152: The Role of Vitamin A in Brain Health

In this episode, Professor Peter McCaffery joins Dr. Buck Joffrey to discuss the multifaceted role of Vitamin A in brain health, particularly its function as a signaling molecule that influences neuroplasticity and cognitive functions.

He elaborates on the challenges of Vitamin A supplementation, especially in aging populations, and the implications of retinoic acid signaling in neurodegenerative diseases like Alzheimer's.

The discussion also touches on the importance of skin health in the context of systemic aging and the potential for targeted therapies to enhance Vitamin A signaling without the risks associated with traditional supplementation.

Learn more about Professor Peter McCaffery:
https://www.abdn.ac.uk/people/peter.mccaffery

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Transcript

Disclaimer: This transcript was generated by AI and may not be 100% accurate. If you notice any errors or corrections, please email us at phil@longevityroadmap.com.

 Welcome everybody. This is Buck Joffrey with Longevity Roadmap. Uh, thank you for joining us today. We are, uh, going to talk today about something else, a little esoteric, I think, um, which is the role of Vitamin A. Its active form is retinoic acid in, um, the aging of the brain. Uh, this is a really interesting conversation with.

It's actually, uh, Peter McCaffrey, who's, uh, in Aberdeen, Scotland. He's one of the leading, um, uh, researchers in this space in the world. And again, you know, I think the idea behind this podcast is not that vitamin, uh, a is some sort of panacea for brain health or anything like that. But, uh, if you're interested in the concepts of, you know.

Uh, brain development, uh, the idea that, um, uh, that senescence is part of the problem with aging and specifically with Alzheimer's disease and other neurodegenerative diseases, I think you'll find this show very interesting. One of the, uh, ideas that I think is, uh, interesting to focus on is something we talk about later in the podcast, which is that as we've discussed before, um, skin health in particular may very well have a significant role in, uh, systemic health and even brain health.

And we'll start to understand that when we talk a little bit about, um, the contagion effect of senescence. And, uh, the role that Vitamin A may play in that. Anyway, very interesting conversation and we'll have that conversation for you right after these messages. Hey, longevity enthusiast. It's time to take it to the next level.

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If you're tired of your belly fat, tired of being tired, or just wanna optimize yourself for the next 50 years, visit longevity roadmap.com. That's longevity roadmap.com. Welcome back to the show, everybody. Today my guest on Longevity Roadmap is Professor Peter McCaffrey. He's a neuroscientist at the University of Aberdeen.

And one of the world's leading authorities on vitamin A signaling in the brain. He earned his PhD in neuroscience from the University of Col, university College London, and has held academic posts in both the US and the uk. Uh, over the past several decades, has research has reshaped our understanding of how retinoic acid, the active form of vitamin A influences brain development, plasticity, and aging.

Thank you so much for being with us. My pleasure. Well, uh, Dr. McCaffrey, why don't we start with this Vitamin A usually thought of as a nutrient, um, but your work shows that it's a powerful signaling, uh, type molecule in the brain. Can you explain that, uh, how it works? Sure. Um, I. That action as a signaling molecule's been known for quite some time, um, certainly since the, the 1980s, so it's been known, I guess since probably the 1930s that Vitamin A was essential for the body, and I'm sure everyone knows that we get it from our, our food, so comes into the body and gets converted in the body, or be actually taken in as a form called retinol.

As the alcohol form of vitamin A, and then it gets transported to any of the cells in the body that need vitamin A and those cells convert, retinol the alcohol to the aldehyde, then to the acid. And the acid is called retinoic acid. And that retinoic acid is, as you say, a signaling molecule. So, although it's a nutrient, it's under complete control being converted to this acid form, this retinoic acid that binds to specific receptors in the cell.

Receptors that are present in the nucleus and that controls gene regulation. So I'm sure your listeners are familiar with this idea that you act on the DNA to generate Mr. A mRNA transcripts, so then get converted to protein and that actually do something. So retinoic acid is the active component of vitamin A to do that signaling that you described.

So your work, uh, a lot of it does, um, involve the idea that the, that there are these receptors in, in the brain and that they may be important for brain health. Um, can you talk a little bit about that? Absolutely. So this has been discoveries just over the last 10, 15, or so years, as I said, venom and A, the idea of the importance of m and a has been around for, you know, a hundred years or more.

Yeah. So it's really only recently that this idea that m and a could be important in the brain. As I say, it is quite a recent consideration, and it's involved in something called plasticity. So it's been known for quite some time that vitamin A is necessary for embryonic development, right? So the developing embryo is controlled by various pathways and vitamin A is really important for that, and it's been known to be important for the development of central nervous system.

So that's the embryo. But there are some events that occur in the adult brain, sort of like what goes on in the embryo. There are changes that go on. Those changes in the brain are what are necessary, for instance, for learning and memory. Now you're talking about n neuroplasticity in that case? Yes. Oh, right, right.

