Epigenetics

Epigenetics is the study of how behavior and environment can affect the way genes work. Unlike traditional genetics which focuses on the sequence of DNA bases (i.e., the “genetic code”), epigenetics is a newer research area dedicated to understanding the processes involved in turning genes on and off. These processes can be dynamic and reversible, and learning more about them offers insights into what affects gene expression and how gene expression may change over time.

Did you know? The Greek prefix “epi” translates to “outside of” or “over,” so the word “epigenetic” literally means “above genetics” referring to a level of information above the DNA base sequence.
Why is studying epigenetics important?

Epigenetic processes are natural and essential to many cellular functions, but some epigenetic changes can have adverse health impacts. For instance, studies have shown that epigenetics changes may affect behavior, vulnerability to disease, and perhaps most importantly of all, longevity. By studying epigenetics, we can gain important insights into how to potentially improve both healthspan and lifespan.

What are epigenetic changes?

Epigenetic changes are additional information layered on top of the sequence of letters (A,T,G and C) that makes up DNA. One of the best-understood is DNA methylation, which is what we are focusing on in the XTD study. It involves a methyl group — which is one carbon atom combined with three hydrogen atoms (CH3) — being added to a DNA strand at a specific location. Generally, adding the methyl group turns the gene nearest to it “off,” leading to its deactivation. Conversely, removing the methyl group turns the gene “on,” leading to its activation.

What can epigenetics tell me about my dog’s health?

In humans, changes in DNA methylation correlate with many factors, including lifespan and healthspan1, disease2, environment3, and exposure to cigarette smoke4 –to name just a few. Some of these correlations, such as age, have been explored in canines, as well5,6. Measuring DNA methylation across thousands of different dogs can help us better understand the factors impacting the healthspan and lifespan of dogs.

How are epigenetic tests conducted?

We measure a dog’s DNA methylation pattern by analyzing their saliva sample with a technique called bisulfite sequencing. This involves treating the DNA with a chemical called bisulfite, which transforms the DNA so that the methylation pattern can be easily read using standard DNA sequencing methods. This method also provides some useful data on a dog’s genotype, like which alleles, or forms of a gene, they have.

Additional reading:

“Epigenetics 101: a beginner’s guide to explaining everything”

“What is epigenetics?”

Citations

1Lu AT, Quach A, Wilson JG, Reiner AP, Aviv A, Raj K, Hou L, Baccarelli AA, Li Y, Stewart JD, Whitsel EA, Assimes TL, Ferrucci L, Horvath S. DNA methylation GrimAge strongly predicts lifespan and healthspan. Aging (Albany NY). 2019 Jan 21;11(2):303-327. doi: 10.18632/aging.101684. PMID: 30669119; PMCID: PMC6366976.

2Falahi, F., van Kruchten, M., Martinet, N. et al. Current and upcoming approaches to exploit the reversibility of epigenetic mutations in breast cancer. Breast Cancer Res 16, 412 (2014).https://doi.org/10.1186/s13058-014-0412-z

3Law PP, Holland ML. DNA methylation at the crossroads of gene and environment interactions. Essays Biochem. 2019;63(6):717-726. doi:10.1042/EBC20190031

4McCartney DL, Stevenson AJ, Hillary RF, Walker RM, Bermingham ML, Morris SW, Clarke TK, Campbell A, Murray AD, Whalley HC, Porteous DJ, Visscher PM, McIntosh AM, Evans KL, Deary IJ, Marioni RE. Epigenetic signatures of starting and stopping smoking. EBioMedicine. 2018 Nov;37:214-220. doi: 10.1016/j.ebiom.2018.10.051. Epub 2018 Oct 30. PMID: 30389506; PMCID: PMC6286188.

5Thompson MJ, vonHoldt B, Horvath S, Pellegrini M. An epigenetic aging clock for dogs and wolves. Aging (Albany NY). 2017; 9:1055-1068. https://doi.org/10.18632/aging.101211

6Wang, T., Ma, J., Hogan, A., et al. Quantitative Translation of Dog-to-Human Aging by Conserved Remodeling of the DNA Methylome. Cell Systems. 2020; 11 (2): 176-185. doi: https://doi.org/10.1016/j.cels.2020.06.006