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Protecting the Mighty Mitochondria · The Science of Skin

• 0:00
  SPEAKER_00: This episode is brought to you by Skin Suiticals, the number one medical aesthetic skincare brand worldwide, and the leader in antioxidant science.
• 0:08
  SPEAKER_00: To learn more, visit www.skinseuticals.com.
• 0:22
  SPEAKER_01: Hello and welcome to Skincare Confidential, the podcast supporting the Science of Skin Care Summit, an annual educational conference occurring in Austin, Texas, in 2024, November 8th through the 10th.
• 0:35
  SPEAKER_01: I am Dr.
• 0:35
  SPEAKER_01: Ted Lane, your host for today, and it is my great pleasure to introduce and welcome Dr.
• 0:41
  SPEAKER_01: Mark Birch Maechin, a professor in at the Newcastle University Institute of Cellular Medicine.
• 0:48
  SPEAKER_01: He is a professor of molecular dermatology.
• 0:51
  SPEAKER_01: Dr.
• 0:51
  SPEAKER_01: Birch Maechin, thank you very much for joining us.
• 0:54
  SPEAKER_02: Great to be here today.
• 0:56
  SPEAKER_01: Great.
• 0:56
  SPEAKER_01: Is it okay if I call you Mark for the rest of the episode?
• 0:58
  SPEAKER_01: Definitely.
• 0:59
  SPEAKER_01: Absolutely.
• 0:59
  SPEAKER_01: Okay, great.
• 1:00
  SPEAKER_01: Please call me Ted.
• 1:01
  SPEAKER_01: Okay.
• 1:01
  SPEAKER_01: All right.
• 1:01
  SPEAKER_01: So so, Mark, so great to have you.
• 1:05
  SPEAKER_01: Thank you.
• 1:06
  SPEAKER_01: We are really going to focus on.
• 1:08
  SPEAKER_01: You've done a plethora of research, but we're going to focus on your research that revolves around the effect of UV and visible light on mitochondrial DNA.
• 1:18
  SPEAKER_01: Sure.
• 1:19
  SPEAKER_01: Let's start with what is mitochondrial DNA?
• 1:22
  SPEAKER_01: Because I'm not sure that many people really understand what this is.
• 1:28
  SPEAKER_02: Sure.
• 1:28
  SPEAKER_02: And actually, um, when you when you start mentioning mitochondria, if people don't, you know, come across it before, their eyes glaze over, you know, they feel a bit sleepy.
• 1:38
  SPEAKER_02: So I always step back and say actually the mitochondria are the batteries of the cell.
• 1:42
  SPEAKER_02: They're the power packs uh that produce the energy that makes everything go round in the cell.
• 1:48
  SPEAKER_02: Uh and so really um uh if you think about mitochondria as your batteries and whether you want to keep the batteries topped up or stop them running down, then that's a good starting place.
• 1:59
  SPEAKER_01: Okay, great.
• 2:00
  SPEAKER_01: So they're the engines of the cell, the batteries of the cell.
• 2:02
  SPEAKER_01: Yeah.
• 2:03
  SPEAKER_01: So they produce the energy, and the energy for the cell is ATP, right?
• 2:06
  SPEAKER_02: Correct.
• 2:07
  SPEAKER_01: Okay.
• 2:07
  SPEAKER_01: And and therefore they are intimately and inextricably involved in cellular respiration.
• 2:13
  SPEAKER_02: Yes, yes.
• 2:14
  SPEAKER_02: And so and so actually um mitochondria are involved in all energetic processes.
• 2:20
  SPEAKER_02: Um there they actually are found in every cell of the body.
• 2:23
  SPEAKER_02: Um I first started working in neurodegenerative uh disease, so muscle and brain, and now I'm working in skin, but mitochondria are in every cell of the body, and so essentially any tissue that requires energy, ATP, mitochondria at the center of it all.
• 2:39
  SPEAKER_01: Okay, great.
• 2:40
  SPEAKER_01: So so absolutely integral to the cell's functions.
• 2:43
  SPEAKER_01: Yeah.
• 2:44
  SPEAKER_01: And and there's this mitochondrial DNA that you're really focusing on, which is an interesting uh DNA, right?
• 2:51
  SPEAKER_01: Because it's different than than the genetic material that we commonly think about in the nuclei of our cells.
• 2:57
  SPEAKER_01: This one, which which of course is derived from your your both sets of your mother and your father.
• 3:03
  SPEAKER_01: The mitochondrial DNA is different, though, isn't it, Mark?
• 3:05
  SPEAKER_01: Can you go through that with us?
• 3:06
  SPEAKER_02: Yeah, so so the the DNA we get from our mother and father is what we call the nuclear DNA.
• 3:12
  SPEAKER_02: All right, that's much bigger than mitochondrial DNA.
• 3:15
  SPEAKER_02: And mitochondrial DNA by comparison is much smaller, but actually, because of where it is and what it does, and it's at the kind of the the fulcrum of the bioenergetic process, it has a kind of almost like a an overinflated role compared to what its DNA is.
