For most scientific experiments and biomedical research, mice and rats have been the preferred species due to their genetic similarities to humans and their anatomical and physiological likeness. Rodents are easy to maintain, have a short life cycle, abundant in genetic resources, and small in size, which can sometimes be a challenge when testing involves size variables that are closer to humans.
DNA methylation profiles serve as biomarkers or epigenetic clocks to monitor human and mammalian aging. Several new anti-aging interventions are being developed worldwide, and the follow on testing will occur in species that are evolutionarily closer to humans. These similarities pertain to the resemblance in size, high genetic diversity, and, given the environmental influence on DNA methylation, share the same environment as humans.
Domestic dogs are deemed in tone with these criteria. Humans and dogs share about 84 percent DNA, which proves beneficial for studies on human disease processes and, in line with this research, to evaluate the effectiveness of emerging anti-aging interventions.
Just like humans, canines also experience the same hallmarks of aging and development, including infancy, puberty, adulthood, old age, among others.
Furthermore, 340 recognized dog breeds worldwide represent an ideal system for studies of comparative aging, where within breed studies can be conducted in a background of limited diversity. While between breed studies recapitulate the levels of diversity observed in humans.
Read the original publication of this study here: [Epigenetic clock and methylation studies in dogs]
This study aimed to develop robust epigenetic clocks based on dog breeds that apply to both humans and dogs
Epigenetic clock and methylation studies in dogs
In this study led by Steve Horvath, a pioneer of epigenetic aging, a total of 565 blood samples were taken from 51 canine breeds. These samples were analyzed for methylation profiles and DNA methylation-based age estimators to be used in epigenetic clocks.
Mortality risk estimators were developed to model average time to death by further investigating the correlation between breed size and lifespan. CPGs with methylation changes that correlate with factors such as age, breed lifespan, and average weight were noted. The team noted that they’d look for changes that impacted lifespan and weight both dependently and independently of aging markers.
To generate dual-species (human-dog) clocks, researchers compared 1,207 human DNA methylation profiles from blood of various types of human tissues. This helped them isolate characteristics shared between canines and humans, and between humans and other mammalian species.
They created two different epigenetic clocks that applied to both dogs and humans.
One estimated chronological age, which is the length of time a being has been alive.
The second clock is relative age, which is the ratio of an individual’s current chronological age to the maximum recorded lifespan of the species.
Using this data, the team developed an epigenetic estimator of average time-to-death that can serve as a potential estimator of mortality risk for canines based on their blood methylation profiles.
Unfortunately, there is no absolute guarantee that an intervention that reverses epigenetic age in an animal model will successfully translate to humans, or vice-versa. However, the likelihood of success is increased by studies like this, which identify animals more suitable for being a model of human aging, and which develop human-animal dual-species clocks to translate the process of aging between species of different lifespans and physiology.
These results still need validation in clinical environments, but the methylation data so far looks hopeful.
Takeaways:
- Humans and dogs share about 84 percent of their DNA, which proves beneficial for studies on human disease processes and evaluates the effectiveness of emerging anti-aging interventions.
- Researchers developed a potential estimator of mortality risk for individual dogs based on blood methylation profiles.
- The presence of universal mammalian and dual-species clocks such as the human-dog clock provides evidence that mammalian intervention models which reverse epigenetic age may be transferable to humans and vice versa.
