About the guest: Andrzej Slominski, MD, PhD is a dermapathologist and skin biologist who has spent decades studying skin biology, especially regarding endocrinology (hormones), stress response, photobiology, and more.
Episode summary: Nick and Dr. Slominski discuss: hormone production in the skin; vitamin D photobiology; risks and benefits of UVB light; skin cancer & sunscreen; protective effects of melatonin production in the skin; and more.
Related episodes:
M&M #104: Benefits & Risks of UV Radiation & Sunlight, Skin Health, Vitamin D, Nitric Oxide, Evolution of Skin Color | Richard Weller
M&M #146: Photobiology, Sunlight, Firelight, Incandescent Bulbs vs. LEDs, Mitochondria, Melatonin, Sunscreen & the Optics of the Body | Scott Zimmerman
*This content is never meant to serve as medical advice
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Episode transcript below.
Full AI-generated transcript below. Beware of typos & mistranslations!
Andrzej Slominski 1:30
I am MD, PhD, and I am both practicing physician. I am a dermatopathologist. So I read something high level of specialization in pathology slides in skin by a dermatologist, and I provide the diagnosis, which is guiding the dermatologist, or sargeron or else with therapy or excision. So this is one on the second time, also scientists and PhD. I got my PhD in Poland, in tumor biology, but my areas are diverse, biochemistry, molecular biology, Cell Biology, skin biology and narrow endocrinology and photo biologists. So these are these areas my current appointment. I am a Endowed Professor of Dermatology at the University of La Bama and Birmingham. I'm also a professor of pathology here, and my main I have second appointment, five, eight appointment at the veteran administration here in Birmingham, where I predominantly serve as a dermatopathologist, so I do the clinical work, but also I'm supported by the because there is another benefit I can apply through the veterinary installation system for the grants, and I'm supported by the VA merits Awards, which was renewed for another four years after peer review. And at the University of Alabama, I am supported by Department of Defense grants and by the grants of NIH and matching internal funding. It is simple. If you are at, say, UAB, depending on the department, you're successful with NIH or other foundation, they will support you even more, so you will be more successful.
Nick Jikomes 3:53
So So you're an MD, PhD, so you do both clinical work and you do research, and a lot of it is focused on different aspects of skin biology.
Andrzej Slominski 4:03
Yes, this is correct.
Nick Jikomes 4:05
One, one thing that I know that you've studied is you've studied the the function of hormones and the endo endocrinological aspects of skin function. Normally. When we think about endocrinology and hormone biology, we think of endocrine glands, like the pituitary gland or the adrenal glands or thyroid but to what extent is the skin and endocrine gland? To what extent are hormones being produced within the skin
Andrzej Slominski 4:32
itself? So I wouldn't call it endocrine gland, because endocrine gland, you have a gland which is highly specialized and only this, like anterior pituitary produce several hormones, like adrenals. Have adrenal cortex producing glucocorticoids, or any other classical endocrine glands, skin is organ. With the neuro endocrine capability. So depending on the environmental stress and the context, it's not only stress, but also is sensing the environment, because this is a most exposed, outer, exposed part of our body, but the part of the body of different animals through which it's a communicate with the external environment. So this is how so the external environment is not only receptive by other senses, like eyes, hearing smell, but also through the entire through the skin, just so the skin can sense the temperature, can sense the light, can sense different wavelengths of the ultraviolet, right And and also be subject to different stressors, stressors, so in reaction to the stressors, depending on the stress applied, and depending on the anatomical location in the human skin, in can start to produce several classical neuro hormones. And in fact, I published in 2000 in the endocrine review, which is a leading journal in endocrinology, with Dr wordsman review, neuro endocrinology of the skin, so which was for the endocrine community, it was a little bit shocked that the skin where we were summarizing our work, work of other people, that the skin can produce classical hormones that are produced by the endocrine glands or by the brain, Like cortical dropping releasing hormone or corticotropic Increasing factor, because they use people they say, CRF or CRA depending who say and in which context, they can produce cortical trapping, releasing hormone related peptides, such as your recording. One eurocardine, two, they produce classical and this is prohormone like propial melanocortin, which is further in the regulated way process through ACTH and further down to alpha MSH in the context dependent version, or a better endorphin, so you have opioids, and this can act locally, but under significant stress, can be released into systemic circulation, but under, as I said, under highly significant stress, and then Have a global, homostatic effect. Another hormones is which are produced in the skin. Is hormone of happiness, serotonin. So serotonin is produced in the brain. I will you are neuroscientists. So you know, it is produced in the GI but the skin is another organ which is producing serotonin. And the serotonin, also in the skin, can be biochemically transferred into melatonin another so this is a site also of another very important hormone, with that also context dependent different functions are of of melatonin. There are also several other hormones. There are glucocorticoids, Corti in the human skin. Cortisol is produced in the skin, and there is her metabolic pathway for this production, which is inducible. Because all of this production is inducible on the low level, when it is it will be very low. It will be almost below detecting but depending on the stressor, depending on the system signal, it is inducible, so cortisol, corticosterone in rodents, and then we have the expression of correct, corresponding receptors in the epidermis and different dermal structures. So these hormones will act locally to regulate the local homeostasis or to have phenotypic effects in the context dependent fashion. But if the stress is huge, can be released into the circulation and have the systemic effect. And another example there it is a little bit immunology, but different cytokines, interlocking, one, interlocking, 6d, ref alpha, are also produced, not only by say, immune cells, but produced by skin cells. And the skin cells, like keratinocytes, like fibroblast, skin. Fibroblasts are immunocompetent cells, and these are classical immune signals, but they have also consequences in the signaling on the neuroendocrine level, because the cytokines interact in one things they can stimulate, also procure melanocortin expression and processing and stimulate cortical dropping, releasing