Richard Jacobs: Hello. This is Richard Jacobs with the future tech and future tech health podcast. I have Tom Stubs, the CEO of Chronomics.com. We were talking about epigenetic testing to show how your lifestyle and environment affect your DNA and give you the tools to become healthier and to help yourself, which is super interesting. So Tom, thanks for coming.

Tom Stubbs: No, thank you for having me on the show, Richard and pleasure to be here.

Richard Jacobs: I don’t know if a lot of people know, but what is epigenetics, I know people thinking about DNA and their genes, but tell me a little bit about epigenetics, what is that?

Tom Stubbs: Yeah, absolutely. It’s a great question. Which we actually get a lot, so genetics as many of us familiar with is that information we get from our parents and his ruling over us from birth governing whether we’re going to have, for instance, blue eyes or curly hair or a bit risk for certain inherited genetic diseases. But there are also people on the planet share the exact same genetic material, so identical twins. And yet there are many instances where one twin may get sick, for instance, developing some sort of cancer. The other one worked. And the question is how does this happen? And the answer is epigenetics, which is the science of how your DNA is controlled and how it’s affected by environment and lifestyle. So from birth factors such as smoking, sleep, and stress or effecting is epigenetics and dictating the traps that our life is heading down. And what’s exciting is that unlike that genetic information that’s fixed from birth, epigenetics is dynamic, which means that if we find out about these things early enough, we can change tracks to avoid future of health.

Richard Jacobs: Yeah. So I was wondering, so epigenetics is the changes of expression of our genes, and they’ve heard of what’s called methylation and acetylation. So can you talk about a little bit about epigenetics, what’s actually happening to wear genes and then maybe a couple of the ways that it happens?

Tom Stubbs: Yeah, absolutely. So epigenetics is really a catch-all term for a whole host of epigenetic mechanisms that we have in ourselves and as you rightly said, these epigenetic mechanisms are there to ensure the within specific cell types throughout our body. Specific sets of genes are expressed and others are silenced and that really is responsible for defining the cell types that make us up. So if we didn’t have epigenetics, we’d be nothing more than a blob of cells in a dish, if you like. In terms of different epigenetic mechanisms, as I mentioned, you correctly said there are things such as DNA methylation, which is the archetypal epigenetic modification that mammals are found on DNA. When there’s a C based or C letter followed by a G based or G letter. This methylation historically has been associated with the silencing of genes, over, we’re now starting to understand that its function is much more complex than that. And this is actually the epigenetic modification that we use chronomics to define our epigenetic indicators for different environment and lifestyle components. In addition to that, there are modifications to histone marks. So histones, proteins that your DNA is wrapped around and these histone proteins have tails and these tails can be what we call post transnationally modified so they can have different chemical tags placed on them and these tags have diverse sets of functions. Some of the modifications on these tags are also associated directly with DNA methylation levels. So the whole thing is working together. And then there are other types of modification and other types of mechanisms. For instance, looking at different types of RNA that are responsible for and making sure that even though even if a gene is expressed, it cannot go on to make, for instance, proteins. But then power the cell. So this is the whole host of mechanisms that are working in concert to ensure that our cells are functioning properly and we’re staying healthy and it’s happening all the time.

Richard Jacobs: The epigenetics appears to be the adaptation of our master template or DNA that’s affected by the exercise, the food we eat, the environmental conditions. It’s always changing us and adapting us to our conditions throughout our lives.

Tom Stubbs: Yeah, absolutely. Within different parts of our bodies, we need to adapt in different ways and there are numerous examples now of how epigenetics is enabling that adaptation, whether it be looking at, for instance, different muscle cell types and looking at how they respond, following exercise regimes over prolonged periods of time or whether that be, perhaps in less positive settings where for instance, exposures could influence us in a potentially negative manner. For instance, upon smoke exposure when we get epigenetic changes they are associated with changes in gene expression and increased risk of developing things such as lung cancer and heart disease. So there’s really a whole host of adaptation that our body’s trying to do. And that adaptation is essentially maintained using epigenetic mechanisms. But there are also many instances where, well epigenetics is actually being affected by negative environmental and lifestyle influences as well.

