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Epigenetic Ageing and the Epigenetic Clock

by Claudia Ghezzou Cuervas-Mons

Recent advances in DNA science, partly driven by the recognised advantages when matched with personalised medicine, are making it easier to peer through the molecular mechanisms that help drive our health and well being. In particular, epigenetic advances are providing an even wider perspective on how our lifestyle and environment can impact our health.

Epigenetics is the turning on or off of our genes, normally by means of tagging certain regions of our DNA. Imagine a highlighter pen (our epigenetics) going through our book of instructions (our DNA) and highlighting whether something was relevant or not. This epigenetic ‘highlighter’ does not alter the instructions in our book (our DNA) but merely magnifies what can or cannot be read, thereby influencing what is ultimately legible. One such epigenetic highlighter is a process called methylation, which adds tags to specific DNA regions as a means ofregulating genes.

These modifications in our DNA have a major role in maintaining the integrity of the genome and turning on and off certain genes due to internal and external cues, and allows the normal functionality of our 3D genome. The modifications are dynamic and reversible, and over a person’s lifetime, many tags will be added or removed.

Nevertheless, when these processes do not run smoothly it can lead to disease. The study of these tags has allowed scientist to generate mathematical models that can predict certain predisposition to disease. Furthermore, the more data that is collected regarding how the epigenetic tagging mechanisms work, the better understood are the tag patterns and whether they imply that things are working adequately or that we should keep some habits on check in order to avoid developing disease.

These complex mathematical models are trained to compare our chronological age to our biological age, the latter being our body or cells’ actual age. These computations collect data based on the levels of methylation tags all around our DNA and alongside complex calculus, give us our estimated epigenetic age. That is our actual molecular age; the age of our cells!

There are many variants of epigenetic clocks, which look at methylation patterns through different perspectives; looking at different cell types, using different algorithms, and many other variables. One such model is Horvath’s clock, which measures the difference of age between methylation patterns obtained from many different tissues (including saliva) and the chronological age. Another one is Hannum’s clock, which focuses on blood samples. Ultimately, these estimates of our molecular age, are footprints of our health and give a good account of the biological changes over our life course. As means of biomarkers, they seem to provide the more accurate estimates, thus enabling better and more robust approaches to disease prevention, disease prognosis, and therapeutics.

As mentioned earlier, methylation tags are dynamic and ever changing and external cues alter whether some areas of our DNA are tagged or not, and in turn control whether things continue to function properly or go awry. Such external factors range from pollution, diet, stressors, oxidants, etc. Therefore, the environment we live in and the lifestyle choices we take have a drastic impact on how these tags are added or removed, influencing potential risks to disease.

But which factors can lead our cells to age more rapidly?

It is quite personal how different factors affect each and one of us. That being said, there are common hallmarks and biomarkers indicative of disease risk that are common to us all. Since we know our DNA instruction book fairly well, it enables studying the effect of the methylation tags in those sites (CpG sites) and how they will affect our internal functions, depending on which instructions they are enabling or blocking. In the same context, it can be studied how environmental factors influence where the methylation tags are put on and consequently what implications it has inside our cells.

Some stressors such as long-term exposure to air pollution have been associated with a slight increase in the epigenetic age. Other examples are smoking, which induces abnormal methylation patterns, thus increasing the risk of tumour growth (the methylation tags are highlighting the wrong instructions). Insomnia and extreme lifestyle stressors also induce methylation changes that eventually lead to detrimental health outcomes.

The good news is that epigenetic alterations are dynamic and reversible. With the correct analysis of our epigenetic scenery and our actual epigenetic clock estimates we can assess how environmental factors affect our internal functionings and we can counteract them by choosing the lifestyle that works best for our health.

How can we delay ageing?

Having a good night sleep is important to slow down your epigenetic ageing, as it has been observed in studies that sleep deprived people tend to have an accelerated clock. Additionally, a healthy nutritious diet, composed of many vegetables and fish, meditating, and avoiding smoking. have also shown to slow down the ageing process.

All in all, epigenetic clocks have become a more precise tool to help us comprehend how our environment and lifestyle truly influences our molecular machinery, which if not looked after properly can lead to disease. It’s an exciting time not only for the scientific community, but for all of us that take interest in healthy leaving, maintaining the integrity of our cellular processes, and preventing disease.

Epigenetic clocks, functioning as biomarkers, can lead to more efficient and personalised therapies, more accurate disease risk factors, and higher chances of preventing and reversing disease.

Claudia Ghezzou is studying as a neuroscientist and is a science communicator

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