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What is Epigenetics?
Here at EpiPaws, we are obsessed with epigenetics.
But what is it?!
If we break down the word epigenetics, "Epi" in greek means "above" or "on top of" indicating that epigenetics refers to something happening above the genetic sequence.
And that it is- the formal definition of epigenetics is "the study of molecules and mechanisms that can perpetuate alternative gene activity states in the context of the same DNA sequence" (Cavalli and Heard 2019) but another way to say it is- the study of molecules and mechanisms interacting with DNA and affecting the expression of the DNA (the turning on and off of genes).
Epigenetics is what causes identical twins with the exact same DNA sequence to have slightly different appearances, such as one having a mole and the other doesn't. One developing cancer at 40 while the other lives cancer free their whole lives. This great article by the Atlantic highlights some interesting twin cases.
Epigenetics also plays a major role in why living organisms age, which has been termed the epigenetic clock (Horvath and Raj 2018). Building on these findings, we can view how to approach and treat age-related disease differently than we have in the past (Parrot and Bertucci 2019).
These mechanisms of aging have been found to be very conserved across species (Lu et al 2021) and therefore studies to increase health and longevity of our animal companions could not only benefit our furry counterparts but also potentially benefit humans.
How can we use epigenetics to estimate the age of an animal?
If you've been exploring epigenetics and it's role with aging, you may have heard the terms chronological vs biological age. These two terms refer to potentially different numbers for an individual so it's important that we understand what each represents and how each is useful in it's own way.
Chronological age
Also known as physical age. This refers to the number of actual years an organism has been alive.
Three of the biggest use cases for chronological age include:
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Forensics- Think about how genetics has revolutionized our ability to catch murders. Crime scenes are covered with genetic clues as to who did it, however, genetics has not been able to tell us the age of someone. When there is not much to go off of, epigenetic age estimation comes in for the win, giving us one more clue (McCord et al., 2019). Fun fact, you can also tell if someone was a smoker, former smoker, or non-smoker from DNA methylation. So now there is two clues.
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Conservation- Conservation of wild animal populations can feel a lot like doing forensic work. It's very important to know age when studying endangered populations and in determining if a population is at risk. Age is an important component of population models which help predict the sustainability of the population. Knowing which animals are of reproductive age or will become reproductive soon are important pieces of information to have. Hence, why chronological age tools are such a hit for this area of science (Beal et al., 2019).
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Adopted animals- There are millions of people world-wide owning dogs, cats, horses, birds... and no doubt other animals, but have no idea how old their pet is!? Sure, they probably have some guess and can place their pet in a life stage category but life stages are long and there are years of error in these estimates. With epigenetic aging, high accuracy similiar to studies in human forensics aging have been developed (Raj et al. 2020; Thompson et al. 2017). Seeing signs and symptoms of a disease can mean something very different for two different aged animals and drastically improve outcomes if properly identified by a vet professional.
Biological age
This refers to how old an individual seems compared to their chronological age. This also refers to the aging that leads to age-related diseases. This biological age component is strongly influenced by the environment and what an individual encounters and experiences throughout it's life time.
Knowing more about this biological age clock can help with improving the health span and longevity of living organisms. So the major use cases here involve measuring how different environmental things from drugs, food, exercise, smoking, etc... affect aging and disease development (Lu et al., 2019).
References
Beal, et al. 2019. “The Bottlenose Dolphin Epigenetic Aging Tool (BEAT): A Molecular Age Estimation Tool for Small Cetaceans.” Frontiers in Marine Science, https://doi.org/10.3389/fmars.2019.00561.
Cavalli, Giacomo, and Edith Heard. 2019. “Advances in Epigenetics Link Genetics to the Environment and Disease.” Nature 571 (7766): 489–99.
Horvath S, Raj K. DNA methylation-based biomarkers and the epigenetic clock theory of ageing. Nat Rev Genet. 2018 Jun;19(6):371-384. doi: 10.1038/s41576-018-0004-3. PMID: 29643443.
Lu 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. 2019. 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.
Lu, A. T. et al. 2021. Universal DNA methylation age across mammalian tissues. bioRxiv,
2021.2001.2018.426733, doi:10.1101/2021.01.18.426733.
McCord, B. et al. 2019. Applications of epigenetic methylatoin in body fluid identification, age determination, and phenotyping. Forensic Sci. International: Genetics Supplement Series. doi:10.1016/j.fsigss.2019.10.061
Parrott BB, Bertucci EM. Epigenetic Aging Clocks in Ecology and Evolution. Trends Ecol Evol. 2019 Sep;34(9):767-770. doi: 10.1016/j.tree.2019.06.008. Epub 2019 Jul 8. PMID: 31296344.
Raj, K. et al. 2020. Epigenetic clock and methylation studies in cats. bioRxiv,
2020.2009.2006.284877, doi:10.1101/2020.09.06.284877.
Thompson, M. J., vonHoldt, B., Horvath, S. & Pellegrini, M. 2017. An epigenetic aging clock
for dogs and wolves. Aging (Albany NY) 9, 1055-1068, doi:10.18632/aging.101211.