• 3:32
  SPEAKER_02: And so, unlike the nuclear DNA, which we get from a mother and father, the DNA housed inside the batteries of our cells actually is inherited from our mothers.
• 3:42
  SPEAKER_02: So it's maternally inherited only because of various processes, um, where the the mitochondria from the from the father is kind of tagged with a with a kind of like a um a death protein, as it were.
• 3:57
  SPEAKER_02: And so that gets kind of mashed up.
• 3:59
  SPEAKER_02: So actually it's maternally inherited.
• 4:02
  SPEAKER_02: And also the interesting thing about it is the fact that um it's not protected by a lot of proteins uh like histones.
• 4:11
  SPEAKER_02: So essentially it's naked DNA, all right?
• 4:14
  SPEAKER_02: DNA with its clothes off, as it were, if for want of a better word, naked DNA.
• 4:18
  SPEAKER_02: So because of that, it is very vulnerable to damage and stress in the cell, however that stress may present itself.
• 4:27
  SPEAKER_01: Oxidative stress is what we what we're gonna focus on.
• 4:31
  SPEAKER_01: Uh and so just to reiterate, so this is DNA that that is important, integral for the mitochondrial functioning.
• 4:38
  SPEAKER_01: It doesn't have access to the nucleotide repair enzymes, all of the the not all, but many of the enzymes that we commonly attribute repair in our nuclear DNA, the mitochondrial DNA does not have the advantage of of being exposed to, really.
• 4:55
  SPEAKER_02: Correct.
• 4:56
  SPEAKER_02: And so for so for example, um normally, you know, so if you have um damage in your nuclear DNA, which is also, you know, which is protected by these histones and things like that.
• 5:07
  SPEAKER_02: So let's say if it gets through the histones and you get DNA damage in your nuclear DNA, like creating a crime scene, so to speak, um the nuclear DNA is very efficiently repaired.
• 5:19
  SPEAKER_02: So the crime scene is tidied up.
• 5:21
  SPEAKER_02: All right.
• 5:21
  SPEAKER_02: So you can go in and see if a cell has been stressed or under trauma and nuclear DNA, and the the because it's such a good repair mechanism, there are damage, it isn't obviously that we we know that.
• 5:31
  SPEAKER_02: But for the large part, those that damage is repaired.
• 5:34
  SPEAKER_02: In the mitochondria, they are lacking certain repair mechanisms or are inefficient at normal repair mechanisms, and so because of that, you get an accumulation of damage.
• 5:46
  SPEAKER_02: For example, um, there's a a disorder called xeroderma pigmentosum, right?
• 5:52
  SPEAKER_02: Which which in dermatology um is where um people with XP, and in America, I think children with XP are called moon children because they only go out at night, all right?
• 6:03
  SPEAKER_02: Because actually, if they go out during the day, there's they they suffer a potential risk of two to three thousand-fold increase in skin cancer because they can't repair their sun-induced DNA damage, right?
• 6:15
  SPEAKER_02: Right.
• 6:15
  SPEAKER_02: So, what is interesting, so those are XP patients.
• 6:19
  SPEAKER_02: What is interesting is in the mitochondria, they do not have the same repair mechanism, they do not have nucleotide excision repair, and so because of that, the mitochondria can't repair their sun-induced DNA damage either.
• 6:33
  SPEAKER_02: And actually, um that, you know, that because mitochondria and all others, then actually we have kind of almost many examples of XP existing in in our skin of every individual.
• 6:45
  SPEAKER_01: Interesting.
• 6:46
  SPEAKER_01: And so do the mitochondria does the mitochondrial DNA therefore carry these mutations and and could that be a sign of aging?
• 6:55
  SPEAKER_01: Could could you could you effectively determine the aging of the skin based on mitochondrial DNA damage because it's not being repaired?
• 7:04
  SPEAKER_02: Yes, yes.
• 7:04
  SPEAKER_02: And so there's there's there's actually um you know, before I before I answer that question, you know, the your listeners might be thinking, oh my goodness, you know, I I'm I got many examples of XP in my in my skin all the time, or actually in in all your Yes, let's avoid mass hysteria marking.
• 7:20
  SPEAKER_02: Okay, let's avoid mass hysteria now, okay, because basically what happens is um uh there's something called complementation within mitochondrial DNA.
• 7:29
  SPEAKER_02: All right.
• 7:30
  SPEAKER_02: Okay.
• 7:30
  SPEAKER_02: So because um so in your nuclear genes, in your mother and dad, you know, there's two copies, two alleles, all right.
• 7:37
  SPEAKER_02: In mitochondria, you have hundreds and thousands of copies depending on which tissue you have.
• 7:44
  SPEAKER_02: All right.
• 7:44
  SPEAKER_02: So muscle and brain would have thousands, skin would have hundreds, you know, for example.
• 7:49
  SPEAKER_02: And so because of that, what what that means is you have complementation.
• 7:53
  SPEAKER_02: In other words, the the undamaged mitochondria help out the damaged mitochondria.