Richard Jacobs: You know people are familiar with blood tests, obviously in looking at iron levels and you know, vitamin D, etc. How do you look at methylation or acetylation or the state of someone’s epigenetic profile and how do you look at overtime and see changes?

Tom Stubbs: Yeah, great question. So the way we do chronomics is we send customers a saliva testing kit that they turn, provide their sampling, we come to them their own home. They then send that back in a prepaid envelope to our labs. We then extract DNA from those samples. And importantly, we then are able to modify that DNA samples so that we can look at these epigenetic marks on DNA, DNA methylation marks that we mentioned earlier. And then we create what we call a library. But essentially a way for us to read and see that information and then we sequence it. And what we get back is a whole bunch of epigenetic inflammation on millions of positions throughout the genome. And this information we then use and process through our custom pipelines and algorithms and machine learning workflows to define these epigenetic insights on an online platform and interface that our customers can then engage with to understand more about how environment and lifestyle are affecting their health. And also to engage with a health team to improve their health over time, should they wish.

Richard Jacobs: So what have you seen from the people that you’ve profiled? What jumps out at you when you do one profiling? What things can you see that are affecting you epigenetically?

Tom Stubbs: Yeah, great question. So it really depends on the person, their lifestyle and the environment that they are in. To give some examples of some interesting situations we’ve had. We’ve had some people come in who’ve never smoked in their lives and are actually even athletes, you know, and they come in, they provide the epigenetics sample and what we see is that actually they have really elevated smoke exposure levels and you start saying, okay, how could this be they are athlete, they are training a lot, they’re working, working out, very conscious of the environment and lifestyle and well it turned out in some of these cases that actually because of the environment that they were performing in, they were getting exposed to really high levels of smoke exposure and this has made them much more conscious of the environment in which they’re engaging in. I’m much more observant of what’s affecting them around them. In the same token, we’ve also had people who I’ve had severely elevated biological ages, so biological age as measured by epigenetics is the gold standard for understanding whether you’re at risk of age-related diseases and also all-cause mortality. And from that measure, you can then dive down to try and understand why you have such an elevated biological age for instance and what we’ve seen in many people actually, particularly here in London is that a large amount of that increased elevated biological age relative to chronological age is due to mental health factors. So things like stress, like anxiety starting to affect these people at a biological level, at the molecular level, at the DNA level. And that’s been really interesting to see and be able to work with those people through our health teams on how to enable them to improve their health, while still enjoying what they enjoy and working at the level that they want to work.

Richard Jacobs: So you’re getting information on somebody and they’ll get the information, what can they do about it? How do you have any sense of how hard it is to change yourself epigenetically if someone is exposed to a lot of smoke for some reason, they’re predisposed to having a hard time with it. How do they undo it? You know, epigenetic changes do not, well, some are permanent, and some are not. I would guess, I don’t know if we know which ones are, but how do we modulate any of this?

Tom Stubbs: Yeah, no, but that’s a great question. So what we do know is that through a number of academic studies that have been done is that it is possible to modify epigenetic signatures if you like over time. So studies have been conducted, for instance, looking at exercise, looking at the smoke, looking at different types of surgical intervention, looking at other types of mental wellbeing, sort of interventions. And people have seen is that over time periods, even as short as three months, you can observe epigenetic changes or shifts. As you mentioned, there are, epigenetics is essentially providing that adaptation to environment and lifestyle to an extent. And it’s also can be thought of as cellular memory. So providing some sort of insight about where what your body has been through up to a given point. And that’s why it’s possible to look so accurately at, for instance, biological age, in addition, looking at smoke exposure and as you rightly say, there are some instances where it’s not possible to reverse all of the epigenetic signatures of a factor that has happened, but it is possible to reverse a large proportion of it. So to get one example, somebody who has a high smell smoke exposure school who then for instance, who was a smoker, who then quit, we’d see that score reverse, but there’d be unlikely to ever see it get back to the starting point to zero is if they’d never had any exposure at all. But the extent of this reversibility versus not really depends on the indicator you’re looking at and also the magnitude of the intervention that somebody is undertaking as well.