So you, you are well familiar with this idea. So this idea that it used to be a neurosurgeon way, it went done my excellent. Excellent. So, so, so, so the, the concept, uh, so it actually makes, it makes good sense if you're having, you know, if you have, uh, if it's involved in embryonic development. That it would also have this ongoing effect on neuroplasticity.

Correct. Exactly. You've, you've hit the, the nail on the head now. Uh, along that lines too, the hippocampus is especially dependent on retinal gas. Uh, and is that because that's where primarily, uh, that's where the pri uh, primary, uh, neuroplastic activity is occurring? Uh, that's a good question. It's certainly an important, an area where neuroplasticity is important, but there's no doubt that neuroplastic is also important in the cortex.

For instance, in particular the, yeah, the, the prefrontal cortex. You'll be familiar with the fact that hippocampus is involved in, with memory intrinsic to learning and memory. Right. Spatial memory in particular. Whereas cortex and particular frontal cortex is involved in more executive tasks and plasticity is actually important in both.

But Uhhuh, I suppose the hippocampus has probably been. Of all those areas is perhaps understood the best. And so the details of plasticity have, uh, relatively well understood, uh, as understood as best they can, at least in the hippocampus and the roles of. Vitamin A via this signaling molecule. Retinal acid acid are perhaps known the best, so it's involved in the types of plasticity, LTP and LTD, but it's also involved in other aspects of plasticity, things called homeostatic plasticity, and also something called neurogenesis, which you, you may already be aware of, this idea that in certain regions of the brain.

You can grow new neurons. So, you know, I, I certainly learned at school the brain doesn't generate new neurons, but there are particular regions of the brain where that's different and hippocampus is one of them. So new neurons are born constantly and, and vitamin A is probably involved in that. I guess if you pivot then, uh, to the disease implications of this, uh, in Alzheimer's models, uh.

Retinoic acid signaling declines. Is that right? That's the case. Um, we've certainly, we and others have found that, uh, when you look at, you know what, a, you'd be familiar with the disease models that you've got these mice that have, uh, the human mutations for the genes involved in in Alzheimer's, tau. I precursor protein.

And when you generate these models of Alzheimer in mice, then the retinal gastro signaling as the a, as the mice age, the signaling pathways go down. So the implication there is that there's something about the disease results in a decline in the capacity of rettino acid signaling. So may be involved in the disease.

There's, there's. Demonstration of this in the human, I don't think is, is really there. We assume it from animal models. Um, and certainly in humans in general, vitamin A levels are on a decline. So if you take a a, a typical aged person, you are fined. Vitamin a vitamin and a number of other vitamins as well, uh, are not present at the same levels.

There's something to do with the ability of older individuals to be able to absorb vitamins. Perhaps is is one possible reason. Is it? Is, is though that even in the animal models, is it that retinoic acid levels themselves are declining or that the signaling pathways are somehow deteriorating? Yeah, I would say the second, that's what we've certainly found is the signaling pathways themselves is the receptors, for instance, that are going down, but actually also some of the enzymes that are necessary to make the retinoic acid in the first place.

So there though we haven't measured retinoic acid directly. The implication is that the levels of the ligand of the receptor are also going down, but for sure the receptors are going down. Yes. And that's gonna decrease signaling. I bring that up just because I guess the, the idea that then supplementing with retinoic acid may not necessarily solve the problem if it's, uh, an issue of signaling.

You've, you've, that's so unbe nose for multiple reasons. And, and this is the difficulty with probably any of the vitamins. It, it isn't just what you say you are, you are right. The receptors are going down. So if you supplement the vitamin A is not necessarily gonna help, but it's also the body's really good at defending itself.

To get the levels of vitamin A just right. So if you take. I'm sure you and your, uh, uh, listeners are familiar with the idea that if you take excess vitamin C for instance, you just excrete the excess out. Right? Right. And although Vitamin A can't be disposed of as easily as vitamin C, it is still removed and the body defends itself because excess vitamin A can be just as bad as as insufficiency.

So if you try and push the system. Taking say large amounts of a Yeah. Um, it's not going to do a lot necessarily. Um. That simplifying things of course, but it isn't going to necessarily change the levels of vitamin A in your brain very much. And exactly as you said, um, with aging, if the receptors are going down, it's not going to do a lot of good anyway.

Uh, which is painting kind of a pessimistic picture. I don't think it's necessarily quite as pessimistic, but, but neither is it as simple as, oh, we are short of this. We just need to add more of it. Um, and I guess along that lines, there's some a LS research, I think you're involved with. You developed a new, uh, retinoic acid receptor modulator or some modulators.