• 8:00
  SPEAKER_02: And so essentially what happens is you can your cells can tolerate quite a lot of damage in your mitochondria before it begins to affect cellular function, all right, which actually from a from a marker point of view, and we we'll probably come on to that later, is very useful.
• 8:14
  SPEAKER_02: But actually, uh, you know, I just want to, you know, that should stave off mass exterior, all right?
• 8:19
  SPEAKER_02: Because so actually, you know, mitochondria are very good at tolerating its own damage because the the kind of undamaged ones, it's a very it's a very kind of generous thing, isn't it?
• 8:28
  SPEAKER_02: You know, the fact that the ones that are undamaged helps out the ones that are damaged.
• 8:32
  SPEAKER_02: And wouldn't that be wouldn't that be nice across the world in in all societies?
• 8:35
  SPEAKER_02: But you know, so it's very, very, you know, nice from that point of view.
• 8:38
  SPEAKER_02: You alluded to this thing about um about aging.
• 8:42
  SPEAKER_02: Now we know that aging, uh you know, there's many factors to do with aging, and there's telomeres and senescence and all this kind of stuff that goes on there.
• 8:51
  SPEAKER_02: And actually, the reason why mitochondria have begun to take kind of you know quite a major role in aging is because there's um a theory called the the mitochondrial theory of aging, and at the center of that is what's called the vicious cycle.
• 9:07
  SPEAKER_01: Okay.
• 9:07
  SPEAKER_02: And essentially you've got three components to the vicious cycle, one of which is mitochondrial DNA, which we've mentioned.
• 9:14
  SPEAKER_02: The other is the function of the mitochondria, which is the function of the battery, and the third component is the oxidative stress, which you've also mentioned as well.
• 9:24
  SPEAKER_02: And so they exist in a little triangle, all right?
• 9:26
  SPEAKER_02: And so essentially what what it means is the fact that um if mitochondria is sitting there minding their own business, they're they're unprotected, they don't have these histones, um, they have inefficient repair mechanisms, so they accumulate DNA, they accumulate DNA damage, which affects the function of the battery, so that function is compromised, and then because the function is compromised, it's almost like the exhaust um fumes of a of an engine that what happens is they they pump out more reactive option species, which increases oxidative stress, which in itself then damages more mitochondrial DNA, affects mitochondrial function, leads to more exhaust fumes, more oxidative stress.
• 10:10
  SPEAKER_02: And you get this kind of runaway vicious cycle of aging.
• 10:14
  SPEAKER_02: And so the challenge there is to move us from the fast lane of aging to the slow lane of aging by interrupting and slowing that vicious cycle down.
• 10:24
  SPEAKER_01: Okay.
• 10:25
  SPEAKER_01: And is that vicious cycle related to this term inflammaging, where we have the inflammation associated with aging?
• 10:32
  SPEAKER_02: Yeah, so so all of this is related because because actually, you know, put uh you know, part of inflammation process is this increase in oxidative stress, and there's a kind of key trigger aspect to that.
• 10:43
  SPEAKER_02: And the reason why mitochondria are involved in that um and have a if you draw a Venn diagram, there would be an overlap there, is the fact that um uh two things, I mean, that lots of things happen when when we age, all right.
• 10:55
  SPEAKER_02: So I'm simplifying this dramatically, right?
• 10:57
  SPEAKER_02: Of course.
• 10:57
  SPEAKER_02: Mitochondrial-centric point of view.
• 10:59
  SPEAKER_02: Okay, okay, so you know, um, but when you look in the mirror, bit you know, as it were, deeper down, um, two things happening when you age.
• 11:08
  SPEAKER_02: The uh with mitochondria, your batteries tend to run down.
• 11:11
  SPEAKER_02: Okay, and we know that, you know, the the the uh the uh the way we make ATP, the amount of ATP we make declines with age.
• 11:18
  SPEAKER_02: Okay, and what tends to increase is the fact that oxidative stress increases.
• 11:23
  SPEAKER_02: Now, the mitochondria produce 990% of cellular oxidative stress by what's called a cascade system.
• 11:32
  SPEAKER_02: It's like knocking over a domino.
• 11:34
  SPEAKER_02: You knock over one thing and it leads to a cascade.
• 11:36
  SPEAKER_02: And so that's why there's a link with that information.
• 11:41
  SPEAKER_00: This episode is brought to you by Skin Suiticals, the number one medical aesthetic skincare brand worldwide, and the leader in antioxidant science.
• 11:50
  SPEAKER_00: To learn more, visit www.skinseuticals.com.
• 11:57
  SPEAKER_01: Let's focus on the oxidative stress and and how to prevent it or or mitigate it as much as we can.
• 12:04
  SPEAKER_01: You've done some research to show that both UV and visible light affect the mitochondrial DNA, right?
• 12:11
  SPEAKER_02: So we haven't done visible light affecting mitochondrial DNA, but we've done uh UV and uh well, we've actually done visible with infrared.
