Speaker 1 00:00
Kay,

Dr. Kay Durairaj 00:15
well, hello, hello, guys. You're listening to beauty bites with Dr Kay, secrets of a plastic surgeon, and today's podcast is so interesting. We are going to talk all about epigenetics, and this is so exciting, because we'll be able to see molecular change in DNA structure that predicts if your chronologic age and biologic age are lining up if you're getting older or younger from different interventions, we are interviewing Cristiana vanilla, who is harnessing the power of epigenomics for this really precise diagnostics. Cristiana is CSO chief scientific officer and co founder of Mitra bio. And this is a colsa Ventures backed startup. And this is really interesting, non invasive skin testing. And we're looking at data modeling epigenetics, which shows how your skin is aging

Dr. Kay Durairaj 01:05
from different interventions, different topicals. It's such exciting technology. Cristiana graduated from Oxford and Princeton University, where she studied biochemistry and public health economics, and she specialized in molecular diagnostic development. She has her PhD from Queen Mary University of London, all about developing self sampling, epigenetics, based testing for early cancer detection. And that test that she had developed performed well in clinical trials and has recently been implemented by the NHS cervical screening program. So that's wonderful. Congratulations. Cristiana has been named Forbes 30, under 30, for Europe, science and healthcare in 2023, welcome to the podcast. Thank you. Good to be here. Yeah. So I'm so super excited. Can you talk a little bit about like for the lay audience? What is epigenetics, the study of and how does it influence our behaviors, or vice versa?

Cristiana Banila 02:03
Yeah, absolutely. I think I will start comparing a little bit genetics to epigenetics in so in very simple terms, if we can think about it, genetics, the DNA is essentially the cold or the hardware, and then epigenetics is the operating system to the hardware, the software that gives information on how to act, how to move, and so on. Epigenetics are essentially chemical modifications on the surface of the DNA that influence how genes are being expressed down the line. These are affected with aging, with lifestyle, with what we're applying on our faces. So anything when it comes to the to interventions, and they're very, very powerful tool to actually measure change in general, in terms of how the intervention is, is performing on, is performing in general, and then what is, and then it gives information about the biological age of of the system as well, which is very different from the chronological age. Interesting.

Speaker 1 03:16
So why is skin epigenetics so powerfully important to understand how we are aging, and what kind of interventions can we do?

Speaker 2 03:26
Yeah, essentially, epigenetic changes. That is so epigenetic, specifically, DNA methylation, the biomarker that we're investigating, it changes and can be reversed. It can be reversed with intervention. It can be reversed with lifestyle changes and so on. So it is a very powerful marker for us to track if what we're doing is actually improving the state of the organ or is actually making it making it a little bit worse. It's a very good mac, accurate biomarker that essentially is responsive, and that's why it's very powerful.

Speaker 1 04:09
So I've heard people in the audience to understand we have intrinsic factors that influence our DNA, and then we have extrinsic so for example, extrinsic, what hits us would be ultraviolet chemicals in the environment, you know, blue light from our computer screens, toxins and microplastics that are around us or in us, and then internally, you have the reactive stresses of the body, like oxidation, damage from from when we eat excessively, or from, you know, various chemical reactions in the body. And when we're looking at epigenetic testing, we're looking at kind of both of those stressors and how that they influence our DNA changes right,

Speaker 2 04:52
directly, correctly. So when we age, of course, there is a genetic component to it, but most of the aging. In markers, or the way we're aging is influenced by the environment and by the environment, exactly as you mentioned, we're speaking now about what we're exposing ourselves to, so physically outside, but also what we're ingesting, what we're putting in our body. And through epigenetic there are epigenetic changes that essentially control all our organs, all the all the cells in our body, and they are changing with these interventions or with these lifestyle choices that that we're taking. So essentially, if we're managing to monitor that capture the epigenetic information, we can see where we are, how we are in terms of biological aging. Biological age is more of a term, is how our how our body is actually interacting with the environment, the stressors that we're being exposed to, compared to just chronological age, which is just a number for us. And then we can monitor the biological age change with these interventions, with what we're exposing ourselves to to make sure that we're mostly on the right track and we're not aging at the fast pace. Interesting.

