The size of dogs significantly influences not only their physical characteristics and abilities but also the rate at which they age. Among dog enthusiasts, it is widely acknowledged that a Chihuahua can outlive a Labrador, often enjoying better health in the process. However, the biological mechanisms behind this disparity remain somewhat elusive.
Investigating Genetic Factors in Ageing
Recent research spearheaded by scientists at Arizona State University suggests that the answer may lie in how bodies regulate “jumping genes,” or transposable elements, which are fragments of DNA capable of duplicating themselves and inserting copies into various locations within the genome. This process can alter the structure or functionality of specific genetic regions.
The researchers arrived at this conclusion after examining 1,640 molecular profiles of DNA from 894 domestic dogs. The study focused on DNA methylation, a process wherein the organism incorporates chemical markers into particular areas of genetic material. These markers help regulate gene activity by influencing which genes are activated or silenced.
As methylation patterns tend to change over time, they serve as a useful tool for exploring biological ageing and its potential discrepancies compared to chronological age. Using this natural behaviour, the team developed an epigenetic clock, a model that estimates an organism’s biological age through the chemical marks present in its DNA. By comparing the estimates from this model with the animals’ chronological ages, the researchers identified variations in the ageing processes of dogs and examined how these differences relate to size and sex.
Ageing Rates in Large Breeds and Females
The findings revealed that the pace of ageing correlates with a gradual loss of methylation in various genomic regions. According to the study published in the journal Science, this decline in regulatory markers was particularly pronounced in areas containing a specific type of jumping gene known as LINE-1 elements.
Importantly, the research highlights that over 40% of the genomic regions associated with LINE-1 experience a loss of methylation as dogs age. However, this phenomenon does not occur uniformly across all breeds. In larger dog breeds, the deterioration of methylation in these elements is observed to be up to 35% more pronounced each year compared to smaller dogs.
Blaise Mariner, a researcher from the College of Biological Sciences and the Centre for Evolution and Medicine at Arizona State University, and co-author of the study, stated, “This is one of the clearest molecular signatures we have observed that aligns with the well-known relationship between size and lifespan in dogs. It suggests that the accelerated ageing in larger dogs may be partially due to reduced control over these ‘jumping genes.’”
Sexual Dimorphism in Methylation Patterns
The study also uncovered differences in the methylation of LINE-1 elements located on the X chromosome between male and female dogs. Males possess an XY chromosomal composition, while females have two X chromosomes (XX). In males, these elements exhibited higher levels of methylation.
Nevertheless, the researchers caution that further investigation is necessary to confirm whether these differences contribute to the distinct ageing patterns observed between males and females of the same breed.
Understanding Ageing in Dogs and Beyond
The authors of the study emphasise that their findings do not definitively establish whether the activity of LINE-1 elements is a cause or a consequence of ageing. Nonetheless, they argue that the research provides compelling evidence that epigenetic changes in these genomic regions are characteristic of biological ageing and may help elucidate why this process varies among individuals.
This discovery could have significant implications for understanding ageing in other mammalian species, including humans, and pave the way for developing treatments aimed at prolonging healthy lifespans.
Noah Snyder-Mackler, a professor at the College of Life Sciences and the Centre for Evolution and Medicine at Arizona State University, and co-author of the study, concluded, “As companion animals, dogs can also serve as a valuable model with immediate relevance for human health. Our work suggests that transposable elements may be a fundamental part of the ageing process in mammals. If this is the case, targeting these elements or the mechanisms that regulate them could provide a promising avenue for future therapies aimed at extending healthy life expectancy in humans.”