• 12:21
  SPEAKER_02: Okay, so we haven't been able to tease out the the infrared, but what we did is yeah, we we we uh we kind of divided sunlight or solar light into different components, the UV and then visible light and infrared.
• 12:33
  SPEAKER_01: Yeah.
• 12:33
  SPEAKER_01: Okay.
• 12:34
  SPEAKER_01: And can you tell us the results of this research in terms of obviously we would imagine the UV light affects change, cyclobutine, pyramidine, dimers, CPDs that occur in the mitochondrial DNA, like they occur in the nuclear DNA.
• 12:47
  SPEAKER_01: But what about the visible and infrared light that you've researched?
• 12:50
  SPEAKER_02: So, yeah, so this was a publication that um that was probably about six years ago that we that we published, and we're um still working on on some of the implications of that.
• 13:02
  SPEAKER_02: But it's but very simply what we found, we asked the question.
• 13:06
  SPEAKER_02: Um there's been a lot of reports about the role of UV, and we know UVA, UVB has a profound effect on on cellular damage, and so we use mitochondrial DNA as well as nuclear DNA, and we measured reactive option species as well as markers of that damage, almost like uh parameters of the cell trauma, you know.
• 13:26
  SPEAKER_02: This crime scene that we've been talking about, you know, the fact that mitochondria aren't very good at tidying up the crime scene, so it's still there.
• 13:33
  SPEAKER_02: So we we we um we hit some uh skin cells with um UV, but also what we did is we um using various filters using a solar simulator, so which simulates sunlight.
• 13:47
  SPEAKER_02: We then added back um the visible and the infrared component of uh of sunlight in the study.
• 13:55
  SPEAKER_02: All right.
• 13:55
  SPEAKER_02: So we didn't we couldn't actually separate out the time, um, although we are able to now, visible light and infrared.
• 14:01
  SPEAKER_02: So so you know, and what we found was the fact that um um separately the visible and the infrared really didn't do an awful lot under the conditions that we used.
• 14:14
  SPEAKER_02: Not to say that they don't have an effect, but under the conditions that we used in sunlight, they didn't seem to have much effect on the parameters, the parameters being nuclear DNA damage, mitochondrial DNA damage, and reactive oxygen stress.
• 14:27
  SPEAKER_02: But actually, when you um when you combine it with a with UV, it almost poises, it almost enhances the visible light and infrared um effect, which tells us the fact that on their own they may not have so much of an effect, but actually when the cell is, as it were, damaged or troubled by UV, their activity is enhanced profoundly by, you know, mechanism, the fact that you've actually got some stress happening already, and then when you add some different stress, then it that enhances that.
• 15:00
  SPEAKER_02: And so what we found is um so so there's a difference there, and interestingly, we found that was a difference between the fibroblasts, which are in the dermis, and the keratinocytes and the epidermis.
• 15:13
  SPEAKER_02: What we found is that that actually this enhancing effect was really only observed in the dermal fibroblasts and not in the epidermal keratinocytes, and so it tells us the fact that different layers of the skin will react differently to different wavelengths of light, which you will intuitively feel anyway, because you know penetration, but actually there'll be something different about dermal fibroblasts dealing with these different stresses, and so and so because of that, that has implications in terms of aging, protection, everything else.
• 15:42
  SPEAKER_01: That's fascinating.
• 15:43
  SPEAKER_01: So when you're referring to the different wavelengths, as we know the UVA, the longer wavelength, dives deeper into the skin, it penetrates deeper into the skin, hence probably affecting the fibroblast more than UVB, for example.
• 15:54
  SPEAKER_01: Right.
• 15:55
  SPEAKER_01: Yeah.
• 15:55
  SPEAKER_01: Uh okay, so there's this nefarious synergy that happens with with visible and UV light uh to enhance the production of reaction, reactive oxygen species and and therefore damage.
• 16:07
  SPEAKER_01: Now, did you do in your research, did you include any kind of um protection, uh antioxidant protection, sunscreen protection, anything like that?
• 16:17
  SPEAKER_02: Yeah, so we um so within that study we didn't so so that study um that was published in um it was published in FASEB, um, we didn't actually include any um protection or anything like that.
• 16:30
  SPEAKER_02: It was just a question of what happens when you um traumatize cells in this way.
• 16:35
  SPEAKER_02: And um, you know, the conclusion of that is there'll there'll be different chromophores for infrared, visible, and UV in in in those cells.
• 16:43
  SPEAKER_02: And the the I guess the um aspect in terms of protection is if you find out what those chromophores are, then you can actually design intelligent protection for them.
• 16:55
  SPEAKER_02: Okay.
• 16:56
  SPEAKER_02: And so um, but with the the tools that we have, and then we're actually able to look at um using some protection products to actually see whether or not um they can help to protect against um UV-induced mitochondrial DNA damage because um you know the um uh the the nice system that we have is the fact that you you know we know UV damages um mitochondrial DNA very directly.
• 17:22
  SPEAKER_02: We don't understand the mechanism of infrared invisible, so in terms of you've got to start somewhere, so let's start with UV.