Speaker 1 06:12
So in the past, when people look at DNA methylation studies, would it involve blood work, tissue biopsies? Kind of invasive methodologies?

Speaker 2 06:21
Correct, correct. Actually, the the field of epigenetics. Well, epigenetic clocks have has been born around 1213, years ago, and mostly, mostly involve development of of these. So epigenetic crops are essentially just ml models from from blood samples, because they were available for the scientists to be to be able to build these models, and not really you need quite a lot of data to be able to predict very accurately these types of changes we're speaking about. So when it comes to DNA methylation, we're speaking about 26 million CPG, or sites in which DNA methylation can occur throughout the genome. And you need quite a large amount of samples to be able to have good, accurate predictions down the line. And this is the reason why, when the field started, it was a lot of work that that was done using blood, blood samples. But unfortunately, these these tools that have been built in blood that can't are very good at predicting systemic changes, so what happens to the full body in general, as a whole, but are not that great at predicting what happens with a specific individual organ. Yeah.

Speaker 1 07:46
So there are a lot of biologic clocks out there. If people are longevity biohackers, perhaps they're doing some of these biologic age tests like I've heard of. I've heard of so many, but the Horvath test, the grim age test, there are quite a few that are out there. Do you have any ones that are favorites, or you think they're the most accurate relative to the testing that you guys are doing to looking at

Speaker 2 08:13
I'm always I'm always biased, and I always say that my my favorite, is ours, but it really depends. It depends because ours is is organ specific, so it really targets the skin and gives very accurate predictions to the skin. But of course, I'm, I'm a very big fan of Steve Horvath, his he's the pioneer of the field. He's been the one who's the who started all the work on when I put genetic clocks and this type of modeling and understanding what we can do at the end of the day with these types of predictions. So if I would pick a favorite, definitely is going to be it's going to be him, and the work is done.

Speaker 1 08:54
And yet, there's so much controversy about biologic clocks that are already the pre existing ones out there, that people say that they're inaccurate, that you can test the same individual, you know, one hour apart, and get two different test results. So I think challenging, and they're very expensive tests too, and then how specific and sensitive are they? Yeah, it's

Speaker 2 09:16
very it's very true. It's a it's a real problem, and the problem comes more from the technical platform that has been used to be able to do this testing. In the past, most of the work has been done on what, what is called arrays. Erase the array technology, which measures, if I can put it in very simple terms, is essentially a chip with various probes, and then light intensity is measured on the surface of the of those specific chips. And then you have a degree of accuracy, and they're very sensitive to even how the samples are being loaded on the on the platform. Reason why you get such large variability? Why I say I. I'm a big fan of the work that we're doing at Mitra. It's not just because we're doing the work, but because we're doing it in a very smart way. We've actually managed to to build a very good database on sequencing data, only meaning that we have very high depth of every single read associated in, sorry, of every single location in the genome that we're interested in analyzing, and then it is so much more stable, and we get such a large reproducibility in terms of in terms of the sample quality that that we're getting, it's actually more than 96% of the samples that that we're collecting give us very highly, highly qualitative data for us to be able to use in in our modeling down the line.

Speaker 1 10:49
So interesting. How can an individual benefit from knowing, you know, I have my chronologic age, my birth date relative to what my biologic age is? How does, how does knowledge of that empower the individual?

Speaker 2 11:05
Very good question. Well, at the end of the day, the years that we spent on this planet are fixed, right? But then how what we do in this time, it's also very much dependent on us. So knowing the biological age is a very powerful tool for us to know whether we are treating ourselves in the right way in terms of aging correctly, we can age at a higher pace, or we can age at the lower pace. Ideally, we'd like to not age quicker than our chronological age, right? Because we'd like to live as much as we can and then be also healthy in this period of time. So ideally having a lower a lower pace of aging. So knowing the biological age at the end of the day is very important, and it's also associated with health span. Interesting.

