Slower ageing thanks to epigenetics is the future of personalised medicine and will gather pace in the coming years, says epigenetics expert, Dr. Tomasz K. Wojdacz, MD.

In the 1960s, scientists noticed that the chronological age of a person may differ from the age indicated by epigenetic changes accumulated in the person's DNA. Based on this knowledge, after years of research, they created the epigenetic clock - universal and extremely precise sets of molecular biomarkers of cell ageing.

Now researchers have noticed that some factors accelerate the epigenetic clock, causing a too fast progression of adverse changes in our body, contributing to the development of diseases and shortening life expectancy.

In the future, by manipulating these factors, we will be able to stop ageing and restore it to the level determined by our birth certificate. This is not fiction, it is a matter of the coming years, says Dr. Wojdacz, MD, a professor at Aarhus University (Denmark) and head of the Independent Clinical Epigenetics Lab of the Pomeranian Medical University of Szczecin.

He said: “Each of us has their own chronological age. It exists and cannot be cheated. However, sometimes, quite often even, we age faster than our birth certificate would suggest. And it seems that epigenetics is the major factor responsible for this.

“After all, generally there are no mutations in our cells, the DNA sequence does not change, and yet, if we look at the epigenetic changes that occur in the cells, we often see that their ageing accelerates.”

He continued that epigenetics is the basis of cellular development and differentiation. “Each cell of the body has exactly the same DNA, and yet the heart is different from the liver, and the muscle from the eye. So there must be mechanisms that make it possible to read DNA information in various ways, in a way specific to a given cell. These mechanisms are called epigenetics. It activates certain genes while muting others. Because of epigenetics, the cell does what it is supposed to do in a given place and a given moment. Epigenetics is something that turns genes on and off in order to properly specialize every cell.”

The human body begins to age from the moment of conception. Many factors are responsible for this, but the one that has been of particular interest to scientists in recent years is the process called DNA methylation - one of the basic epigenetic mechanisms that determines the functioning of the cell. Simply put, the methylation marks genes that the cell does not need and keeps them in a inactive state. If there are methylation changes, genes that should not work in a given cell begin to work, and those that are needed are muted. The older the body, the more changes in the DNA methylation occur, which contributes to the initiation of adverse processes and the development of age-related diseases.

When the body works properly, and in addition it is in optimal conditions, epigenetic age is consistent with chronological age. However, it sometimes happen that the former begins to accelerate, causing the body to age faster than it should.

Dr. Wojdacz said: “Many years ago, scientists noticed that based on the number of epigenetic changes in specific DNA fragments, we can estimate the age of a person. The epigenetic clock was developed. It is a set of molecular markers that can be used to measure age, and which is based on DNA methylation levels.

“In short, we analyse methylation changes in the cell, and we use bioinformatic tools and artificial intelligence to calculate the epigenetic age of a given person. We then correlate this value with actual age. And if they match, we consider the person to be in a good general condition. And if the two values differ significantly, i.e. there are more epigenetic changes than the birth certificate would suggest, it means that something wrong is happening in the body.”

The scientist explains that there are about 26 million places in the genome where methylation can occur. Although, because of the complexity and expense, they are not all tested, a very effective technology based on micro-matrices makes it possible to measure methylation changes in about 800,000 places at once.

Dr. Wojdacz said: “The result of such a test is compared with information about a specific person to checks if there are any correlations between epigenetic changes and the person's age. As a result, we get a map of places that are actually related to the ageing of the body. There are several dozen to several hundred such places, depending on the tissue and the 'clock' that is used. To sum up: epigenetic changes are a biomarker of ageing.”

He continued: “We do know for sure that if the cell has already gone through several division cycles or is in very adverse environmental conditions, then its age counted according to methylation changes is fundamentally different from the one indicated by its +date of birth+.

Adverse environmental conditions are the factor that moves the hands of the epigenetic clock the most. Most studies show that a healthy lifestyle, i.e., physical activity, the right amount of sleep and a healthy diet, brings epigenetic age closer to chronological age. And vice versa - a wrong lifestyle causes the greatest discrepancies.”

