Interview with Martin Berlet, CEO of epiAge Germany

Martin Berlet is the managing director of epiAge Germany. In the following interview, we talk to him about the present and future of the epiAge epigenetic age test. He 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 in 2013. It is based on the finding that with increasing age, small molecules attach themselves to the genes, so-called methylations. Horvath identified 353 sites on genes (so-called CpGs) whose methylation showed a good correlation with chronological age.

If these methylations take place at 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". For example, 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 calculate the biological age from this?

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

This reduction of variables has several advantages over the technology used so far. It makes the test more robust.

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

The body is not a mechanical structure whose clock ticks down every second or minute. Epigenetics is influenced by many things. Both in a positive and negative sense.

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, by the way, can be a strong "driver" of the epigenetic clock. Meditation can therefore be just as "healthy" as the right diet.

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

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

We do not ask our clients for their chronological age, so we act completely "blind".

The human ageing process is fundamentally very individual and dependent on various factors.

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

The epiAge test gives you an overview of how quickly or slowly you have aged so far. This can be very different. However, it is known that an accelerated and high epigenetic age correlates with the typical chronic age-related diseases, such as cancer, diabetes, cardiovascular diseases, etc. To potentially detect that early on is, of course, incredibly helpful.

Many of these diseases can be detected/treated at an early stage, or avoided altogether, if one adjusts one's lifestyle accordingly in time, or goes to the doctor.

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

This is also being researched intensively worldwide, and several large companies and investors have identified this area as a lucrative field for the future. And we too have 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 in the foreground for us, because 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 may 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 paper that probably only very few methylations are actually involved in gene silencing. From our point of view, these are the ones to focus on.

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

So we don't really understand epigenetics yet. This also applies to the aging process in particular.

In this context, some researchers postulate the so-called "Hallmarks of Aging" as the cause of ageing. These need to be "repaired". I am not a medical doctor, of course, but I do have an opinion on this. You can probably achieve a lot with this in terms of "repair medicine", but from my point of view it can only be a systemic approach that brings about real rejuvenation.

However, there is evidence that some of the methylations are actually involved in gene expression, while others may have no direct effect on the corresponding genes. This is, of course, tremendously exciting. When you consider that with a reduction in epigenetic age, the body might function a little better again, the health benefits cannot be overstated.

We have already collected long-term tests but also shorter follow-up data. These are very promising, but also very different in design. In one test subject, for example, we measured the effects of a keto diet. After 12 weeks, the subject not only lost quite a few kilos, but reduced his epigenetic age by more than 3 years. That fasting has a positive effect on health has of course been known for a long time, and any doctor will tell you that. In a long-term observation we could observe a steady epigenetic rejuvenation over a period of 480 days with an intervention.

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

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

Martin Berlet: Indeed, an important point. Unfortunately, we experience time and again that not enough importance is attached to the correct saliva output, which can be reflected in a failed test. When releasing saliva, one should make sure not to eat, drink, smoke or brush one's teeth for at least 30 minutes beforehand. Taking substances containing collagen or medications that suppress the immune system can also negatively affect the test.

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

Martin Berlet: Basically, 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, at best, to optimise 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 variant of the epiAge test in the (near) future based on future research findings?

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 adapted as the amount of data increases. But that 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 were able to reduce the effective "waiting time" for the customer by 50 % through optimised processes. That means we are currently at 3-4 weeks. For the future, however, we see further potential to become even faster in this area. Our goal is to reach a value of approx. 12-14 days.

MoleQlar: The epiAge test is a simple saliva test. Doesn't the saliva "break down" over the evaluation period? Who or what do the scientists look 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 the analysis is then extracted from the saliva and prepared for sequencing.

MoleQlar: In a recent study, Mongelli et al. investigated the biological age of 117 COVID-19 survivors and compared it with 144 uninfected volunteers(https://doi.org/10.3390/ijms22116151). The results show a significant increase in biological age in the group after surviving SARS-CoV-2 infection compared to the healthy study participants. Obviously, the SARS-CoV-2 virus has an influence on epigenetics. Can we assume that these changes are permanent? Have similar changes been observed in other bacterial or viral infections?

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

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

How to treat long covid symptoms in the long term is certainly the subject of quite a few 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 with NGS (Next Generation Sequencing) and is no longer based on chip arrays that examine much larger parts of the genome. In the epiAge test, each sample is sequenced three times and, depending on the quality of the sample, several thousand cells are analysed in order to gain the most accurate insight possible into the "epigenetic events". 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 are particularly evident in so-called follow-up tests, where, for example, one wants to monitor an intervention with supplements and its effects on the epigenetic age.

Thank you very much for the informative interview!