Richard Jacobs: Do you have any anecdotal evidence, you know, personally for yourself? Yeah, I’m sure you’ve looked at your epigenetics. Have you done any self-experimentation to see if you can change your expression and over what time period? Or do you have a cohort or a group of people that you know, that are using the program and really active in it and try to do things and change it?

Tom Stubbs: Yeah, definitely. So, I mean I don’t really, we’ve got a number of customers who were smokers and then having taken the test, they had been quit having finally for the first time being able to actually see the impact of the habit was having on their health today. And those people are now coming up to the second test in the very near future and we’re excited to see how quitting smoking has impacted that smoke exposure school on a more personal level. I have now taken two epigenetic tests and have made a certain lifestyle intervention in the intervening period and having been seen, in the case of, for instance, biological age, a concomitant reduction in my biological age score, which has been pretty exciting. And we’re looking forward now to starting more and more of these projects, these collaborations and also engaging more customers in a behavioral change to improve their health through epigenetics.

Richard Jacobs: Oh, okay. So you can look and see if someone’s been exposed to smoke. What other things can you show them? What are some of the things that people can find out about themselves?

Tom Stubbs: Yeah, so one, I guess another interesting thing that we’ve, come across is in relation to athletes. So there are a number of athletes, well we have a number of different athletes within Chronomics as customers and when you break those athletes down, what you see is that when it comes to endurance athletes, these athletes have typically very low metabolic state score. So your metabolic state score as measured through epigenetics is looking at really your overall metabolic risks. Combining things like diet, nutrition, exercise, metabolic rates, and genetic predispositions. To give you a measure of how your metabolism is playing out at the epigenetic level. And what you see is that these endurance athletes have a very low metabolic risk. And in contrast, you have a number of athletes that we fall into potentially being classed as classically obese, who actually, although they have an elevated metabolic score relative to endurance athletes actually still appear healthy epigenetically, which is really exciting for us because it’s showing that even though it is true that they are still at elevated metabolic risk relative to these endurance athletes, they are far from being obese in the classical sense. In addition, one, one surprising finding or maybe not surprising, but it was to me anyway, was that these endurance athletes are incredibly healthy, incredibly well trained and have properly optimized diets for the exercise and the sports that they’re undertaking. Tend to also have accelerated epigenetic aging. We don’t fully understand why at this moment in time, but one hypothesis is that this is likely due to the extent of the training regimens that they’re conducting on themselves in order to the functioning and performing at that level. So that’s just another taste of, I have an example where we’ve been looking at specific epigenetic profiles and seeing seen some interesting insights.

Richard Jacobs: What does that mean you’re aging epigenetically? What kind of factors changed to show you that, you know, someones aging prematurely or aging actively?

Tom Stubbs: Yeah, so, as we were mentioning at the start, so epigenetics can be used and is used as the gold standard for biological age measurement that we have today. So listeners may be familiar with telomere length measurements and things of that nature, which look at the ends of your DNA. In the case of epigenetics, relative telomere length measurements, these measurements are much more accurate. And in addition to that, they’re measuring a whole range of molecular functions that are occurring throughout your genome. Telomere length measurements really can’t get up and as we said at the start, Chronomics we’re looking specifically at DNA methylation and this modification and the changes in this modification that occur over time are incredibly informative, not just chronological age, how old you are, biological age, how healthy you are on the inside. And so we’re using measures like this to give people an insight into the risk for atrial diseases. And as mentioned with, some of the people in London suffering from high levels of stress what they can do in order to reduce those factors that are affecting their biological age and improve their health over time.

Richard Jacobs: Awesome. What are some of the pros? Is there anything new in terms of prescriptions? No, not literal prescriptions, but you know, sleep better, get exercise, eat better, etc. I mean, again, you’re in front of data that very few people in the world can see. So what kind of trends or interesting things of modulators of people’s epigenetic status have you seen to be effective?