hormones so they can activate also another type of the signals, hypothalamic pituitary, adrenaliness and maybe the most classical hormone, not carbon, is pro heart. So this is is a production of vitamin D where it's it is only the skin or or or any other side of the body which is exposed to the ultraviolet B radiation, where the 700 cholesterol, which has the unsaturated B ring to double bonds on the B ring and only. And this is crucial, it's it's phenomenal in the evolution of life, how the life adapted the structure for the signal transduction after absorption of ultraviolet B at Ultra, violate a, yeah, only ultraviolet beam is being broken, and then through the photochemical and thermally driven reaction change. It's a vitamin d3 which is injected into the circulation, and it's an after activation by a two classical enzymes, is acting as active form of vitamin D, having the enormous homeostatic activity, not only on the bonds or skeletal muscular system, but also several other regulatory functions in the classical way, is acting to vitamin D receptors. And in fact, I don't know if there is an organ that does not express a vitamin D receptor. So this is classical pathway COVID, also non classical alternative pathway, which is activated by enzyme, classical enzyme, or steroidogenesis, tip 11, a one, and which hydroxylate vitamin D in different positions, producing Different active forms that I also subject of of modification by other cytochrome enzymes. So we know at least that right now there is at least 18 attractional hydroxy forms of vitamin D in addition to the classical described in the classical pathway, and many of them are circulating in the human body and also murine. We didn't publish about the urine, but we know for years, because we use some as a controls, experiments and say, have similar effect, like classical car syndrome, but also sometimes different and also similar but different mechanisms of action, because not only vitamin D receptor is is the target for the regulation, but also several other receptors which we have discovered. It's like lxR, which is deliver its receptor. Like Aryl hydrocarbon receptors are a example of the receptor already, like orphan accent receptor alpha, gamma, with this one, they act as inverse you want. Yes,
Nick Jikomes 13:51
okay, so, so there's a lot to unpack there. Basically it sounds like so the skin is not an endocrine organ, like, like an endocrine gland. It's not fully specialized to only specifically produce and secrete hormones, but nonetheless, it does have the ability to produce and secrete and respond to various hormones and related signaling molecules, and it sounds like a lot of that has to do with the fact that because the skin is our interface with the environment, it is going to encounter many different forms of potential stress, physical stress, changes in light, temperature and so forth, pathogens that might get in through the skin barrier. And because it has to deal with all those stressors, that is part of the reason for why it it can actually produce certain hormones.
Andrzej Slominski 14:38
This is correct and and it has certain pathways, like primordia in the primordial form, which are embedded into the skin, which we have this organization, also on the central level. I'm giving the best example on the hyper. Adrenal axis, which is a really very beautiful axis and directing the responses of our body, perfect responses, perfect organization to stress, and which really followed the concept of hand salience and others will evade. So you have hypothalamus producing corticotropin, really, and he will appreciate this as a neuroscientist, hypothalamus producing corticotropin, releasing the hormone or factor, and then which center portal circulation go to the anterior pituitary, act on the melanocortin receptor, type two, in the anterior in the cortical graph, stimulate release of ACTH, and also stimulates the PMC production and processing tract has to be replaced and the act in the collation is going to is a classical adrenal cortex, and acting now in the anterior pituitary, we have cortical dropping, releasing hormone receptor, type one, with the MC two, I went too fast, type one, which after activation, release of ACTH, ACTH circulation, adrenal cortex, action on the melanocortin receptor, type two, which is a very specific for ACTH, recognized predominantly and Almost only ACTH and send release of glucocorticoids in humans, cortisol and different related species in rodents, majority corticosterones. They do not produce cortisol, and just counter action against the stress and counter action against the immune immunosuppressive, immunosuppressive effect and modification of the global body status and this beautiful feedback mechanism, cortisol is stocking production of CRH, stopping the PMC and production of of ACTH. Very beautiful, intellectually fascinating, access. And really I was the first one. And with the no data almost at the time, maybe the PMC is in the skin, CRH is in the skin. So like almost 25 years ago, we formulated the concept that the skin has the HPA axis system in response to stress, and that it has adapted this from the central level, because also you have this diverse stressors, actually. So this is organized the same way
Nick Jikomes 18:11
I see. So it sounds like what you're saying is so classically, when we think about stress and stress hormones, we typically think about the hypothalamus and pituitary. There's a system set up in that part of the brain to release stress hormones, both within the brain and throughout the body, in order to prepare the animal to respond to stress. What you're saying is that there's actually kind of like a similar setup at the molecular and cellular level, actually in the skin, in terms of a stress response mechanism, exactly.
Andrzej Slominski 18:37
And I will jump a little bit off site. But there is another stress response system, which is activation of adrenergic system, just the release of the catecholamines. This is another system so in the skin the skin cells can also produce catecholamines. They not only released from the nerve ending, they are produced by the resident skin cells, but the production of cattle Hala means it is by by other people is we confirmed we can find this so, but let's come with the HPA axis. So, so the similar system is operating in the in the skin, and once we have more and more data, because we were also funded study PMC in the skin and CRH receptors in the skin, so we suddenly started to realize that there is diversification. So this axis may not be as classical context dependent. It can be theory, H receptor, PMC, cortisol, but depending on the stressors, it can be really so called, fragmented so and regulated in the different way. So in 2007 I have. Published commentary in the Journal of Clinical investigations under the title nervous breakdown in the skin. I can send you this commentaries where really I have changed my mind just by coming into conclusion. So this is not the skin adapted from the central axis, but the central system has adapted this primordial responses to stress and perfected on central level.