• 17:28
  SPEAKER_02: And that's part of the study that that um uh we've done recently that we're gonna present at the EADV um uh this coming week, actually.
• 17:37
  SPEAKER_01: Ah, wonderful.
• 17:38
  SPEAKER_01: Okay.
• 17:39
  SPEAKER_01: Can you talk about the study or do you want to wait until you present it?
• 17:42
  SPEAKER_02: Um well I think um I think we can I think we can we can talk about because uh obviously it's produced as a as an abstract um at the conference, so it's it's it's obviously um it's probably even um uh public domain now.
• 17:58
  SPEAKER_02: So so so yeah, yeah.
• 17:59
  SPEAKER_02: So um so I think uh we can we can um we can talk about that because it's actually been um um submitted and accepted as a as a poster presentation at the EADV.
• 18:10
  SPEAKER_01: Okay.
• 18:10
  SPEAKER_02: So um so um within the study we haven't actually um we actually worked with um skin suiticals um and the work that was done was completed by our spin-out company called Skin Life Analytics, which is a Newcastle University spin-out company.
• 18:27
  SPEAKER_02: In other words, what happened is is the fact that the uh you know you know it's not similar to most universities, yeah.
• 18:34
  SPEAKER_02: You allow that technology that you have as an academic to be spun into a spin-out company in exchange for you know shares and all that kind of stuff and things like that.
• 18:43
  SPEAKER_02: So it just means the fact that we can actually um uh take a lot of the clever stuff that we do and then actually help to make a difference in in the cosmetic world, etc.
• 18:52
  SPEAKER_01: Commercialise it so it can be used.
• 18:54
  SPEAKER_02: Commercialise it, that's right.
• 18:55
  SPEAKER_02: So it actually puts it put in power puts it into the hand of more people more people, you know.
• 18:59
  SPEAKER_02: Understood.
• 18:59
  SPEAKER_02: You know, which is which is great.
• 19:01
  SPEAKER_02: So so actually the the um the work was that was done was obviously between skin suiticals and um uh skin life analytics.
• 19:10
  SPEAKER_01: Okay.
• 19:11
  SPEAKER_02: And what we did was we asked the question um whether or not um these sun protection products which were at uh SPF 50 um could actually prevent the um UV-induced mitochondrial DNA damage.
• 19:27
  SPEAKER_01: Now, in both keratinocytes and fibroblasts.
• 19:30
  SPEAKER_02: No, we just did it in fibroblasts.
• 19:32
  SPEAKER_02: Um the only reason yeah, the only reason we didn't do keratinocytes is because um with um with keratinocytes, the best model is actually using primary keratinocytes, so you get a lot of donor variability.
• 19:44
  SPEAKER_02: So you have to do it so loads and loads of times, and so it kind of makes the the system a bit noisier.
• 19:50
  SPEAKER_02: So actually, by using um human dermal fibroblasts that you can actually get cell lines which actually make the whole thing you know reproducible and you know what you're gonna get every time.
• 20:00
  SPEAKER_02: So the only change that you see will be due to the intervention, and the intervention at this point is obviously a plus or minus this the sun protection product.
• 20:11
  SPEAKER_01: Okay, and and what we've learned from your research that was published six years ago is that these dermal fibroblasts are are much more sensitive to visible plus UV light than the keratinocyte.
• 20:20
  SPEAKER_01: So it makes sense to focus on the fibroblasts as well from that perspective.
• 20:24
  SPEAKER_02: Absolutely, absolutely.
• 20:25
  SPEAKER_02: So there's a lot of sense in that, and there's a lot of traction with that study.
• 20:28
  SPEAKER_02: And so um because we've done a lot of work on you know doses and everything else, what we did was we took our human dermal fibroblasts and we irradiated them with um effectively two standard erythemal doses.
• 20:42
  SPEAKER_02: And so the difference between standard erythemal dose and minimal erythemal dose is because MEDs are take into consideration skin types, whereas SEDs don't.
• 20:52
  SPEAKER_02: It's a very much a kind of a pure medical physics.
• 20:54
  SPEAKER_02: Uh, and because I've been kind of um brought up by medical physics, they don't allow me to talk about MEDs, so so I have to talk about SEDs.
• 21:03
  SPEAKER_01: Yeah, if I could just interject.
• 21:04
  SPEAKER_01: So a minimal erythema dose is is based on your skin type, right?
• 21:08
  SPEAKER_01: It's the amount of UV that will cause redness in the skin, the erythema is redness, right?
• 21:13
  SPEAKER_01: So everybody has their own MED.
• 21:16
  SPEAKER_01: And what you're saying is that would be very difficult to do in vitro.
• 21:19
  SPEAKER_01: Uh and so in instead you use a standard dose that you know will cause the damage that you're looking for.
• 21:24
  SPEAKER_02: Perfect, yes.
• 21:25
  SPEAKER_02: And that actually two SEDs um is is roughly uh equivalent to about 20 to 40 minutes of exposure in the Mediterranean sun.