Tom Stubbs: Yeah. So I guess there’s a couple of things here. The first is that when it comes to what people should do in their everyday life in order to live healthier, I know from my experience is often quite intimidating. The range of things that you can take up in order to live a healthier life. I mean, you’ve mentioned some that there’s a whole host of others, often some that may or may not conflict with each other in terms of recommendations. And to me where epigenetics, genomics and the whole field in general really excels is that it enables you at a personal level to see what things are going to move the needle most for you. So you don’t have to worry about changing all of these various possibilities. You can focus on the thing that’s most informative for your health today. In addition to that, as you mentioned, there’s a whole range of different interventions that are possible. Some, as you mentioned driven by things such as, working on sleep, working on an exercise, working on a diet and with these large data sets, you can also drill down deeper than that, to specific constituents or components of those different areas that you’re mentioning. And you can also then see within the data the difference, gene sets if you like that, that are affected by those different changes that you’re looking to make. So it’s really an exciting time because we’ve never had such levels of information about you and your health.

Richard Jacobs: Yeah. I’ve been interested forever since I learned about epigenetics. What can meditation do on a very, very short term? If I was able to look at you at the genetics. Yeah. Take your blood and then have you meditate for 30 minutes, let’s say, and then draw your blood again. What differences would I see epigenetically? I don’t know if you’ve ever tried to conduct tests like that or you know, do that before and after exercise or before and after, you know, taking a really strenuous test or you know, I mean in the very, very short term, I would think it might be interesting for you to try to characterize if there are any super short term epigenetic changes, you know, within minutes, within hours.

Tom Stubbs: Yeah, definitely. So I guess just a bit on my background. So I, prior to founding Chronomics, worked in research at the University of Cambridge on defining new mechanisms and methods for assessing epigenetics from a vet lab perspective and also from a computational perspective and which is where this Chronomics was then born from looking at how epigenetic predictors of lifestyle factors on aging can be informative for personalized and proactive health management and just to go back to what you were saying about epigenetic changes and how quickly they can occur. So lots of the work I did when I was in the lab, we’re looking at a shorter-term change to cells in a dish. And these could be stem cells, which if you change the media, so the liquid, if you liked that the cells were grown in, you could affect epigenetic marks in the space of minutes to hours and what we know is that for instance, when people make what are called induced pluripotent stem cells, so embryonic likes sales from adult tissues, for instance, skin, you can see huge epigenetic changes in the space of tens of days. And even shorter. And in those settings, you can radically alter measures that we look at. For instance, epigenetic age in a matter of days, you can go from an adult skin cell, but or skin cells or saliva that had an epigenetic age of 70 let’s say 70 years old and reprogram them so that they have an age of zero or even less than zero in intensive days. When it comes to, these are obviously cells in additional not humans and the human body’s made up of trillions of cells. But the fact still holds that it is possible to see epigenetic changes within cells over very short periods of time due to a range of factors and as you correctly say, you could look at, for instance, exercise or you could look at meditation and look for specific changes or specific promoters and things of that nature to understand within specific cell types, how is the epigenome changing in response to these things. And there are a number of publications and number of scientists working on those aspects. And it’s super interesting. The short term changes that can then start to manifest as longer-term changes if done, on a rigorous basis, let’s say, at Chronomics what we look at. So as I said, we look at saliva, we use saliva as our proxy for understanding epigenetics. And we are really interested in understanding long-term changes from this peripheral sampling source that can give us insight into how different environment and lifestyle factors they could be: Internal factors, as you said, linked to mental health that could be manifesting and epigenetic changes in saliva and also external factors. So it could be due to pollution, could be due to alcohol for instance, and how these things are also affecting RPG know and what we can understand in order to live healthier from that information.

Richard Jacobs: Well, do you have any specifics that you’ve seen? From the work that you do, in the data that you’re looking at, is there any personal projects that you’re working on, any changes that you want to make specifically to yourself and have you done little science experiments on yourself or you know, in looking at data have you seen any macro trends in people that, that aren’t obvious that people that don’t collect this data?

