Dr. Moshe Szyf from EpiMedTech Global in Singapore discusses a research paper he co-authored that was published in Volume 17, Issue 1 of Aging (Aging-US), entitled “EpiAge: a next-generation sequencing-based ELOVL2 epigenetic clock for biological age assessment in saliva and blood across health and disease.”
Behind the Study is a series of transcribed videos from researchers elaborating on their recent studies published by Aging (Aging-US). Visit the Aging (Aging-US) YouTube channel for more insights from outstanding authors.
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I am Moshe Szyf. I am the founder, chairman, CEO, and CSO of EpiMedTech Global. It’s a company that is dedicated to harnessing the epigenome to develop tools for early detection of disease. And that, of course, led me to the biological clock, perhaps one of the best measures of our biological state, which could guide us in changing lifestyles and habits to improve our health. However, the clocks that exist today were all based on many CPG sites, and based on array detection methodology because of the abundance of CPG sites that form the clock. And that was not very practical as a tool for the public.
And there were two issues with the prevailing clock when we started. First, they were all blood-based, second, they were all array-based, and third, they were all based on numerous CPG sites. And the question that we asked, can we develop a robust tool to measure APH that doesn’t require that number of CPG sites, doesn’t require arrays, and could be done on saliva? Therefore one can send a kit to the person and can send us the saliva back, and it could be tested on these samples.
This led to the paper that I’m going to talk to you today, titled “EpiAge: a next-generation sequencing-based ELOVL2 epigenetic clock for biological age assessment in saliva and blood across health and disease.”
We wanted to find the minimum region in the DNA that could provide us the highest accurate information on the biological age and therefore could be amenable to targeted high throughput, next-generation sequence and avoid the pitfalls of arrays as a clinical tool. When we examined the sites that were previously described as clock cells, as well as other sites across the genome, we discovered that it’s what region that has such a strong statistical correlation with age that trumps everything else.
And we asked the question, could this unique region be sufficient and therefore could be further developed into a next generation targeted high triplet test? The thorough examination of publicly available data suggests that even one CG in that region of the low L two gene, which was known before as a gene that correlated with aging, had the same statistical strength as the available clocks. That gave us some comfort, and it was extremely surprising that you can achieve the same results with one or two CGs and you don’t actually need the rest of the CGs to inform you about biological age.
The second question we asked, would it work in saliva and how well would it work? Again, here we addressed by data publicly available data in saliva, and to our surprise, these sites performed as well in saliva as they performed well in blood. And at that point we asked the question, can we develop a next generation sequencing test that could be multiplex targeted high throughput? So hundreds of tests could be done the same time, and we’ll provide accurate information on the biological age. We have done so and we have used this next generation sequencing test to assess its performance. We applied a very stringent requirement because we’re using next generation sequencing tests that is high. We could do triplicate tests per sample and define the error in the test and discover that we could develop a test that could be highly accurate.
We also demonstrated that this region is highly sensitive to health conditions. For example, we previously demonstrated that our tests can differentiate between people infected with CMV and those are knots and that people infected with CMV are older biologically than people who are not. We could also show that people infected with HIV have a higher biological age than others, which was shown with other clocks, but our clock performed as well. The most interesting and the most surprising one, that actually the best correlate of age acceleration is not a physical condition, but actually stress and current stress became the best or the strongest event that alters the biological clock.
Again, here we could show that this clock functioned as well, if not better and more sensitive to current stress as other clocks. So what can we do next? Obviously, the big question is how could the physician use this tool to guide the health maintenance of the patients? How well does this clock correlate with changes in the state of the body that could be detected earlier than with other tests and guide interventions that could block deterioration in the health center because of the ease of the test? It could provide a fantastic tool for health providers to monitor longitudinally and along the time course the changes in a biological state of their patients and to utilize it for improvement of health. Obviously, we don’t have the answers to that. We still don’t understand how to incorporate the FPH test in clinical practice, but this will be an important challenge. We believe, although the evidence is not fully there, but we believe that it has a huge potential for guidance of health maintenance.
Of course, the other question is how well would this function at a consumer level where a person could use this to guide lifestyle and other changes that the person can do to improve their own health? For this, we need a lot of people who are followed longitudinally with this things and also collecting other data and analyzing the impact, the changes in lifestyle have on the biological age as well as measuring how the biological age actually tells us about other issues that are involved with the health of the person.
Another issue that we are very eager to understand is how useful our test is in psychiatry and psychological practice because we saw that the test census very well at current stress, but it provide the mental health provider with a tool to assess with a very proximal test the improvement in a patient’s mental health and to alert the health provider for changes in the mental health status that require attention. So there’s a lot to be done, but we hope that once we have such an accurate and robust and hydrobot an easy to use tool, we will get important answers that hopefully will help improve health maintenance or physical and mental health.
You know, of course, this paper could not have happened without the brilliance of some of our scientists. The first author, David (Cheishvili), the team that worked on the paper at McGill, the other researchers provided the important clinical material and our thanks to the databases where people share data that allows other people like us to derive interesting results and to save resources to the general medical community. Thank you.
Click here to read the full study published by Aging (Aging-US).
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Aging (Aging-US) is an open-access journal that publishes research papers bi-monthly in all fields of aging research and other topics. These papers are available to read at no cost to readers on Aging-us.com. Open-access journals offer information that has the potential to benefit our societies from the inside out and may be shared with friends, neighbors, colleagues, and other researchers, far and wide.
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