Speaker 1 12:00
You guys have a very interesting study on your website where you looked at a skin care product and measured the DNA methylation tapes from before and after, using kind of a pro retinal type of a product. And I found that super fascinating, because you were able to show that the skin that was sun damaged was very highly methylated. And actually, after a month of using this product, you could see changes in the methylation patterns of the tapes, which suggests that the DNA damage. And, you know, methylation patterns get better and improve just from a topical therapy. So yes, we've had, we've

Speaker 2 12:41
had, we've had many studies. The one that that you mentioned about the impact of UV on the skin, we were really interested, interested in environmental exposure. So we've done, we've done the study looking at the same individuals like sun exposed and sun protected. How does the epigenetic profile change and indeed, the sun protected area is aging at the highest so Sun protected area is aging at the lower pace than the sun exposed area on the face, for instance. And the average, the average difference in terms of age is around 3.8 years. And then that was just our curiosity. We wanted to to uncover it. But then we've also done quite a lot of work in terms of understanding intervention impact on the skin, and again, what's what's on our website about retinoid news, that is a little bit of a controversial finding, because we found that short term retinoid use accelerates biological biological aging on the skin. This doesn't mean it is not good for the skin, but it means that in the short period of time, so two months of use that we've tested it, it increases some inflammatory pathways, and we've proved this by doing cell type deconvolution, showing an increase in monocytes, macrophages, granulocytes within within the skin, in the individuals that were using tretinoin. So short term tretinoin use is increasing inflammation, probably shifting the ratio between proliferation and differentiations within the epidermal cells, and we were really interested in following up this study with more longitudinal data points to see what's happening after longer times.

Speaker 1 14:33
Yeah, it's so interesting. I think when we have the theory too and the esthetic side, some of us think that we can't exhaust our fibroblasts, because fibroblast exhaustion comes from repeat simulation, day by day by day. Too much Retin A too much laser, too much micro needling, like never giving the skin chance to rest and heal and like a little bit of senescence, is essential to weed out bad cells and to make sure that good cells have opportunity. Repair. So it's kind of a different way of thinking about skin aging, versus blast your skin every day with products. So has that? Did that preliminary evidence change here? Skin care routine at home? Are you using Retin A at home?

Speaker 2 15:17
I'll be honest with you, I'm not using Retin A right now, after seeing, after seeing those results again, I'm not, I'm not saying retinol red. So red retinol based products are are harmful for the skin. This is my, my own choice to do this. And of course, we would need to do a little bit more longitudinal studies to understand a little bit more what's what's going on within the skin, but there are some interesting theories out there when it comes to cellular exhaustions that we would have to also test out.

Speaker 1 15:54
Yeah, definitely. And then what can you be more specific about what exact genes that you're testing in terms of like skin changes? Are we looking at collagen producing genes last and producing

Speaker 2 16:09
so we're actually investigating a wide variety of genes and pathways that are associated with skin health. The ones that you've mentioned are definitely included and in the panel that we're using right now, we're working with quite an extensive panel covering a lot of the sites on promoter and enhancer regions within the genome. So these are more the regulatory elements when it comes to gene expression, and they influence gene expression quite, quite a lot. And yes, we were looking at, well, pathways and genes that are are very extensive in in skin health, in general, I wouldn't, I wouldn't be able to, like, just go, I wouldn't be able to just, like, pinpoint them, because we're covering, I would say, most of them. And then it matters. Whenever we're looking at the comparative in comparison treated before or after the intervention, that's where it becomes more interesting, because we can, we can see exactly what types of pathways have been activated, what types of pathways have been more enhanced with the treatment or the specific intervention that that has been applied. Interesting.

