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Interview with Martin Berlet, CEO of epiAge Germany
Interviews Magazin

Interview with Martin Berlet, CEO of epiAge Germany

Martin Berlet is Managing Director of epiAge Germany. In the following interview we talk to him about the present and future of epiAge epigenetic age testsHe also provides exciting insights into epigenetic research.

MoleQlar: What is the scientific background of the epiAge test?

Martin Berlet: The first epigenetic age test was developed by the German-American bioinformatician Steve Horvath Developed in 2013. It is based on the knowledge that as we age, small molecules, known as methylations, attach themselves to genes. Horvath has identified 353 locations on genes (known as CpGs) whose methylation has shown a good correlation with chronological age.

If these methylations occur in so-called promoter regions of a gene, this can, for example, lead to this gene being silenced.

In the meantime, other researchers have also taken up this approach and further developed the “Horvath Clock”. This includes Professor Moshe Szyf from McGill University in Montreal, who developed the epiAge test.

MoleQlar: The epiAge test is based on the evaluation of 13 DNA methylation sites. Why are there exactly these 13 sites and not more or less? And how do you then calculate the biological age?

Martin Berlet: Prof. Szyf was able to show that it is sufficient to use only these 13 CpGs. The region in the genome in which they are located correlates most strongly with chronological age.

This reduction in variables has several advantages over the technology used previously. It makes the test more robust.

This is of course a huge advantage for us, because we were able to "see" how the epigenetic age reacts in our own test series. This is generally a very dynamic process.

The body is not a mechanical structure whose clock ticks down every second or minute. Epigenetics is influenced by many things, both positively and negatively.

This includes not only physiological factors, but also psychological ones, as has been shown in the past. Put simply, it is just as important to pay attention to a healthy diet as it is to avoid stress, which can be a strong "driver" of the epigenetic clock. Meditation can therefore be just as "healthy" as a proper diet.

The mastermind behind the epiAge test - Prof. Moshe Szyf from McGill University in Montreal

MoleQlar: What can users expect from the epiAge test? What information do they receive as a result and what can they actually do with it?

Martin Berlet: The epiAge test result contains a so-called epiAge score. This is calculated using an algorithm based on the methylation of the 13 CpGs mentioned above. This score is then put in relation to our comparison cohorts and gives the expected biological age.

We do not ask our customers about their chronological age, so we act completely “blind”.

The human aging process is fundamentally very individual and depends on various factors.

Biological age is an expression of a variety of aspects of personality, as well as the environment (e.g. environmental pollution), genetic predisposition, habits (especially bad ones such as smoking or excessive consumption of alcohol) and individual lifestyle (e.g. nutrition).

The epiAge test gives you an overview of how quickly or slowly you have aged so far. This can vary greatly. However, it is known that an accelerated and high epigenetic age correlates with the typical chronic diseases of aging, such as cancer, diabetes, cardiovascular diseases, etc. Being able to detect this at an early stage is of course incredibly helpful.

Many of these diseases can possibly be detected/treated at an early stage, or even avoided altogether if you adjust your lifestyle accordingly or go to the doctor in good time.

Fortunately, the methylations on the genes are reversible, which opens up the possibility of intervention.

Intensive research is being carried out on this worldwide, and a number of large companies and investors have identified this area as a lucrative field for the future. We have also already developed interventions that turn back the epigenetic age. Some of the results are astonishing, but we can only describe them as anecdotal, as we do not conduct any scientific studies ourselves. The health benefits are our main focus, as to date it has not been fully researched what exactly the various epigenetic clocks measure.

So it makes no sense for us to recommend a supplement that might show particularly impressive results in epigenetic age tests that work with many CpGs. As long as this is not accompanied by an improvement in health, it is of little use to us.

Prof. Szyf has just shown in a new study that probably only very few methylations are actually involved in so-called gene silencing. In our view, these are the ones we need to focus on.

This is an incredibly complex field and therefore fraught with difficulties. We understand epigenetics as a type of software that controls the function of cells. However, how this software really works has not yet been sufficiently researched.

We don't yet fully understand epigenetics. This particularly applies to the aging process.

In this context, some researchers postulate the so-called “Hallmarks of Aging“ as a cause of aging.  This needs to be "repaired". I am not a doctor, of course, but I do have an opinion on the matter. You can probably achieve a lot with this in the sense of "repair medicine", but in my view, only a systemic approach can bring about real rejuvenation.

However, there is evidence that some of the methylations are actually involved in gene expression, while others may not have a direct effect on the corresponding genes. This is of course incredibly exciting. When you consider that reducing the epigenetic age may make the body function a little better, the health benefits cannot be overestimated.