Nick Jikomes 20:38
So it sounds like you're saying from an evolutionary perspective, the sort of basic primordial stress response system that we see in the brain and the hypothalamus probably has as a precursor existed in the peripheral tissues like the skin of animals
Andrzej Slominski 20:53
or integuments, because The central nervous system back far in evolution was not developed so, so it was through evolution. Everything was perfect. What we have right now is absolute perfection. Current environment, if someone believes to evolution, I believe and so it's so it is so primordial stress response system has used the same molecules, the same receptors and signal transduction and shutting off mechanism and
Nick Jikomes 21:34
see so basically, you're saying there's a very old system to respond to stress that was that involves the release of things like hormones, things like what we normally think of as neurotransmitters in the skin, and this can be found even in organisms that don't have a very well developed nervous system. This is,
Andrzej Slominski 21:53
this is correct, and this is what, and this is what has driven me in this commentary. And it was surprising that say, really, let me publish this. And if JCI was preparing for me to schematic figures, I was by hand drawing sending to them, and they were preparing, this is this. And finally, finally, and I think it was perfect. So either was that this is because everything is in the skin, so the cells are closed, so all of this interaction are very close, and this is somehow getting diffused, like diffuse endocrinology or balkanization. I don't want to be politically incorrect, balkanization, we know. What does it mean? What was happening in the Balkans, but like balkanization of the certain orders, but everything has the logic is context dependent or stochastic in nature. So this system, through the evolution, was because it was almost perfect, and it was perfected and developed in the central HPA axis, which differ from the skin, because there is anatomical dissociation. You have hypothalamus pituitary anatomically dissociated, so the signal can go very precise, and then you have another dissociation between pituitary and an adrenal gland. And then you have very important element, which is in the HPA axis. And it has to be also. It is not considered in classical way, but I think in the educated well, it must be concentrated, say immune system, because immune system on the beginning was primordial, so everything was communicating. So the immune system also is part of this HPA axis, because it communicates with with the pituitary, it communicates with the other animal glands, and it's getting shut off if you have this inflammatory molecules produced by the HPA axis, final reading of HPA Axis partition, but also intermediates like ACTH, is also acting as immunosuppressor, so all of these elements become separated, and then you have a perfect algorithm of our body. So I think this is, this is very educational and and that skin, another element is just the Biogenics and the melatonin. So this melatonin energy system, but with the melatonin energy system, there is also a long evolution, because on the beginning the people predominantly thought that it is produced only in the pineal grant when I was publishing papers on the. First papers demonstrating that the melatonin can be produced, and we did very good biochemistry. It was really to provide the proof in the classical way, just when you look on precursor and progress. So
Nick Jikomes 25:15
it sounds like you're starting to say so, not only does the skin produce stress hormones and have sort of a stress system that is, in essence, a primordial version of the stress system in the brain, but it also produces things like melatonin. So we normally think of melatonin as being regulating our circadian rhythms and being secreted by the pineal gland of the brain, but this is, again, an example where the skin can also do something similar here exactly.
Andrzej Slominski 25:41
So it's a melatonin. I was the first one to show the production, and I was facing scrutiny because one of the directors of NIH who might know, I will not say, What, so he was sending emails to me. No, it must be artifacts, and I so I was sending back to him. No, no, this is not the artifact. We have a mass spectrometry data. So he at the time, he never admitted, Oh, I see that you want to start melatonin the skin, but he never, never agreed with me at the time. But it's no question, is so
Nick Jikomes 26:18
so light is is it dependent on light sensing in the skin, similar to the way that melatonin production centrally depends on light levels, probably
Andrzej Slominski 26:27
light may play a role, but most likely is peripheral, which is independent on light. And it is really the production is for, probably for local purposes, because locally it will be monumental production at the production of melatonin, once you start to analyze the property of melatonin, because other properties, which are recognized and which Were championed by Rath rider is the anti oxidative properties of melatonin by itself as a molecule, but also is melatonin is inducing the anti oxidative protective mechanism and the DNA repair system. So once you start to put this together, it will be logical that the melatonin in the skin, the function is protection. I see ultraviolet and sun, which is continuously damaging the skin, and you have production of the hormone which is counteracting its effects. So
Nick Jikomes 27:36
So melatonin is an antioxidant, and it's not only involved in our circadian rhythms, which is how, which is what it's most famous for, but it's also involved in things like DNA repair. So in response to an environmental stressor like UV light, which can cause oxidative stress and DNA damage, melatonin is actually being used locally in the skin to help protect against that, yes,
Andrzej Slominski 27:59
or to restore the hemostasis. In fact, you know, there are really many areas to research, and one of the pure speculation which you can come out, okay, you have this stress UV during the summer and now during the night, you have to restore, protect, to repair the mechanism, because otherwise you have the destruction of the organ. So in the lecture, but we have to do more. Data and money for such research are not as available. And then during the resting period, it is restoring, repairing the DNA pushing cells, which are not destined for repair, for reparation, because they may be precursors for the cancer cells, for apoptotic pathway. So the different mechanism and melatonin and melatonin is doing this in the scheme, which is an, I can also say the connection with ultraviolet. Said, for example, we know it's a whole pathway for serotonin and then melatonin. It starts with a tryptophan hydroxylation. You will express tryptophan, simple tryptophan, to ultraviolet radiation. You can generate five hydroxy tryptophan when, if there is the carboxylase, an amino acid, so it will be changed into xenotronyms, so there are also elements of the physical, not only enzymatic, physical, chemical interaction of the light or the short wavelength of the light, then, with the melatonin, by itself, is metabolized through the kenoric. An endolic pathway, but let's say Kenora pathway, which is production of afmk and AMK, which are also potent antioxidant. So these are different molecules which probably will act on different receptors, but also they met. Metabolism or degradation of melatonin is activated also by the UVB. Interestingly, to produce afmk and AMK, you don't need to have there is enzymatic battery, but you don't need to have enzymes. Ultraviolet will do this,
Nick Jikomes 30:42
I see so just the exposure to UV radiation can
Andrzej Slominski 30:47
put the environmental to peak, environmental stressor can do this so you have production of other molecules under the stressful, damaging condition, which are also counteracting the biological effect, because they induce the DNA repair mechanism. There's a lot of
Nick Jikomes 31:13
built in biochemistry here whereby the exposure to a stressor like UV radiation initiates the creation of molecules that serve protective functions. Melatonin being one of them, I want to ask you a little bit more about the photo biology of the skin. So one of the things that I think is most famous in terms of how the skin response to light is that we produce a lot of our vitamin D in response to UV radiation exposure. Can you tell us a little bit more about how how does light induce vitamin D synthesis, and why does that happen? What is the vitamin D actually doing for the skin and the body?
