Martin Berlet is 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 German-American bioinformatician Steve Horvath developed the first epigenetic age test in 2013 . It is based on the knowledge that as we age, small molecules attach to 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.
Meanwhile, other researchers have also taken up this approach and further developed the “Horvath Clock”. This also applies to 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 digits 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. This region of the genome in which they lie correlates most strongly with chronological age.
This reduction in variables has a number of advantages over the technology previously used. This makes the test more robust.
This is of course a huge advantage for us, because we were already able to “see” how epigenetic age reacts in our own test series. This is generally a fairly dynamic process.
The body is not a mechanical structure whose clock ticks down every second or minute. Epigenetics is influenced by many things. In a positive sense and in a negative sense.
This includes not only physiological factors, but also psychological ones, as has been shown in the past. To put it simply, it is just as important to pay attention to a healthy diet as to avoid stress, which can be a strong “driver” of the epigenetic clock. Meditation can be just as “healthy” as proper nutrition.
MoleQlar: What can users expect from the epiAge test? What information will they receive as a result and what exactly can they do with it?
Martin Berlet: The epiAge test result contains a so-called epiAge score. This is calculated from an algorithm based on the methylations of the 13 CpGs mentioned above. This score is then placed in relation to our comparison cohorts and results in 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 and environment (e.g.b environmental pollution), genetic predisposition as well as habits (especially bad ones such as smoking or excessive consumption of alcohol) and individual lifestyle (e.g.b Nutrition).
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 is associated with the typical chronic diseases of aging, such as cancer, diabetes, cardiovascular diseases, etc. correlated Recognizing this early on is of course incredibly helpful.
Many of these diseases can then possibly be recognized/treated as they develop, or avoided entirely if you adjust your lifestyle accordingly in good time or go to the doctor.
Fortunately, the methylations on the genes are reversible, i.e. reversible, which opens up the possibility of intervention.
There is intensive research into this around the world, and a number of large companies and investors have identified this area as a lucrative future field. And we have already developed interventions that turn back the epigenetic age. With some astonishing results, which we can only describe as anecdotal since we do not conduct any scientific studies ourselves. The health benefits are our priority, 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 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 work that probably only very few methylations are actually involved in so-called gene silencing (i.e. the silencing of genes). From our point of view, this is what we need to focus on.
This is an incredibly complex field and therefore fraught with a number of 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.
So we don't yet understand epigenetics properly. This particularly affects the aging process.
In this context, some researchers postulate the so-called “Hallmarks of Aging” as the cause of aging. These need to be “repaired”. Of course I'm not a doctor, but of course I have an opinion about it. You can probably achieve a lot with this in the sense of “repair medicine”, but in my opinion 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 not have a direct effect on the corresponding genes. This is of course incredibly exciting. When you consider that by reducing the epigenetic age the body may function somewhat better again, 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 designed very differently. For example, we measured the effects of a keto diet on one test subject. After 12 weeks, the person not only lost several kilos, but also reduced their epigenetic age by more than 3 years. Of course, we have known for a long time that fasting has a positive effect on health and any doctor can attest to this. In a long-term observation, we were able to observe constant epigenetic rejuvenation over a period of 480 days with an intervention.
We are currently examining which partner we can best implement 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 sources of error are there when carrying it out What do you have to pay attention to in advance when carrying out the test? (exercise, alcohol, smoking, food intake, ...)
Martin Berlet: An important point indeed. Unfortunately, we often experience that not enough emphasis is placed on the correct release of saliva, which can be reflected in a failed test. When releasing 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 years takes the epiAge test and receives a value of 65 years for her biological age. She then tries to live a healthier life. When does it make sense to repeat the test in your case? And are there interventions that have a particularly large influence on the test result? If so, which interventions are they?
Martin Berlet: In principle, we cannot and are not allowed to make any medical statements about the individual test results.
But the test may give you the impetus to visit a doctor again, or to question your own lifestyle and ideally optimize it.
MoleQlar: As is well known, epigenetics is a heavily researched topic. It is planned to adapt the epiAge test to new findings? Is there perhaps a variant 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 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 were able to reduce the effective “waiting time” for the customer by 50% through optimized processes. That means we are currently at 3-4 weeks. However, we see further potential to become even faster in this area in the future. Our goal is to achieve a value of approx. 12-14 days to arrive.
MoleQlar: The epiAge test is a simple saliva test. If the saliva does not “break down” over the evaluation period? Who or what do the scientists look closely at in the saliva?
Martin Berlet: There is a so-called buffer solution in the test tubes for the saliva sample. If 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. the biological age of 117 COVID-19 survivors and compared it to 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. The SARS-CoV-2 virus obviously has an influence on epigenetics. Can it be assumed 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's the good news. But of course the question of intervention arises.
I have already seen studies that looked at the topic as early as 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 around the world.
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 the chip arrays that examine much larger parts of the genome. In the epiAge test , each sample is sequenced three times and, depending on the sample quality, several thousand cells are analyzed in order to get the most precise insight possible into the “epigenetic process”. . The epiAge test is therefore much more robust and less error-prone than the other tests available on the market, which sequence less often and sometimes examine significantly fewer cells.
The problems with the other tests are particularly evident in so-called follow-up tests, where, for example, you want to monitor an intervention with supplements and their effects on epigenetic age.
Thank you very much for the insightful conversation!