Speaker 1 17:25
So what type of validation or clinical data, trials, data, do you have that we can kind of talk over?

Speaker 2 17:34
Yeah, we've been we've been doing, we've been being with, we've been very careful and accumulating a lot of validation data. We started off by testing reproducibility of our essay. So essentially, tape stripping, how much, how good, how high quality is the data that we're collecting for us to be able to have good results down the line, and this comes into a point of variability as well. We want to have as little variability from from from subjects as possible. We actually have a paper coming up in NPG aging covering exactly that those those points on reproducibility variability, and also comparing the performance of the clock that we've developed with commonly used clocks, or commonly known clocks, like the one of hovers, which is going to be quite exciting. And then another validation type that we've done, we've correlated, we've performed some correlation analysis with data that was extracted from biopsies. So essentially, we looked at the epidermis area within within the biopsy, versus the cells that we're collecting with tape stripping, and how and the degree of correlation between these types of between the types of biomarkers we could extract from the two sample types. And then we've done quite a lot of work on response for to intervention. Whenever we're organizing clinical trials, we make sure that we have either untreated or a very good control for us to be able to refer back whenever we're doing our assessments and our differential methylation analysis.

Speaker 1 19:22
So interesting. Talk a little bit more about the tape strip process itself, so so the audience can visualize exactly what we're doing with the skin.

Speaker 2 19:32
Sure, it's very, very easy. It's essentially an adhesive that is placed on on the skin. Unfortunately, I don't have it with me here, but as easy as you can imagine, right, putting a piece of adhesive on your face, and then you peel it off, you place it in a container, very similar to an eye cream product. I'm sure you you've used an eye cream product. So you know how these look like. And then there is a stabilizing. Liquid that is poured over the lip gets closed, and then that sample will stay in there, very stable for up to three months at room temperature. And then it can live in the in the fringe for forever, longer. Wow.

Speaker 1 20:17
And it's just one strip, not sequential tapes that are put on and removed.

Speaker 2 20:21
No, no there. So it's not, not just one in one strip. This is just the example. It's actually eight strips that are being placed on the skin, one

Speaker 1 20:29
rather, yeah, directly in the same spot. And then we're putting all eight shape strips go into little jars, or just one

Speaker 2 20:37
Correct, correct. So eight strips on the same spot, they go into the jar with a stabilizing liquid, and that is the sample. The sample gets transported to our laboratories. We take care of it over there. We're performing the DNA extraction, the library preparation for sequencing. We're taking care of the sequencing data, receiving the sequencing data within our facilities, and we do all the work over there.

Speaker 1 21:04
Very interesting. And how deep does the tape strip go? After all that stripping,

Speaker 2 21:09
it goes five to 10 micrometers within the skin. It mostly covers stratum corneum to stratum granulosum layers of the skin. But the actual information that that we're collecting is actually being placed deeper down within the tissue and stratum basale, where the DNA methyl transferase and Tet enzymes are active, and as the cell differentiates up, so it's the epidermal cells goes through our terminal differentiation, the DNA methylation metabolism gets shut down because you don't really need as much gene expression with differentiating cells. And then the DNA methylation that is placed deeper down within the tissue, if you want it travels up to the skin surface as a tattoo, and that's where we capture it.

Speaker 1 22:01
Oh, interesting. So you think also that deeper dermal interventions or systemic interventions can also be reflected on the tape strips.

Speaker 2 22:11
Yes, absolutely, we're actually doing right now quite, quite an interesting study with dermal injections specific serums that are being applied after as well. And then we've also performed a study looking into diet, so how diet influences DNA methylation on the skin and then biological age subsequently. And we found quite, quite interesting, interesting results in terms of, well, the vegan diet, of course, requiring a little bit more vitamins, a little bit more help to

Speaker 3 22:47
be to to actually age at the better pace. Interesting.

Speaker 1 22:54
So are you able to tell us, this audience, what we should be eating and methylation changes?