Andrzej Slominski 31:46
I think this, this was, I don't want to really put the speculation, because the role of the UVB was established in the production of vitamin d3 for over 100 years and 100 years ago. Column, I think the vitamin D production of and discovered that it is and the UVB is inducing production of vitamin D. There was a Nobel Prize for the production of vitamin D, and it was at the time in the in the 20 in the 20th century, it was really important rickets. And once you know, then you can cure many, many chronic and devastating in outcome pathology. So it is a simple photochemical reaction, suddenly hydro cholesterol, which is a final intermediate in production of cholesterol. So cholesterol very important component of membranes and very important components of the body lipids, I think crucial, because cholesterol is also precursor the for for the metabolic transformation into precursor to pregnant alone, which is all steroids.
Nick Jikomes 33:17
Yeah, it becomes, it's the precursor to all the steroid
Andrzej Slominski 33:20
levels with vertebrates. Guy, salt. So this record, sorry, seven decade cholesterol, and it is producing the skin, is in other organs. And seven decade cholesterol has the unsaturated B ring. This B ring is reduced by seven Delta reductase to produce cholesterol in the skin situation, it's a little bit different, in particular in the epidermis, because it can be but if it is exposed to UVB during the summer, when UVB is in the spectrum of the solar radiation, the bearing is up. And this is a, I think it is physical, chemical beauty in biology. For me, it's one of the most beautiful photochemical reactions, which was adapted by all the vertebrates living on the sun, so it is absorbed by its absorbed this energy, and B ring is broken and is changing the configuration which is accelerated under the temperature, and It can go into the configuration of vitamin d3 which then is ejected and then is activated in the heteroxylation on the carbon 25 in the liver, but also locally. So MVP transforms
Nick Jikomes 34:55
this version of cholesterol into vitamin d3 and then what. Then what does the
Andrzej Slominski 35:02
vitamin d3 do? Vitamin d3 enter the circulation, or is staying locally, and his parts are enzymatically activated and said through two sequential hydroxylations in position 25 and then position one. So it will be 125, Dieter, oxy vitamin d3, which has the fundamental role in the regulation of calcium metabolism, about the bone formation, musculoskeletal system, but also regulate other, many, many other functions which are diverse. So this, this is one part, of course you can supply South UVP, if because UVB, it's not a big brainer. It's like Dr Jekyll and Mr. Hyde, depending on the context, is good. Vitamin D is bad if you expose yourself too much, depending on your skin pigmentation, the skin cancer is guaranteed.
Nick Jikomes 36:17
So UVB is bad because it can promote skin cancer if you get too much exposure. But it's also good because it's doing a number of other things that are beneficial Exactly,
Andrzej Slominski 36:26
exactly so so is with a vitamin D, and of course, you can just prevent exposure from the UPP by oral supplementation. But oral supplementation of vitamin D, you go through, say, Gi, go through the liver, 2500 selection in the liver. And this, it is like, like targeted must of this into this 125 classical pathway I have discovered, and we have discovered, together with Robert packet from Australia. So there is alternative pathway and enzyme simple and a one which recognize which cat, which transform cholesterol to pregnenolone, starting stereo Genesis also recognize vitamin d3 and it's hydroxylating in different positions, producing several metabolites, and this are also biologically active locally.
Nick Jikomes 37:35
Perhaps. Are you saying that? So the vitamin D that's produced in the skin via exposure to UV radiation is a different version of vitamin D than what's produced in the liver.
Andrzej Slominski 37:45
It's the same, okay, the same. But also it show how accessibility and how our body can can using same precursor really make different balance. For example, if you take orally, majority will be hydroxylated in position 2525 hydroxy vitamin d3 is not recognized by 1181, so once you hydroxylate In this position, so it is classical pathway. There is no other pathway. For activation, but if you have unmodified vitamin D, so if it will bypass the liver, it's not hydroxylated or produced in the skin and inject it into the circulation and go, for example, to the adrenal gland or in the skin, because simple 11 is also expressed in the skin, and it is inducible by UVB quite the way. So everything context dependent, so it will activate vitamin D in different producing the different hydroxy.