• 21:34
  SPEAKER_02: All right.
• 21:34
  SPEAKER_01: Okay.
• 21:35
  SPEAKER_02: So that's so it's a very physiological dose.
• 21:37
  SPEAKER_02: It's not, you know, you're not looking at something which um, you know, is is is hours and hours.
• 21:42
  SPEAKER_01: So i if I can interject, just clinically, twenty to forty minutes outside is pretty much what we tell people to get weekly for vitamin D conversion.
• 21:50
  SPEAKER_01: So this is not outside of the norm of what dermatologists commonly recommend, quite frankly.
• 21:55
  SPEAKER_01: So very interesting.
• 21:56
  SPEAKER_01: Okay, I can't wait to hear the results.
• 22:00
  SPEAKER_02: Actually, within that context, and I've been involved in in many vitamin D discussions, et cetera, because obviously we need exposure to get vitamin D.
• 22:06
  SPEAKER_02: Um, obviously this is clearly in single cell monolayers rather than multi-layer skin.
• 22:11
  SPEAKER_02: And so actually you can get more sun exposure and multi-layer skin without actually being uh again being traumatized by what I'm about to tell you.
• 22:20
  SPEAKER_01: Yeah, good.
• 22:21
  SPEAKER_01: Well, thank God our our fibroblasts are not directly exposed to the sun on any given day.
• 22:25
  SPEAKER_01: So that's clearly.
• 22:26
  SPEAKER_02: Exactly, and there's a reason for that, and there's reason the fact that those fibroblasts are below the stronger coneum, below all these other cells, and so and so because of that, and there's good there's good reason for it.
• 22:35
  SPEAKER_02: And so what we did is we um irradiated um those cells uh and we did our proper positive and negative controls.
• 22:43
  SPEAKER_02: The negative control is obviously covered up and the positive control is fully exposed, and also we included a sham control, which is basically chassis with no SPF.
• 22:54
  SPEAKER_02: All right, so so essentially what we found with those positive and negative controls was the fact that we got our maximum damage on our minimum damage, all right.
• 23:02
  SPEAKER_02: So everything worked from a technical point of view, and then you do the same experiment, uh, and you actually have sun protection products, and there were four of them, um, suspended between the um light source, the UV light source, and the underlying skin cells.
• 23:19
  SPEAKER_02: All right, so if you can imagine a kind of three-way thing, you've got the light source up above, you've got the sun protection products and a solid support, which is UV transparent uh below, and below that you've got the the skin cells.
• 23:33
  SPEAKER_02: And then having irradiated those cells, what you then have to do is you then have to um extract the DNA from those cells, and then um uh assay using our proprietary technology, which has actually taken many years to, you know, we've had to walk around the whole genome and everything else to find out that what what what is what the mitochondrial genome is sun-specific or sun sensitive, right?
• 23:58
  SPEAKER_02: Interesting.
• 23:58
  SPEAKER_02: Okay.
• 23:59
  SPEAKER_02: So we use those um proprietary primers to ask the question do the sun protection products um um lead to decreased damage or not at all, or even increased damage?
• 24:11
  SPEAKER_02: You know, you've got to have every you know three options available to you.
• 24:15
  SPEAKER_02: Right.
• 24:15
  SPEAKER_02: Um and so what we found uh in all four instances was the fact that um the um sun protection product products um allowed a protection in in all cases up to about about 320% uh protection or 3.2 fold protection compared to when it's not there.
• 24:37
  SPEAKER_02: So basically, so they're doing a very good job, and uh and that's really based on the mitochondrial DNA damage.
• 24:45
  SPEAKER_02: And what we do is we do our appropriate controls, we actually have loading controls, we actually allow for um a mitochondrial loading gene as well, which is which is well away from the damaged area.
• 24:56
  SPEAKER_02: So we we we do all our appropriate controls.
• 24:59
  SPEAKER_02: What we did find, because I guess the next question would be okay, Mark, of these four products, is there a is there a is there a winner there?
• 25:06
  SPEAKER_02: Is there a front runner?
• 25:07
  SPEAKER_01: That was my question.
• 25:08
  SPEAKER_02: Yeah, the front runner.
• 25:10
  SPEAKER_02: If I was a vetting man, you know, as a horse race, which is which is the which one do I use, Mark?
• 25:14
  SPEAKER_01: Which one do I use?
• 25:15
  SPEAKER_02: Well, actually, because they're all at SPF 50 and and um containing um you know, because they afford that protection, there were differences between them, but no significant differences between them.
• 25:27
  SPEAKER_02: So all four showed a significant difference between you know maximum sun exposed, uh, you know, and so there were a highly statistical difference.
• 25:35
  SPEAKER_02: I think the the they were all less than uh 0.002, you know, significant.
• 25:40
  SPEAKER_02: So so very highly significant.
• 25:42
  SPEAKER_02: But when you actually assay the uh analyze the differences between the products, even though by eye there are slight differences, statistically, there's no difference at all between between the four.
• 25:54
  SPEAKER_01: Thanks, Mark.