Tom Stubbs: Yeah. Okay. So just, I guess another interesting thing that we have seen, which again goes back to, in this case to the biological age model. But we can also look at similar processes or similar insights for the other indicators that we look at. And if we take biological age as an example, what you see when you look at biological age and you look at the specific positions on epigenetic marks. So these DNA methylation marks on your DNA that are informative for biological age from an epigenetic perspective. Well, there’s a couple of things actually. The first is the epigenetic changes with age happen both ways. So there are some positions or epigenetic marks on DNA that gain methylation with age. And there are others that lose methylation with age. Whereas I guess many people think that with age only one or the other would happen. And actually, what you see is both happen. So I suppose the first thing, and then the second thing is that actually if you look at the types of genes near these epigenetic marks that are affected by the aging process, they tend to be in genes that are associated with development. And that for lots of people is quite counterintuitive because it’s kind of, how can genes or epigenetic marks neighboring developmentally related genes. So they’re important for enabling us to grow. How are they then the ones that are most enriched for things that are changing epigenetically with age? And there’s a number of active hypotheses now for why this could be happening and one hypothesis of the balance is due to the playout trippy of these genes. So the fact that yes, these genes function one way during development, but actually once you’re fully formed, they could tell they could then be malfunctioning if you’d like. So not necessarily, yeah, not functioning in an aberrant manner as we age. Even though those jeans were initially controlled and useful during development. So I think one thing that’s exciting is that now that we have this level of detail, you can actually start to dive down and understand mechanisms of processes such as aging, such as metabolism as we age as well, and how, for instance, things such as obesity and the changes epigenetically, how those things are putting us at risk for diseases such as type two diabetes and Metabolic Syndrome as we progress through life. The second category kind of under that, when you look at age-related gene categories, if you like, then genes associated with metabolism which is also interesting in the sense that how is it that biological age is so tightly coupled to your metabolic processes? And again, we don’t fully understand this, but one thing that is really interesting is that when you look at stem cells, so cells that can go on to become different things. And particularly when you look at embryonic stem cells, cells can really become almost any tissue or cell type that they wish. They have very different metabolism too, for instance, differentiated cells. And so perhaps another aspect of this aging process is this shift potentially either two or more, more stem-like a phenotype or well manifestation or a more differentiated one. And the answer is we truly, we don’t understand yet fully how these different gene sets are linked to aging and what function they’re playing in the process.

Richard Jacobs: Have you ever been any longitudinal study of a person epigenetically on how they have changed over the years? Even an animal looked at, you know, as an age, maybe a rat that only lives a few years, you know, epigenetically what its profile looks like. There’ll be a solid cohort of, you know, a thousand rats and profile them every month epigenetically, you know, how are they moving through life and, you know, what do they seem to experience? Is there any common epigenetic set of changes that happens to them?