Nick Jikomes 38:55
So the way that your body gets vitamin D dictates what it actually does with it. In other words, the vitamin D that you get through exposure to UVB radiation, if you walk outside in the summertime, is going to result in your body using the vitamin D in sort of different ways to some extent than if you were to take an oral supplement, to
Andrzej Slominski 39:13
some extent because it will be from skin, it will be activated but but this is not the end of the story. With 700 cholesterol and this photo biological transformation, because under prolonged exposure to UVB, so you have higher energy, more damaging the configuration, because this photo chemical is changing from from d3, pretty three into tax sterol, which is really very, very difficult to study, because it undergo easily auto oxidation, so it's unstable. So we we studied a little bit very. Very difficult. We come to conclusion, conclusions, but we moved into lumister because there is another component lumister So prolong, and this is the most stable for prolonged formation, such as bearing is being received in different configuration for lumister and before our discoveries, before, 20 years back ago, everybody thought that lumens, roll is inactive compound, that this is how the nature has formed if you have too much UVB. So the people who were are afraid also that if you use too much vitamin D orally, so you can produce hyper calcium, you can even kill the person with the dosage. And never happens with the skin, where this monumental concentration can be produced. So this is an, it was intellectual, that is stimulating hypothesis. Well, this is self regulating system, UVB, or UVB, not vitamin D, but luminster on. And this is like a sink, protecting from the intoxication by vitamin d3 but let's say billions years of evolution, if something is spawn, cannot be useless, because this is economy of the life. So it must be used for something. And what we have discovered that the lumisterol is not that that air product. It can be hydroxylated by sip 1101, and by sip 27, a one to different hydroxy derivatives, which suddenly are biologically active. We tested this in the predominantly skin cells, and they act on the nuclear receptor. They do not act on the genomic site of VDR. They do not but they act on the Alexa receptor. They can act on the retinal orphan acid receptors as inverse organs. They can act on other nuclear receptors and have the phenotypic effects so and which nobody was testing before we did, lumisterol is circulating at high level in your body. So if enter the circulation, then it will become available for activation, either by sip 11 a one, or by sip 27 a one, which is expressed also in the liver. And about this, I will do, what the consequences? So you have activation, and you have, I'm setting, and I'm not afraid to say, production of new types of hormones, because they will act, hormones fulfilling the definition of the harms through receptor mediated mechanisms. So in this context, not only vitamin d3 on, which we really very much and everybody is focusing and is overlooking or is not knowledgeable on. This is lumister all and the lumisterol similarly, like vitamin d3 would act as a prohormone, and I think that there are consequences and tip of the iceberg, because we started the study, and question is always coming like you are vitamin D deficient, inefficient are sufficient by measuring the levels of this hydroxy derivatives of vitamin d3 but you're forgotten, for example, about the luminister role, which is also will be the consequence of high exposure to The UVB. And if it is activated, must have some biological activity, which we still don't know. It is like that i COVID, in COVID. So basically,
Nick Jikomes 44:11
basically, the total amount of UVB, another new, hot one, yeah, the total amount of UVB, another light that you're exposed to will dictate the specific pattern of different pro hormones, and therefore hormones that will be made in the skin and elsewhere, vitamin d3, just being one of them. But if you're exposed to high enough levels of UVB, you actually start to create this other pro hormone molecule that will have different effects. You've got it. What about so everybody knows. Well, I want to talk a little bit more about light sensitivity and photo biology of the skin. So obviously, you know, UV radiation is famous for inducing mutations in DNA and stress in the skin. What about the skin's ability to detect other wavelengths of light? People are starting to talk more about. And near infrared wavelengths of light. How does the skin detect other wavelengths of light that potentially don't have damaging effects, but have other types of physiological effects? Yes, there
Andrzej Slominski 45:11
is these. Are a new areas which are which are developing, and unquestionably it is accepted. For example, opsin. Opsins are really are expressed in the skin cells, expressing melanocytes or keratinocytes. And there are mechanisms of the detection of the light, detection on the shorter like blue light or other further long wave, and they have the phenotypical effect. For example, light will have the effect on the melanocytes function, but, but this is still like a very I'm not venturing into this, I realize, but because it is very difficult to investigate the field, there is a fact. There are light receptors, unquestionable. But to nail down this, what is happening and how it is regulated, taking into consideration because let's focus, because our focus will be the human skill. Let's focus so there are different anatomical side of the skin, face, even on the face. Then you have the torso, you have the back, you have the hand, you have the feet. You have this different type of the skin, Acral skin, without the adnexa, so they they may have different mechanisms of the detection of external signals. And also the mechanism of the light detection. With the light detection is not easy to study. And for this good funding is, is required. Unfortunately, the funding is, is there is less and less funding by NIH and by or NSF and reviewers, at how NIH always is saying, Well, we have new hypothesis, and the best is an asset, because are the most, the most, really, the good, really review process, they look for new ideas and and new hypothesis to be tested. Unfortunately, National Science Foundation, if something is good close to the human will say, sends to NIH. Once you go to NIH in something is too theoretical, you will be rejected. And there is no money to really just study and understand the mechanisms. So
Nick Jikomes 48:02
certain aspects of Photobiology are hard to study, in part because the funding is hard to come by.
Andrzej Slominski 48:09
UVB. Also, I was fortunate. Why? Why we were because we could do the connection. It is not through vitamin D, but UVB acting on the skin, and we did in the urine system can activate Central, Central, not skin Central, so brain sense UVB through the pathway hypothalamic axis, UVP could activate the propio melanos signaling in archways nucleus. So then we had these mechanics are different UVB and still unexplained, and we can hypothesize, but there is a need for more experience on this can activate. We did the experiment with animals, you expose animals to the UVB, the skin, and then could shut off within 60 to 120 minutes, shutting off completely immune response in splenocytes in the spleen cells, so spleen somehow detect the signal. So some
Nick Jikomes 49:25
somehow the body's detecting light is going properties
Andrzej Slominski 49:29
through a neural transmission. So you're a neuroscientist, so you know too fast to go through hormonal must go Yeah,
Nick Jikomes 49:37
so within seconds, the body can detect light in the periphery and use neurons to communicate up to the brain, presumably, and then out to other organ systems faster than a hormone could get there,
Andrzej Slominski 49:49
and I must tell you, the spleen. Remember, because drink after 24 hours, because we have to set up in 48 hours. The immune responses of the splenocytes were muted. So it's not only you have rapid but there is memory of this for certain period of time. So these are fascinating areas, because I think they could help in the therapy, very, very simply, very economical therapy, without many drugs, biologicals, with costs, enormous amount of money, just good photo therapy, educated photo therapy, because we know what is the danger. We acknowledge skin cancer in several neuro generators, or autoimmune diseases like rheumatoid arthritis, like a diabetes, like multiple sclerosis, and there are correlations, say, with the like UV exposure to the UVB and just presentations of these diseases. So this could be simply applied in the in the educated way, and then I will have to complain how I'm funded by NIH If, on the other side, wherever I send the grant above the UVB, there is always this third criteria, where he wants to study the cancer on gene acid therapeutics, he must be crazy, so you will get the score. You will never be funded. Or so we say, well, study your vitamin D compounds and not the carcinogens, but National Science Foundation, at least, we went up to certain level, was very open, because it's a new bio but National Science Foundation doesn't have a sufficient amount of money. One
Nick Jikomes 51:58
thing I want to ask you about is so when people think about skin cancer, they think about right, your sunlight exposure, your UV radiation exposure. What are the most common forms of skin cancer, and are they primarily caused by UV radiation exposure, or can skin cancers arise by other means,
Andrzej Slominski 52:16
primarily, primary factor, which is inducing skin cancer. And the most frequent, and the most frequent among any cancers are basal spurs, basal basal spur. Basal cell carcinoma, number one second is common, sir carcinoma of the melanocytic origin and undeniable, clear cut correlation between the UVB exposure. Why? Also, there is not needed to be a rocket scientist, but DNA. Is a chromophore is absorbed by UVB and UVB induced damage, and there is signature for the UVB damage, and this in those mutations and also UVB generate immunosuppressive environments. Probably for good reason, immunosuppressive every moment. Because, if you I will not speculate in society. And so everything will make a perfect condition for the formation of basal exclamation, I see.