• 25:54
  SPEAKER_01: And can you please go through the the different ingredients that were included in the four sunscreens that were tested in the study?
• 26:00
  SPEAKER_02: Yeah, so the four sunscreens that were tested were um uh top-selling skin suitical sunscreens.
• 26:07
  SPEAKER_02: And um both um mineral and organic uh sunscreens were used in those products.
• 26:15
  SPEAKER_02: And uh it also included a variety of filters, either US or international filters, due to the regulation requirements based on the formula.
• 26:25
  SPEAKER_02: But we know the fact that we only put on about 40 to 60 percent thickness on a good day.
• 26:31
  SPEAKER_01: Right, because we're supposed to put on you know at least an ounce of sunscreen on normal sun-exposed areas.
• 26:37
  SPEAKER_02: So nobody really puts on two milligrams per centimeter squared, which is actually what the SPF is tested at, right?
• 26:44
  SPEAKER_02: Okay, even if you know you're meant to put on two milligrams per centimeter squared, I would challenge anyone to put it on regular.
• 26:50
  SPEAKER_02: And so actually, the idea of actually going for a higher SPF means you probably because of inadequate application, as it were, or patch application, you actually end up with the with the with the protection that you would probably want to have.
• 27:06
  SPEAKER_02: If does that make sense rather than if you go for 30, you end up with less.
• 27:09
  SPEAKER_02: And so actually, you know, going with for 50 is quite prudent from the experimental point of view, because that's probably what you might suggest that that that you might start with.
• 27:20
  SPEAKER_01: Well, I can tell you that that mirrors what dermatologists say every day, uh, which is use the highest SPF you can find because you're probably not putting it on correctly anyway.
• 27:28
  SPEAKER_02: Yeah.
• 27:28
  SPEAKER_02: Yeah, yeah.
• 27:29
  SPEAKER_02: Absolutely.
• 27:30
  SPEAKER_02: And and you know, as I say, we we talk about this a lot, and you know, for within the within the discipline, even though you know what two milligrams centimeter squared looks like, I I I just don't think people would would put that on on a regular basis.
• 27:44
  SPEAKER_02: You might do when you're thinking about it, but not when you're rushing and things like that.
• 27:48
  SPEAKER_01: So as we kind of end our time here and it's gone by so quickly as it always does, um, what are your thoughts now about this?
• 27:54
  SPEAKER_01: You hinted to you you mentioned this a little bit, but it's something that I've thought a lot about and and continue to as we consider the applications of regenerative, the hallmarks of aging to the uh aging science and and inflammatory skin disease as well.
• 28:07
  SPEAKER_01: And and your thoughts on uh kind of turning away from clinical signs and symptoms as endpoints towards more molecular uh endpoints as we look at, you know, as you mentioned, DNA, uh DNA protection instead of an SPF for for uh sunscreen.
• 28:25
  SPEAKER_01: You know, I think we as we look at a lot of the skincare um products that we use, we're we're seeing the skincare industry move away from just using clinical endpoints, you know, clarity, pigmentation, fine lines and wrinkles, and now we're moving towards more you know DNA expression, RNA expression, what are the molecular endpoints, DNA methylation.
• 28:46
  SPEAKER_01: You can you can go on and on.
• 28:48
  SPEAKER_01: Do you think that we're at the age now where we should start seeing that more and more with not only SPF, but also you know, the the more common skincare uh products that are being introduced now?
• 29:01
  SPEAKER_02: Yes, I th I think what it what it does is it it it you know the findings that we've we've you know with the abstract and the poster that we're presenting at the EADV with skin suiticals and skin life analytics, you know, with the with the technology, as it were, spun out from from Newcastle University, there are clearly you know, looking at the literature, there are uh you know very uh good molecular markers that reflect the damage not only caused by UV but pollution, lifestyle, diet, etc.
• 29:30
  SPEAKER_02: And so it's a very much a holistic um aspect.
• 29:33
  SPEAKER_02: And so really, you know, part of the the kind of strapline of the the spin-out we set up was to make the invisible visible.
• 29:40
  SPEAKER_02: And I think that's the question you're asking, isn't it?
• 29:42
  SPEAKER_02: It's almost like you know, these deeper down invisible things that are going on, and and you know, one of our invisible things is mitochondrial DNA damage, but there are other invisible things that are going on as well.
• 29:54
  SPEAKER_02: And so you want to make them visible to us so that we can do something about skin protection, you know, repair, all those kind of things before we see the visible signs that we're all familiar with, you know, those wrinkles, fine lines, uneven skin tone.
• 30:11
  SPEAKER_02: Um, so we want to do something about it as earlier stage than actually once it becomes visible in terms of you know by you know skin imaging, etc.
• 30:20
  SPEAKER_02: And and we you know we use skin imaging machines as well, so it's not like I'm saying they're not good, they are.
• 30:25
  SPEAKER_01: Like control microscopy or exactly, exactly.
• 30:28
  SPEAKER_02: You can you know, um clearly what you can do is you can use these kind of um deeper molecular markers, the invisible things, to actually set see whether or not an intervention works.
