Loyal The Consequences of Selective Breeding

Canine Aging Biology: Measuring Aging- Epigenetic Clocks

04.19.2021

Aging involves physical changes over time, but time is not the primary driver of these changes. Large-breed dogs age faster than small breed dogs, and there is great individual variation in the manifestations of aging. A key lesson we have learned is that chronological age and biological age are not identical. While we can measure chronological age easily, knowing the biological age of an individual is more useful in predicting and mitigating the health effects of aging.

The most effective tool discovered so far for measuring biological age is the epigenetic clock. As we age, our DNA undergoes a chemical change called methylation. Unlike DNA mutations, methylation does not affect the base pair sequence, so it is not a change in the genes themselves. However, the pattern of methylation influences the expression of individual genes, and this mechanism works on top of the DNA sequence (hence, “epigenetic”) to influence the phenotype of the organism.

The extent of DNA methylation can serve as a measure of both chronological and biological age. Epigenetic clocks are measurements of DNA methylation at multiple sites which correlate with chronological age. This may not seem very useful since we often know chronological age directly. However, epigenetic clocks also accurately predict future mortality even when other risk factors for death and disease are accounted for. In this way, they can measure biological age as well. Such epigenetic clocks may help us measure aging and predict health outcomes as well as assess the impact of anti-aging treatments.

Epigenetic clocks have been developed for dogs, and they have given us further insight into patterns of aging within the species. One study** developed a clock for dogs and grey wolves that correlates strongly with chronological age. This clock also demonstrates that age acceleration (the difference between chronological and biological age) is greater for larger breed dogs, again showing that these dogs age faster (Figure 1).

As part of the Healthspan study, we are hoping to further investigate the relationship between epigenetics and aging in dogs, so your work in this study is contributing directly to this exciting and powerful set of tools!

Figure 1. Age acceleration and dog breed. Age acceleration (difference between predicted epigenetic age and actual chronological age) is plotted against the maximum weight for the breed of each dog sample



**Thompson, M. J., von Holdt, B., Horvath, S., & Pellegrini, M. (2017). An epigenetic aging clock for dogs and wolves. Aging, 9(3), 1055–1068. https://doi.org/10.18632/aging...