Nick Jikomes 53:37
So the UVB is not only able to induce mutagenesis, to mutate the DNA, which can lead to cancer, but it also suppresses the immune system, which might otherwise get rid of the cancer cell before it forms.
Andrzej Slominski 53:49
Yes, exactly, exactly. So, so, so everything in this place. So for example, it's a vitamin D and melatonin, when we start to look at this molecule, so we see what this UVB is doing. And then, let's say vitamin d3 and some beautiful molecules, because they only produce that's the UVB, nothing else. There is no Chem biochemistry in this in the skin. So the nature has really adapted this molecules first sense the danger and the second counteract So, and this is why, for example, vitamin D, active forms of the vitamin D have photo protective activities. Say induced anti oxidative responses, and say really induced DNA repair mechanism, and is an inhibit cell proliferation. So, yes, you induce the. Cancer. But there is this molecules after activation, will counteract this process of carcinogenics. And again, everything is concept dependent, because different people have different
not the capability, the propensity to develop. It's a concept depending on the genotype. And there is different that you are more successful or not. And another which we see fanatic, fanatic, let's say, and this is a skin pigmentation level of skin pigmentation, people with the lights, skin pigmentation without facultative melanin production, which can be induced by UVB skin cancer, guarantee people with a darker skin less probability of the skin cancer. Yes, so you have the probability you cannot, and it is, unfortunately, it's sometimes the pathologists ignore and can misdiagnose melanoma in the person with black skin, very black skin, because somehow he shouldn't get it. No, they also get it, but probability is much, much lower. So, so
Nick Jikomes 56:19
part of the function of skin pigment is actually to mitigate some of the stressful effects of UV light. Yes,
Andrzej Slominski 56:30
and and with the humans, we have plenty of the exciting when how the gradient of skin pigmentation you go to the towards the equator, like skin and the big experiments performed by the British Empire by settling the Australia, the highest level of melanoma incidence in the world, where in Australia,
Nick Jikomes 56:57
because you have light skinned people that moved into an environment meant it's not only
Andrzej Slominski 57:02
the light skin, because we have the, let's say about that pigmentation. You have Scandinavian which have a lower level of pigmentation. And you have, for example, I can be politically incorrect, because we speak science. We have the Irish people who have a lot of fear, melanins, this red pigment that one of my friend, he said Canis in he was Italian, Canis. And he was saying always to the Irish, we said, you you black people, but you red people. You are not light people. You have too much fear melanin. So the level of female in they have, it will be like Africa in Africa, but the pigment melanin is protecting. Pheomelanin is really bad news, because after the light, or after different wavelengths of UVR, is producing this oxidative environment, producing the mutation it generate. It is, it is really one of the factors which really contributes to the melamine melanoma Genesis.
Nick Jikomes 58:12
So you're saying that actually, the pigment that fair skinned, red headed people have actually in response to UV radiation. It's not only that you'd be in the presence of UV radiation, but that pigment can produce oxidative stress itself, right, right?
Andrzej Slominski 58:26
Pure melon. It's so to be better lightly pigmented, like some Scandinavians, than to have this red head phenotype, and you think that, yes, the skin is white, but this is pure melon. This is a lot of melanin. So he's not this person is not lightly pigmented. Is not white, but,
Nick Jikomes 58:47
yeah, they have light skin, but they have a lot of pigment. It's just not a
Andrzej Slominski 58:52
dark it is a bad pigment. So for me, always it was really challenging through the evolution the pure melanin in the human population, and this red head phenotype should be eliminated because increased cancer for some reason, not so. This is another interesting question to study. What is the use of fuel melanin, or at least some pathways connected to the fuel melanin? Just which make you advantageous.
Nick Jikomes 59:29
It has this, it has this disadvantage of creating a pro oxidative environment, response to UV light. But it must be serving some advantage at a high latitude, because it became common there,
Andrzej Slominski 59:38
right, right. I fully agree you got it.
Nick Jikomes 59:43
What about so I want to talk about so obviously, the skin response to light, as we've talked about it, responds to UV light. You can induce, obviously, mutations and cancer from too much exposure to UVB. But UV light also induces things like the production of. Antioxidants, vitamin D, the other things we talked about, I've also previously discussed on the podcast, that UVB can liberate nitric oxide, which has cardiovascular benefits. Are there any other benefits to Weight, Light, exposure to the skin that that tell us that we should get some sunlight, but just not too much?