Tom Stubbs: Yeah. Great. Great question. So yes, there have been epigenetic longitudinal studies done in humans and also in mice and other organisms as well. In the case of humans, as I mentioned, that being epigenetic intervention studies, looking at, for instance, exercise, smoking, and certain surgical treatments as well. If we take mice just to mix it up a bit, I guess, In the case of mice as you say, they live a lot shorter. What’s exciting is that even though they live for a far shorter period of time, it’s actually still possible to predict biological age using epigenetics in these animals. So if you look at a mouse that can typically live three to four years. We and others have shown that you can predict epigenetic age for amounts within a couple of weeks. So the percentage error in the age prediction in mouse is actually equivalent to that found in human. And what’s interesting is as you say, for instance, if you take a mouse system, one, you can get genetically identical strains. So you can study the aging process in the absence of genetic variation, which is useful for looking at things that are happening longitudinally in decent sample sizes without having that additional confounder of genetic differences and so there’ve been a number of interventions that have been looked at mice over the years looking at epigenetics. Some of which are unknown interventions that increase lifespan significantly. So one for instances, caloric restriction. So this is where you reduce the number of calories in a given day for a human or for instance, a mouse has and this caloric restriction is known to have, benefits for lifespan and also health span with it. And in the case of mice, this can be for significantly longer proportions of the overall lifespan. Having not been on calorie restriction, less certainty is around that situation in humans because the studies haven’t been, obviously, have different parameters. They have to be voluntary. They haven’t been followed up for significantly long periods of time yet. But they are being conducted. And what you find is that if you take mice and you have some that are calorically restricted, others that aren’t and you let them get to kind of eight weeks old, 20 weeks old, etc. And what you see is that actually my second were I’ve been under a regimen of calorie restriction look far younger epigenetically then their counterpart mice that have been allowed to eat as much in as often as they like. And this is one type of intervention. You see this for many different types of intervention as well. And to me, what’s really exciting about these findings, in the mouse, I’m actually then extrapolating to the human situation, in a mouse, when we’re talking about calorie restriction, you can already see which mice are going to live longer at the age of eight to 10 weeks and put into human years. That’s kind of by the time they’re 20, 25, you can start to see, okay, under caloric restriction, these mice are epigenetically younger than these mice and they’re going to go to live to older age and be healthier during that period. And where that gets interesting is that then when we put that into a human context, when we’re looking at longevity and we’re looking at ways to try and extend lifespan, it’s obviously incredibly expensive and inefficient to instigate intervention. And also incredibly irresponsible to instigate intervention not knowing for the next 50, 60 years what effect that’s going to have and for then to wait until people stop to die in the different groups to understand whether that intervention was beneficial or not and where epigenetics can come in It can provide that biomarker of the trajectory that things are heading down far earlier than you could do traditionally by waiting until disease outcomes or death following these human studies. And so we’re really excited about the potential for epigenetics, not just for biological age, but also for these other epigenetic indicators, some of which I’ve mentioned today, to really give people insight into and to give us as populations, as researchers, as scientists, insight into how to ensure, people age healthfully and I’m really excited to see where the future takes the field of longevity and with it health spans for humans.

Richard Jacobs: Okay. Very Good. Do you have any programs or level for people to sign up for Chronomics to, you know, to evaluate themselves and how often and to what detail?

Tom Stubbs: Yeah, absolutely. So as part of the future tech podcasts, we are giving a onetime discount to listeners so that they can experience getting the epigenome sequence. In terms of our current customers, most of them do yearly epigenetic testing. We also have some that do quarterly and six-monthly, but we typically recommend yearly testing. And I will share that code with you, Richard, at the end of the podcast and you can send it out with the podcast.

Richard Jacobs: Yeah. And I know you’re probably not able to provide advice, but what are you able to share with people? Well, so they get their genetics done. They think, oh, I’m doomed or so far I’m okay. Or you know, what can they do again, they change their lot in life. Is it a lot going to be changed again with somebody gets their test? What do you do with them then?

Tom Stubbs: Yeah. So I think the first thing to say here is that there are no bad results. You know, epigenetics is just a measure of where you’re at today. And as I said, it’s dynamic. It’s actionable. It’s not like genetics that fixed from birth and you can’t do anything about inherently, it’s modifiable and you’re in control of how it plays out. In terms of advice so we don’t specifically give advice, as a company ourselves. But what we do is we provide every single customer with their own health team, which consists of doctors, nutritionists, health coaches and epigenetic scientists for them to be able to dive into the science more for them to be able to make changes with the security of knowing that a doctor agrees with the changes that they’re going to be making to their lifestyle, independent of what chronic illnesses or diseases or conditions they may be suffering from and also health coaches to help them make those next steps. And same for the nutritionist. So you definitely don’t just get your results and get left there. You get your results and you get the support that you need in order to turn the unseen actionable steps to improve your health.

Richard Jacobs: Okay. Very good. Well, Tom, thanks for coming on the podcast and again in the show notes, we’re going to put the code for listeners, so I appreciate you being here.

Tom Stubbs: Also, thank you again for having me, Richard, and a great to meet everyone and please get involved with epigenetic testing and would also love to hear from anyone if they have any other questions as well. Okay.

Richard Jacobs: All right, great.