• 30:41
  SPEAKER_02: And actually, if you know, with mitochondrial DNA uh and these other markers giving you a actually an uh an objective measure, you can tell whether or not what you're intervening with or your lifestyle is making that damage more or less.
• 30:55
  SPEAKER_02: And so you can manage your lifestyle because you can see whether something's going up and down.
• 31:01
  SPEAKER_02: You know, with nuclear genes, um, you've got it, you have a propensity, you have a risk ratio of getting something, not getting something with things like mitochondrial DNA, because it's so sensitive, it can go up and down depending on the stress to your cell.
• 31:16
  SPEAKER_02: And so, because of that, you've got a way of tracking how your damage is going with your lifestyle, and then working with the interventions that are available, and you know, some protection products clearly are of in a very effective measure, you know, whether or not you're applying it properly, if it's working properly, etc.
• 31:34
  SPEAKER_02: etc.
• 31:34
  SPEAKER_02: So I think it's very exciting what what you could bootstrap the new markers to to things that we're familiar with, like SPF, because that's what we're familiar with, but if we can, it's like we can actually bootstrap it to something else, and then actually we can maybe mature those protection factors to other parameters.
• 31:51
  SPEAKER_01: I mean, if you you can the analogy here to me is this constant glucose monitoring that we use in diabetic patients, for example, right?
• 31:58
  SPEAKER_01: Where they have cons constant feedback on the control of their of their condition.
• 32:05
  SPEAKER_01: The idea if we apply that to skin aging, perhaps it's skin scrapings that we send in once a month or once every year to to a lab such as yours to do the molecular, you know, um analysis of aging.
• 32:20
  SPEAKER_01: And that could tell us, okay, it's time for you to start using this product or change this in your diet or change this in your lifestyle, for example.
• 32:27
  SPEAKER_01: So I think as we you know progress in the science, Mark, I hope you agree with this.
• 32:31
  SPEAKER_01: I think it's time for us to start considering what we do in other diseases or states is something that we could do to aging as well.
• 32:38
  SPEAKER_01: We need to treat it like uh aging to me is a disease that we can treat.
• 32:42
  SPEAKER_02: Yeah, yeah, exactly.
• 32:43
  SPEAKER_02: And actually, we've um within the same spin-out company, you know, within the work we've talked about with the EADV, you know, we've it's like a contract research lab, you know, it's like we're there to test products and and and actually um, but also what we've got is this skin scraping that you've talked about, we can actually take a skin swab.
• 33:01
  SPEAKER_02: We developed a skin swab where we take um um enough, there's enough skin cells on that skin swab, and it's taken years to develop from a biopsy to a swab, and actually then analyze your mitochondrial DNA damage at that time point.
• 33:16
  SPEAKER_02: And so that allows us, if you say your first swab is time zero, then you have an intervention or a change in your lifestyle or putting on a product, then you take that swab at, I don't know, six weeks or twelve weeks, then you can figure out actually how is your DNA damage in your mitochondria going, which obviously is reflecting the health of your skin.
• 33:36
  SPEAKER_01: Ah, this is brilliant.
• 33:37
  SPEAKER_01: Okay.
• 33:37
  SPEAKER_01: Well, we we've run out of time, unfortunately, but we could go just into that subject again.
• 33:42
  SPEAKER_01: So I'd love to get you back just to talk about that.
• 33:45
  SPEAKER_01: Uh and send me one of those swabs.
• 33:46
  SPEAKER_01: I want to do this.
• 33:47
  SPEAKER_01: So uh deal.
• 33:49
  SPEAKER_01: All right, great.
• 33:50
  SPEAKER_01: So uh this has been Skincare Confidential.
• 33:53
  SPEAKER_01: My name is Dr.
• 33:53
  SPEAKER_01: Ted Lane, I'm a board certified dermatologist.
• 33:55
  SPEAKER_01: Uh, I have had just the wonderful pleasure of interviewing Dr.
• 33:58
  SPEAKER_01: Mark Mark Birch Machen, who is the uh professor of molecular dermatology at the Newcastle University Institute of Cellular Medicine, who has done some really groundbreaking and incredible research on the effect of sun protection on uh mitochondrial DNA in fibroblasts.
• 34:14
  SPEAKER_01: And uh really the tip of the iceberg of everything that we could talk about, Mark, but thank you so much for your time.
• 34:19
  SPEAKER_01: Thank you.
• 34:19
  SPEAKER_01: Thank you, Ted.
• 34:20
  SPEAKER_01: All right, thanks everybody.
• 34:21
  SPEAKER_01: Don't forget to to give us a like, subscribe, and refer us to your friends.
• 34:26
  SPEAKER_01: And uh thank you very much.
• 34:28
  SPEAKER_00: This episode is brought to you by Skin Suticles, the number one medical aesthetic skincare brand worldwide, and the leader in antioxidant science.
• 34:37
  SPEAKER_00: To learn more, visit www.skinseuticals.com.