According to Dr. Wojdacz the most important thing is that knowing about the existence of such correlations and by knowing the factors that strongly accelerate molecular ageing, we can start to search for ways to reverse adverse changes. Epigenetic changes differ from genetic ones in that they can be easily undone.

He said: “There are even studies that show that in people whose epigenetic age significantly exceeded their actual age, after changing several key lifestyle aspects these values began to equalise. And it happened quite quickly.

“Genetics is very stable, epigenetics is fluid. Epigenetic changes arise and can be reversed because simple enzymatic processes are responsible for them. What's more: they can occur naturally, but they can also be induced. That is why it is a great field for all kinds of medical interventions.

“This means that by studying a large group of people and comparing epigenetic changes in their cells with their age, we can create a kind of guide showing what lifestyle behaviours lead to faster epigenetic changes, and thus faster ageing. And we also immediately know what behaviours or interventions will reverse these changes, and thus restore normal ageing processes. We can even anticipate human life expectancy based on the person's epigenome. Of course, we will not stop time and ageing, but we can restore them to the optimal state.”

According to the expert, in the future this will definitely translate into practical clinical applications. On the basis of a blood sample, doctors will be able to determine who is more susceptible to certain diseases or whose life expectancy is shorter than it should be. And this can be modulated by giving appropriate recommendations to patients.”

Until recently, it was thought that structures called telomeres have the greatest impact on the ageing process. These are DNA fragments located at the ends of chromosomes, performing protective functions during cell divisions. 

Wojdacz said: “From year to year, however, it turns out that telomeres do not have such a big role in the regulation of ageing. It has been noticed that some cells during their lives divide very quickly and still have long telomeres; others almost never divide and their telomeres are short. So the assumption that we will be able to anticipate life expectancy based on the length of telomeres appears not to be confirmed.

“Epigenetic age is at the opposite pole - its correlation with ageing and life expectancy is becoming more and more clear. The connection between chronological and epigenetic age is much stronger and more predictable than between age and telomeres.

“When it comes to factors that induce epigenetic changes related to ageing, for now it has been confirmed that they are: sleep, healthy eating, an adequate level of physical activity.

“They were easy to confirm because research can be conducted on huge groups of people. Unfortunately, is much more difficult to verify the less common factors that potentially accelerate ageing, because it is not easy to complete a sufficiently large group. A sufficiently large group means thousands or even hundreds of thousands of people. Only such values allow us to confirm a given correlation beyond doubt. So even if we see that the age of a person is associated with some less obvious factor, this correlation is weak and cannot be the basis for recommendations.”

He continued: “Research on the links between epigenetic changes and age is a field that has exploded in recent years. Many research groups in the world focus on. This is the branch of science that will allow us to predict the life expectancy of people, predict the risk of diseases, determine what environmental factors are harmful to us.

“For now, this is science, learning, but practice will follow soon. The strength of this association is huge. We see it, we understand it, but in order to be able to recommend something for clinical applications, research must be repeated multiple times on huge populations. And currently the biggest problem of this field of science is to find sufficiently large groups. This is a problem of all personalised medicine.”

He added, however, that we are already at the moment of history when we are really approaching the critical point when it comes to the amount of data required to calculate and with a high degree of certainty recommend specific lifestyle changes or even treatment. 'The larger the group of patients examined, the closer we are to such recommendations. And we are really approaching this level. There is already so much information in some databases that we can predict some diseases, states, etc. with near-certainty.”

“For now, our main challenge is to learn to restore epigenetic age to chronological age.

“Will we go a step further in the future and be able to rejuvenate people? We do not know at this point, but such research will certainly appear. There are premises for it. Take this curious fact, confirmed in dozens of different studies, that laboratory animals on a low -calorie diet live longer. This means that we have a potential factor that slows down the ageing process. But this is obviously only speculation. For now, we focus on stopping excessively fast ageing,” he said. 

PAP - Science in Poland, Katarzyna Czechowicz

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