A Primer on Epigenetic/Biological Clocks

James Kay

April 29, 2022

We’ve all done our share of clock-watching in our daily lives, whether it be anxiously waiting for a flight or impatiently waiting until we finish work. It may therefore be unsurprising that doctors and medical researchers do the same thing… but what may surprise you is the type of clock that they’re doggedly watching.

These medical professionals aren’t watching any old clock, no, they’re watching the body’s internal clock, otherwise known as the epigenetic, or biological clock. In this blog post, we’ll be exploring the concept of the epigenetic clock- otherwise known as the biological clock- and we’ll cover what they are, how they work, and, most importantly, what questions they can answer.

So what are epigenetic/biological clocks?

It sounds strange, but people can be a different age from someone the same age as them. In short, your chronological age is different from your biological age. For example, someone can chronologically be 46 (i.e. they have lived on Earth for 46 years) and they can possess a biological age of, say, 54. How does this happen? Well, some people age quicker than others due, largely, to lifestyle factors. This is because factors such as our daily stress, the amount of sleep we get, and our diet all impact how our body functions. So, epigenetic clocks are indicators that have been developed over the last decade by doctors to gauge someone’s biological age (‘bioage’) or inner age.

The first (and best known) biological clock was developed by Dr. Steve Horvath in 2013. Back in 2011, he and his twin brother had participated in a study examining epigenetic markers in saliva. When analyzing the data, he found that DNA methylation (more on this later) could predict a person’s age in years, with a variance of roughly five years on average. Naturally, Dr. Horvath realized that this had massive ramifications for the measuring of the body’s internal biological age.[1]

There are now ten biological clocks measuring how humans age, ranging from the Horvath clock to DNAm PhenoAge, and there are hundreds more used for other purposes. For example, the DNAm PhenoAge clock determines phenotypic age, which, in essence, judges that you are 9% more likely to develop a serious illness for each year you are older than you are chronological.[2]  

In short, epigenetic clocks are medical yardsticks that have recently been developed for the purpose of measuring our biological age and our overall risk of mortality.

So how do they work?

The exact methodology and metrics tracked behind each clock can vary, but the principle remains largely the same. Some of them have even been developed using DNA data sets to develop a neural network that is then fed through a deep learning program to determine which sets of methylated DNA contribute to biological aging.[3] Very cutting-edge stuff!

As mentioned above methylated DNA is the cause of biological aging, despite the methodology behind the development of the clock, but why is this the case? Methylation, in a chemical sense, is the adding of a methyl group of atoms to a molecule. This changes how the proteins of the molecule interact with other proteins, which in turn impact how the molecule interacts with other molecules. Our DNA is governed by an epigenome- essentially a biological controller of how our genes ‘express’ themselves.

The only difference between a liver cell and a brain neuron is that this epigenome tells these genes which job to do by ‘turning off’ certain pre-programmed functions. However, as mentioned above, as our DNA naturally becomes more methylated over the course of our lives these genes begin to change how they interact with their surrounding genes… and this contributes to aging and, sometimes, our risk of illness.

This methylation occurs naturally as we age but it can also depend largely upon our lifestyle. If someone smokes heavily, for example, then certain genes will become highly methylated while others will conversely become less so. Stress, heavy drinking, a bad diet, and a lack of sleep- all similarly impact our DNA methylation levels.

What can biological clocks be used for in the future?

A significant amount of research still needs to be done in this field, as questions remain. However, a number of studies have emerged that suggest DNA methylation can be managed. Unlike a chronological clock, the good news is that it seems possible that the biological clock can turn back time. A clinical trial comprised of randomized individuals found that, according to the Horvath clock, individuals on the trial who lived a healthy lifestyle were 3.23 years younger than those in the control group.[4] This trial is the first that has demonstrated that we can reverse biological aging through living a healthy lifestyle (in the study, moderate exercise, breathing exercises for stress, and a diet rich in methyl donor nutrients and polyphenols were all assigned to those participants, not in the control group).

Another study has found that there is a correlation between a high BMI and older biological age.[5] A further study found that eating a Mediterranean-style diet, with a particular amount of olive oil and nuts, reversed methylation of the body’s intermediate metabolism, diabetes, inflammation, and signal transduction.[6] Definitely a case for moving to that part of the world!

Epigenetic clocks are already, increasingly, being used to accurately gauge an individual’s likelihood of falling ill (such as the DNAm Phenoage) and also as a gauge as to how we can mitigate that risk by demonstrating, using hard data, the benefits of living a healthy lifestyle (such as the 3.23 gain mentioned above). When presenting individuals with the fact that they will be younger by a demonstratable margin, they will be more motivated to make healthier choices because the benefits of those choices will just be so much more tangible.

As the science of developing epigenetic clocks becomes more advanced, it is likely that even more accurate and wide-ranging figures can be provided to the public. Imagine a world where cigarette packets have an exact figure of how many days or weeks people are, on average, aging themselves per pack- it may not be that far away!

In closing

The development of epigenetic clocks is a very promising development in the biomedical field that solves a problem that has plagued the field for decades- how to measure biological aging. These epigenetic clocks also present future benefits to the wider public as they can illustrate to us just how beneficial our healthy choices are… and how detrimental our less healthy choices can be.

If you’re interested in how an app may work that could help you track how these choices are benefitting you, then click here.

Otherwise, for more interesting posts about biomedicine and longevity, make sure to keep checking this blog and sign up for our socials, Twitter and Telegram.

[1] Horvath, S., “DNA methylation age of human tissues and cell types”. Genome Biol. 2013;14(10).

[2] Levine, Morgan E et al. “An epigenetic biomarker of aging for lifespan and healthspan.” Aging vol. 10,4 (2018): 573-591.

[3] de Lima Camillo, L.P., Lapierre, L.R. & Singh, R. A pan-tissue DNA-methylation epigenetic clock based on deep learning. NPJ Aging 8, 4 (2022).

[4] Fitzgerald KN, Hodges R, Hanes D, Stack E, Cheishvili D, Szyf M, Henkel J, Twedt MW, Giannopoulou D, Herdell J, Logan S, Bradley R., “Potential reversal of epigenetic age using a diet and lifestyle intervention: a pilot randomized clinical trial”. Aging (Albany NY). 2021

[5] Quach A, Levine ME, Tanaka T, Lu AT, Chen BH, Ferrucci L, Ritz B, Bandinelli S, Neuhouser ML, Beasley JM, Snetselaar L, Wallace RB, Tsao PS, Absher D, Assimes TL, Stewart JD, Li Y, Hou L, Baccarelli AA, Whitsel EA, Horvath S., “Epigenetic clock analysis of diet, exercise, education, and lifestyle factors”. Aging (Albany NY). 2017 Feb 14;9(2).

[6] Arpón A, Milagro FI, Razquin C, Corella D, Estruch R, Fitó M, Marti A, Martínez-González MA, Ros E, Salas-Salvadó J, Riezu-Boj JI, Martínez JA. Impact of Consuming Extra-Virgin Olive Oil or Nuts within a Mediterranean Diet on DNA Methylation in Peripheral White Blood Cells within the PREDIMED-Navarra Randomized Controlled Trial: A Role for Dietary Lipids. Nutrients. 2017 Dec 23;10(1):15.