Andrzej Slominski 1:00:20
I think that there is more than vitamin D, and this molecules, because UVB as this button stressor, and this is how we drove our hypothesis on the central HPA axis, can regulate how much does this in the very regulated manner, like inducing sending hormones or sending the cytokines to activate the central organs like the like pituitary or adrenal cortex, because ACTH or churro Carter, UVB inducing a lot of CRH production of skin or urocortis brain hormone hypothalamus, or interlinking one, which can also stimulate the production of CRH. So this signals can send to the difference of the regulatory organs, such endocrine organs, they can amplify and they can reset homeostasis. So it is not only vitamin D, not only melatonin, there are several other hormone products in those by, say you the ultraviolet light in the skin, which can reset the homeostasis in the most perfect system, which is beneficial for your health. So and then consequences just less, lower probability of developing autoimmune diseases, except lupus erythematosus, which is really induced and is without aggravating, But so also like rheumatoid arthritis or ulcerative colitis, Crohn disease, so there are several. So I don't think that there are enough studies. And I also meet with photobiologists, and everybody's facing this problem. You want to study this? They will tell you, well, interesting. Thank you. We are not interested in your study because you induce the cancer. And it's it is unfortunate, but phototherapy, because what we have, we can really right now with this new light sources with narrow bands or specific led so specific wavelengths you can use for therapy of different diseases in dermatologists, using the therapy, for example, of The cyrosis, but less and less because of the the because the biologicals to cover, the biologicals have their own disadvantages and are extremely expensive. So, so Photobiology, if Photobiology and photo biological approaches for a treating, not only cutaneous diseases, but photo for treatment of systemic diseases, is deserves attention. Not only attention, deserves a support and publicity. And I hope that you will support this, because if there will be more and more people saying, no, no, we want more research in this area, finally, you sent the grant and they will listen. You are not sending back. We don't want you to start the concerto. Genic factor, yeah,
Nick Jikomes 1:04:10
what is your what is your general perspective on the use of topical sunscreens to avoid sunburns? Obviously, it will help block out the UVB and help prevent sunburns. Are there any potential downsides that topical sunscreens provide? Can they mess can they get into the skin and cause other effects? Yes, there
Andrzej Slominski 1:04:31
are different products for this. For example, myself, if really I will go on the lake and the kayaking or something like this. No question, I put the sunscreen, but I also put the t shirt and hat out how it is very uncomfortable because, because sunscreen will not protect, protect, because they have a certain timing, and you have to reapply. Don't know when to replay precisely, because how they measure the sunscreen by redness, just so, and this SPF factor by redness, and the redness is nitric oxide production, and nitric oxide production with UVB, and so you really measure on the UVB, but there is also UVA So, and really you don't know how much, how long, so you will be exposed some time, if this is not complex block to extend that, not even realizing of this wavelength, longer wavelength like UVA, which have also oxygen, induce oxidative damage and and this will accumulate.
Nick Jikomes 1:05:51
Are you saying that I was topical? Are you saying topical sunscreens, mostly blackout, UVB, but not as much UVA? Yes.
Andrzej Slominski 1:05:59
Okay, and then so there is so the best one is, really, they will block completely. But let's say everybody is educated, everybody knows about the sun and is taking educated risk. So wherever possible, you put the Sanskrit. But if, well, if there is no, really other possibility. But the most important is long sleeves had out of the sun, not too long in the sun, because sooner or later, it will be, it will be damaged, and some of the sunscreens, they have these different vehicles and the active products, there were some of them which are
Nick Jikomes 1:06:50
genic, so some of them are mutagenic. Where
Andrzej Slominski 1:06:53
in the past, I know, so I don't know now, because, and I don't want to say, no, no, absolutely not, not. Now, everybody is doing perfect jobs. They have tested. But they were were, and it's in the past, they were study on this. So, so, so it has to be perfect and and common sense is, is, is every educated person knows what is the sun, what is a benefit, what is a danger, and we have to do this in the very educated way, and to to really just adjust to our phenotypes, so level of pigmentation, but even you have the utan and you have a better pigmentation, you may have the mutation, like in the melanocortip type, with a receptor which will not affect the pigmentation, but it will affect antioxidative responses, so you will be more prone to to damage than the same person with the same complexion. So you look on the phenotype, the same phenotype, but this guy has this mutation, so he will have a higher probability of the of the skin cancer. So everything, everything has to be done in the educated well, and I assume that everybody is educated, and if someone is over exposing himself, it is just one choice. How overexposing to the UVB, because probably some of the people like UVB, and here is addictive effect. And the addictive effect is because of the opioid production.
Nick Jikomes 1:08:46
So opioid opioids can be induced, yeah,
Andrzej Slominski 1:08:49
better. Endorphin is UVB induced, broken melanocortin, and then processing to better, endorphins also have shown, then you have another encephalitis, better, low encephalos. You enkephalins,
Nick Jikomes 1:09:03
yeah, another type of endogenous opioid. So,
Andrzej Slominski 1:09:06
so this is, I don't know what is a mechanism which, because we don't study this with a serotonin, but also UVA can, in some group of, yeah, several started clinical study, done clinical trial, done in German, even I cited in my review, and I read very carefully they were studying attendance to the people in the sun tanning boots Explain suntanning, they have minimal UVB, President, UVA. So people go to look nice done, and some are and so some of the people are getting addicted. So they like more, and they even demand that they want to go more to this.
Nick Jikomes 1:09:56
Santanic people addicted to sun tanning. Yes.