We have already collected long-term tests as well as shorter follow-up data. These are very promising, but also very different. For example, we measured the effects of a keto diet on one test subject.After 12 weeks, the person had not only lost several kilos, but had also reduced their epigenetic age by more than 3 years. It has long been known that fasting has a positive effect on health and any doctor can confirm this. In a long-term observation, we were able to observe a steady epigenetic rejuvenation over a period of 480 days with an intervention.

We are currently examining which partner we can best work with to translate our findings into a rejuvenation strategy that we can also make available to others.

The epiAge epigenetic age test measures your biological age.

MoleQlar: What is important when carrying out the test so that it actually works and determines the "correct" biological age? In other words: What sources of error are there when carrying out the test? What do you have to pay attention to in advance when carrying out the test? (Sport, alcohol, smoking, food intake, ...)

Martin Berlet: This is actually an important point. Unfortunately, we often experience that not enough importance is placed on the correct saliva sample, which can be reflected in a failed test. When giving saliva, you should make sure not to eat, drink, smoke or brush your teeth for at least 30 minutes beforehand. Taking substances containing collagen or medications that suppress the immune system can also have a negative effect on the test.

MoleQlar: Let's look at an example: A woman with a chronological age of 50 takes the epiAge test and receives a result of 65 years for her biological age. She then tries to live a healthier life. When does it make sense in her case to repeat the test? And are there interventions that have a particularly big influence on the test result? If so, what are they?

Martin Berlet: In principle, we cannot and are not allowed to make any medical statements about the individual test results.

However, the test may give you the impetus to visit a doctor again, or to question your own lifestyle and, ideally, optimize it.

MoleQlar: Epigenetics is known to be a highly researched topic. Are there plans to adapt the epiAge test to new findings? Will there perhaps be a version of the epiAge test in the (near) future that is based on future research results?

Martin Berlet: Indeed. We are currently testing an epiSmoke and a skinAge test. The epiAge test is of course also constantly being "improved" and the mathematical model is being adapted as the amount of data increases. But this is a completely normal process.

MoleQlar: The epiAge test takes an average of 6-8 weeks. What happens during this time? Why is the waiting time for the result “so long”?

Martin Berlet: We have been able to reduce the effective "waiting time" for the customer by 50% through optimized processes. This means that we are currently at 3-4 weeks. However, we see further potential for becoming even faster in this area in the future. Our goal is to reach a value of around 12-14 days.

MoleQlar: The epiAge test is a simple saliva test. Doesn't the saliva get "broken" over the evaluation period? Who or what exactly are the scientists looking at in the saliva?

Martin Berlet: The test tubes for the saliva sample contain a so-called buffer solution. When the saliva mixes with it, the sample is preserved for a longer period of time. The DNA required for analysis is then extracted from the saliva and prepared for sequencing.

MoleQlar: In a recent study Mongelli et al. examined the biological age of 117 COVID-19 survivors and compared it with 144 uninfected volunteers. The results show a significant increase in biological age in the group after recovering from SARS-CoV-2 infection compared to the healthy study participants. Obviously, the SARS-CoV-2 virus has an influence on the epigeneticsCan we assume that these changes are permanent? Have similar changes been observed in other infections of a bacterial or viral nature?

Martin Berlet: Methylations are in principle reversible, that is the good news. But of course the question of intervention arises.

I have already seen studies that dealt with this topic in 2017, long before COVID 19 appeared in the world. There is therefore evidence that coronaviruses, and COVID 19 is just one of them, remodel the methylation environment of their host cells.

How to treat Long Covid symptoms in the long term is certainly the subject of several research groups worldwide.

MoleQlar: And one last question: What makes the epiAge test unique? What sets it apart from competing products?

Martin Berlet: The epiAge test is carried out using NGS (Next Generation Sequencing) and is no longer based on chip arrays that examine much larger parts of the genome. Each sample in the epiAge test three times sequenced and, depending on the sample quality, several thousand cells are analyzed in order to gain as precise an insight as possible into the "epigenetic processes". The epiAge test is therefore much more robust and less prone to errors than the other tests available on the market, which sequence less often and sometimes examine significantly fewer cells.

The problems of the other tests become apparent especially in so-called follow-up tests, where one would like to monitor, for example, an intervention with supplements and its effects on epigenetic age.

Thank you very much for the insightful conversation!

Useful links

A computational solution for bolstering reliability of epigenetic clocks: Implications for clinical trials and longitudinal tracking –  https://www.biorxiv.org/content/10.1101/2021.04.16.440205v1

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