven, at least in part, by reduced control over these elements. The authors identify TEs as potential mediators of size-associated lifespan and note that the sex-specific effects on the X chromosome may warrant further study.
Snyder-Mackler also said the findings suggest TEs may be a fundamental part of aging across mammals. This remains the authors' hypothesis: the study is a comparison of methylation patterns in dogs, and its conclusions about other species and about human therapies have not been tested here.
