Put your lab coats on folks.

Epigenetics
is the study of molecules and mechanisms that interact with the DNA
sequence and affect what genes are turned on and off.

For
example, if your genes are the cookbook, epigenetics is the chef
choosing what they are actually going to use out of that recipe for
today's meal. If you spend anytime cooking in the kitchen, you also know
that there are a lot of other factors that are going to play a role in
how the end meal comes out. Those other factors in our real life
scenario would be the environment- which could be food, exercise,
toxins, the microbiome, temperature... just about anything.

Here are a couple great articles that are great introductions to epigenetics:

 "What is epigenetics?"

"Epigenetics 101: a beginners guide to explaining everything" 

A
lot of what we know about epigenetics has come from twin studies. With
twins, we can see just how much is determined by epigenetics vs the
underlying genetic code because twins have the same genetic code.

This great article by the Atlantic highlights some interesting twin case studies. 

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
proactively instead of reactively like 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 do we estimate age from a mouth swab?

Glad you asked!

We quantify an epigenetic molecule called DNA methylation across your pet's genome to calculate their chronological age. We've chosen the most correlated markers to age that are not being affected by environmental factors (unlike biological age which focuses on these noisy markers).

If you've been exploring epigenetics and it's role with aging, you may have heard the terms chronological and biological age. These two terms refer to potentially different numbers for an individual's "age" so it's important that we understand what each represents and how each is useful in its 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: 

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 there's at least two epigenetic clues we can get from a crime scene. 

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). 

​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. For example, a person might be 33 years old, but due to lifestyle choices, has a biological age of 45 meaning their health is bad. You can probably see how this biological age is the kind of age that influences someones potential to develop an age-related disease.

Biological age is strongly influenced by the environment. Anything from where you live, what you eat, what kind of physcial activity you get... and this is the same for any organism including our pets.

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). 

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 clockfor dogs and wolves. Aging (Albany NY) 9, 1055-1068, doi:10.18632/aging.101211.

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