Speaker 2 23:00
I'm not, I'm not in a position to to give advice right now. But essentially, with, with the vegan diet, of course, there is some deprivation of vitamins. So of course, whenever anyone chooses to go on a vegan diet, so vegan, not vegetarian. Vegetarian is a little bit more more balanced. But with, with a vegan diet, of course, supplementation and making sure that enough vitamins, enough minerals and so on are being also added to the diet is very important.

Speaker 1 23:31
Yeah, very important. Not enough amino acids, especially some of the essential amino acids that you don't get when you're vegan and vegetarian. What? What What kind of role do you see for this type of testing in future, in the future, like personalized skincare products and prediction, like I could do a tape strip before I see a patient and understand the pool, like the depth of their DNA damage better, to understand how to intervene,

Speaker 2 23:58
exactly, exactly? So we'd like to position this test more as a monitoring and then treatment planning tool down the line. So when a patient comes into the clinic, of course, they come with a specific baseline with a specific impact, or in relationship with the environment, if I may, and then doing a tape stripping and epigenetic age assessment of the skin would allow you, the physician, to understand where to start from. What is the damage, what is the base of aging, of the organ of the of the individual? What is, what is their predisposition, how they will age down the line, how they the skin aging phenotypes are going to change without any interventions being done at that moment. And then you can select the type of interventions that are most appropriate and then consistently monitor the individual to understand. Exactly how they progress with a specific intervention, whether they need any change and so on, and ultimately achieve personalization for for everyone.

Speaker 1 25:12
That's very fascinating. I saw earlier this year. L'Oreal had something called Skin print technology, where they had kind of a similar idea. I don't know how you think your system compares, or is it just you checking many more methylation points than what they're doing. It seems like everything was very premature with their but it looked fancy, and I don't

Speaker 2 25:35
have their some of their products earlier this year at Technology Fair in Paris there, what they're doing is quite interesting. It's the main difference is that they're looking at a very select number and very small number of biomarkers, specifically proteins. And what we're doing, we're essentially looking a little bit deeper at the molecular level on multiple types of multiple biomarkers, DNA, methylation, epigenetic, epigenetic biomarkers. And what we are sharing is a little bit more complex and complete, I would say so, information about biological age, information about various skin phenotypes and predisposition for development of those skin phenotypes and so on. So it's not just a couple of proteins that are being expressed or not. And then what we think might be is there

Speaker 1 26:39
a role for some day, imagining skin cancer checks being done at this level, like really, really early, pre cancers and things like that.

Speaker 2 26:47
Yes, yes. And this is something that is, is currently in development in our company as well. We are, well, we're very interested in bringing on the markets the ability to Well, check the impact of UV damage and how this can be linked to underlying cancer predisposition down the line, and also how to differentiate between normal moles, so benign lesions, and also melanoma or others are the types of skin cancer

Speaker 1 27:25
that's so interesting. And as you're you guys at Metro Byron developing some potential consumer facing tools as well. Is that right?

Speaker 2 27:35
Yes, yes. Yes, we are. We're going to start with skincare. So on more of the esthetic sides with our consumer facing products. Right now we are so the work that we're doing is mostly available in clinical trials to understand the effect of interventions on the skin at the molecular level. But then we would like to take all our knowledge and our education so far and put it into the hands of the consumer as well, and clinicians also to help them better manage interventions and prescribe better treatment courses down the line.

Speaker 1 28:18
We are at a really interesting time, and in terms of biology, molecular biology, molecular diagnostics and longevity interest, there's so much consumer demand for interest in longevity, and I really feel that our conversation is changing from anti aging towards more like science backed longevity, like I'm working With the company called rappalogics, or developing a topical rapamycin. And this product, when you apply reverses, you know, the senescence of some fibroblasts makes the fibroblasts behave more youthfully. And yet, where you're kind of banking that transformation into your skin longevity bank and giving yourself resilience and long term change. You may not see immediate, short term changes. So I'm wondering, like, how do we drive our consumer to understand it's not about so much external beauty right now? It's about science powered longevity change and like DNA level changes that we can actually help to direct in the right direction.