Andrzej Slominski 1:09:59
So they started to measure different hormones. They measured serotonin, athletes. They wanted when you go through entire population, which was in the sentence, there was no difference, huge variable. But you when you sub stratified, the people who come and go nothing, and the people who wanted to go again and again and suddenly, the people who were like neutral serotonin didn't change. The people who were getting addicted, serotonin level in the serum up. I
Nick Jikomes 1:10:40
see. So people are different in terms of how much serotonin is induced by their exposure to UV and the ones that produce a lot get addicted to it. Basically,
Andrzej Slominski 1:10:47
yes, yes, exactly. So there are different mechanisms and different we have caterhala means we have the serotonin hormone of happiness. We have the opioids. With opioids, we can imagine how addictive can be. So, so it's but I think that this is a probably, probably this mechanism we're developing, and for the reason, through evolution, again, in the support of the public so, so they will start to understand that started the ultraviolet B on the human skin and homostasis is important,
Nick Jikomes 1:11:28
yeah. What about are there any negative give
Andrzej Slominski 1:11:31
us the money, we will solve the problem and provide the answer,
Nick Jikomes 1:11:36
yeah. And of course, today in the modern world, people are often spending less time than they would otherwise. In the past, have spent outdoors and natural sunlight. So people are spending more time indoors and in getting artificial light from LEDs and technology, and they're spending less time getting natural sunlight in the morning and at different phases of the day. Are there any consequences, negative consequences for skin biology to natural light deprivation.
Andrzej Slominski 1:12:09
Well, it is controversial of the topic, because if I will start to promote ultraviolet, the dermatologist will crucify me. They say what you are talking so I will be very careful with the statement. And also this is under study, so it requires study, but let's say there are, I will answer it this way, epidemiological data, rheumatoid arthritis, multiple sclerosis, two devastating disease us and our science know what is a multiple sclerosis, and I would prefer to have a skin cancer, because we know an exercise that have undergoes such devastating it's more treatable. Yeah, it is devastating. And I had a friends who really had multiple sclerosis. I was advising him just go with the high dose of some vitamin D. And he was highly educated and through I don't want anything. There is no hope for me. This is the type of the disease. And let's look. You go towards the equators, more UVB, more exposure. You don't have it. You go further further north, suddenly the intensity is increasing. And there are epidemiological data which shows that UVB is beneficial, and with the presentation for multiple multiple sclerosis. So, so this are still how important, of course, the homostatic, homostatic capability of our body, so enormous. So you will not see like with the gene mutation suddenly, but you will see this different type of the diseases, this dysregulation of the immune system and leading to, depending on your genotype, to different Chronic, chronic diseases. So I think that our technological advances help our life, but also they have unwanted consequences, and we have to realize and we have to educate, be educated, and self educate, and to be open for the new new fundings, because many things were under appreciated, and I think the same with the light exposure for the skin, light will have also a beneficial effect.
Nick Jikomes 1:14:54
What? What are some of the things that you're working on today in your research? What are some of the questions that you're asking about. Out skin biology,
Andrzej Slominski 1:15:01
it's a prominent area right now is we're starting just new pathways of activation and mechanics of action of vitamin D, which is alternative pathways and with the phenotypic reading, is aspect of Photobiology, just photo protection and against the current Genesis, because it's very practical. But also we study the mechanics of action which other receptors are activated through this new molecules, and this would have also consequences on the different diseases. For example, I am pathologist, so I have to understand mechanics of action and etiology and natural history of the disease of different diseases, but I see the applicability immediately. Unfortunately, I'm looking for collaborators, because I don't have enough expertise, and this expertise not close to me, like to study the effect of this compounds on systemic levels, like diabetes, like atherosclerosis, like metabolic syndrome. This is something which is affecting millions of people, and these are the chronic diseases, and why I want to study this, and why it could be good, because they can act on the liver. It's a receptor. This is one, one receptor, if they are conscious receptor, and we know that they can do some, some metabolic reprogramming. Oh, so this is what we are doing. We're doing this. We wanted to study the ethical trap violet. I wanted to resurrect and with the multiples sclerosis and also with the rheumatoid arthritis bus, bus, as you can imagine we, we got the cold shoulder. So, so we, we focus on vitamin D and lumin sterile. And I think sterile is becoming something very important, because I promote, and I believe that it is, in fact, pro hormone similar to vitamin D, and consequences of this, we would need to know, yes, if you are insufficient with vitamin D, can lead to different pathologists you want to have proper lever take oral but nobody knows If you are deficient in luminster role. And lumin sterol is a signal of the exposure to the UVB, whether you need to also to eat as a supplement luminster role in order to have your body healthy. And if yes, up to least which level, those are quite challenging questions, interesting.
Nick Jikomes 1:18:01
Yeah, so lumisterol. So this is the thing that's produced from vitamin D in response to considerably high levels of UV exposure. And we know very little about it, basically
Andrzej Slominski 1:18:10
ready for it, because there is this photochemical reaction which go in certain reversibility. So it's channel link it to lumin Saro, because vitamin D on one side on site. Yeah,
Nick Jikomes 1:18:26
we've covered we've covered a lot of ground already. Is there anything that you want to reiterate, or any final thoughts you want to leave people with about the skin, especially things that people might not appreciate about what the skin can do?
Andrzej Slominski 1:18:40
I think that we COVID, we can summarize that the skin is not only Sarah wrap just protecting us from the environment and preventing loss of the water, but it is dynamic. And biochemically active, or gap, which is sensing environment, and depending on because it has to go through the millions years of abortions, there is no place for the for the trial and error. It was done hundreds, million years ago, and develop sensing properties, just sensing different signals, translating them into, say, chemical messengers, which induce biochemical pathways or induce networks like a computational networks like the skin start to compute the signals, computing and react, reacting against the important to protect, or reacting on the positive signals of the environment, like more and more UVB. D and vitamin D and sending this biochemical signals into the body to reset body homeostasis to be adjusted to the environmental change.
Nick Jikomes 1:20:14
Yes, the skin is not just a physical barrier. It's not an inert protective layer. It is a protective layer, but it's dynamic. It actually senses the environment, performs computations and signals to the rest of the body. Yes, exactly,
Andrzej Slominski 1:20:28
exactly, so with high computational capabilities.
Nick Jikomes 1:20:34
Well. Dr slaminsky, this has been fascinating. Thank you very much for your time again, and I look forward to talking to you again in the future.
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