Speaker 2 29:21
I agree. I think it's still an element of education that needs to be placed towards towards the consumer to understand this shift. Also, if this is backed with very good clinical data, and put it in the context of the benefits that they will receive down the line of course, is going to be helpful. I think we are. We are experiencing a bit of a paradigm shift right now from going exactly from the immediate in immediate results that we're seeing with the interventions that are available to the next generation of ingredients and also the next generation tools. That will be available to test those, those new ingredients. So it is all about education and information. Scientific publications as well. We have, we're very committed to publishing the work that we're doing. So I mentioned the MPG aging paper that is coming out. We're having, we also had another paper in the British Journal of Dermatology. We're working with, with with actuary, with Candela, to publish one of the case studies that we've been working with. Them very, very interesting results in terms of how to use laser, what types of populations laser is more effective than others, and so on. So this type of data, sorry, this type of education that will be available to the consumer, I think it's just going to pave the way consistently for the for the next generation, if I can put it like that,

Speaker 1 30:54
yeah, this really is this paradigm shift, and we're going to have to teach the consumer that it's no longer to be nine out of 10 women saw a fresh glow. It's gonna be like nine out of 10 people had, you know, methylation score improvements that showed, you know, DNA resilience and the ability to repair and maintain strong foundation of skin for years. Because that's the game that wins. The game for me, like

Speaker 2 31:19
exactly exactly, just extending the skin spam, extending resilience of the skin to be able to withstand all the environmental factors that we're challenged with at the end of the day. So that that would be the goal, to make sure that we're being able to measure that and then to enhance that and to teach it's very good,

Speaker 1 31:43
because people must understand it. And like, I love that you're a boss, girl, woman in science. And like I am too, and we're seeing we're both on different ends of it. But I'm very consumer facing, so I really want to make sure to get the messaging to teach people like this is the new standard of what I'm gonna ask my skincare and my interventions, you know, I really want to see like, high level change and like, we're, we're gonna really anti age if we improve ventilation,

Speaker 2 32:12
maybe, maybe anti aging as well. Is not, is not the best term. I think it's more rejuvenation and resilience that should be promoted a little bit more from resilience

Speaker 1 32:21
is my favorite word for this, because it really implies that your skin can bounce back from any injury, insult, trauma, and have long term maintenance and, you know, foundation that gives you skin support for the decades. That's what, that's what we really need

Speaker 3 32:37
exactly. It's beautiful. Yes,

Speaker 1 32:40
I think it's super fascinating what you're doing. And I applaud you guys. This is huge. I can't wait to do some studies with you and also see some of the results that you have produced there. Where can people find you if they're interested to reach out or learn more?

Speaker 2 32:58
Right now, online, Mitra bio dot tech is our website. There is a portal over there. You can ask any questions. You can reach out for any inquiry. And apart from that, myself and my team are always available on LinkedIn, so you can find us over there.

Speaker 1 33:17
Love it Well, guys, you heard it here first. So we're talking all about the next step and what we need to do to next level, our skin care, our esthetics. It's more than just looking good on the outside, and actually, when we see these external problems, like brown spots, fine lines, wrinkles, it's evidence and senescence that's happening at deeper levels. So I'm so excited to learn more and to be able to someday test skin in the office with these amazing tape strips. That's it for now. Guys, don't forget to find me on my instagram. It's Beauty by Doctor Kay D, R, K, a, y, and our website is the same Beauty by Doctor kay.com that's where you can find our new skin longevity line, which I'm so proud of, which has glutathione, GH, K, copper, NAD boosters and things that improve mitochondrial function. It's all about high level skin care science. That's it for now. Guys, stay beautiful. You Hey.