Uh, so I guess this is, you know, basically trying to help that receptor pathway, not necessarily trying to increase. The amount of re acid. So how, how does, how do they work? How do they help motor neurons survive? Yeah, no, that's a good question. So, um, this is the idea that you apply a high affinity, uh, agonist for the receptor.

So in other words, you are duplicating retinoic acid, but something that binds more tightly to the receptor. So at lower concentration is able to activate the receptor. So it's like a super. Acid or super vitamin A. It's just a very powerful version. It, yeah. So neither is it, it it, it might be considered a bit simplistic in itself.

It is still just trying to push on the system and there's certainly good evidence that for motion neuron disease, a number of the systems that, um, re, that allow retinoic saline to take place are declining. And so the idea is if you try and restore that as best you can with a high potency drug against the receptor, perhaps you can restore some of it.

So, so, so the, yeah. When you say high potency drug, so it's basically just a, a modified vitamin A that is more specific or binds more with greater efficiency to the receptors. Right. So that's, yeah, that in a nutshell, that's absolutely right. It's that version. The act form of vitamin A, in other words, retinoic acid.

So it's an analog of retinoic acid as something that will bind with an even higher affinity to the receptor. Yeah, interesting. So, um, you know, before, before I kind of move on with this, I just did also wanna mention that acid signaling does seem to intersect with inflammation, oxidative stress, and other core processes of aging.

I'm wondering how this all fits together. Yeah. Well, you are too, but what are your thought?

Yeah, me and a lot of other people. Yeah, sure. I mean, this is, this has been something that has been discussed and debated for, for decades now. The, what is the relationship between aging and. All of these neurogenerative diseases, none of which we have good treatments for. Um, and there is no doubt whatsoever that they're related because, uh, the, the strongest factor that leads to neurogenerative diseases age.

Yeah. So it's, it's certainly related to it, but at the same time, there are some very clear differences between neurodegenerative disease and aging because. For the normal aging brain, generally you don't lose neurons. Um, the number of neurons stays approximately the same. As I say, a little bit simplistic, but generally you are not losing neurons.

But if you see some extreme cases of Alzheimer's, when you see the brain, it's just shocking to see. How much the brain has shrunk because of the death of neurons. So in that sense, these are different, these neurogenerative diseases we've just been talking about are, are different from aging. So. There's clearly points of intersection between these and points of, um, differences between them.

There's certainly, of course we do so much with animal models because they can be manipulated to, to such a degree and there's some very good, um, work by, by a number of other groups over in France that in Bordeaux that have shown that. We described earlier how when Neurogenerative disease, vitamin A signaling is going down and with normal aging in animal models, vitamin A signaling is going down.

Learning and memory ability in animal models is going down with age. And when you supplement with vitamin A or or retinoic acid, you reverse that. So from those animal models, there's some strong evidence to suggest. That you can benefit, uh, these animal models of, of aging now equivalent studies and humans just don't exist.

Um, why is that? I, I would think that if I, I, I would think if there was some good data, uh, in these animal models that there, you know, there would be some studies on human aging, normal human aging. Not as extensive as you would assume. I think particularly when for vitamins, there's not necessarily the same amount of money that would, that would be involved.

And I think that that inhibits, but yeah, you, you ask a very good question. Yeah. Yeah. But when you look at the literature, it's really. Very, very little is, is being done. And, and we're not just talking about vitamin A here. It's talking about pretty much any, any treatments out there. Yeah. Um, I'm just curious, maybe there's just not, you know, not enough information out there, but there's certainly hereditary forms of Alzheimer's disease, um, that kind of thing.

I wonder if you see any difference, I mean, even through animal models in. Retinoic acid metabolism in those individuals. Yeah. Um, by definition, the animal models are equivalent to what you describe as those genetic, uh, disorders that need Alzheimer's disease. So, um. That's always been what some might consider to be an issue of Alzheimer's disease research and, and, and all these ones that focus on a genetic model for these diseases such as Alzheimer's disease, as you'll be familiar with, the genetic, uh, cause of the disease is relatively rare compared to the, um, sporadic form.

Um, but that's what everyone focuses on because. A genetic, uh, form of the disease can be absolutely modeled in an animal. So all the animal models that exist are based on those. So I, so when I said that decline in vitamin A signaling, that is what I'm talking about, these genetic models of, uh, of, of the disease.

Okay, got it. Um, kind of moving back into some practical. I guess just for individuals listening, you tend to be focused on health span, you know, I guess in this case, brain span, you know, um, we talked about how vitamin A, it's essential, but can be toxic. So what does that mean for diet or supplementation?

Mm. Is it even, I mean, is it even practical to try or do you just risk. Vitamin Os because vitamin A gets stuck in your, you know, it's, it's, it's, uh, fat soluble and it just kind of lodges into the fat and can give you some kind of other problems. Right? Yeah. Yeah. This is, this is all very true. And making this worse is, is something we published just a, a few years ago, this balance I was talking about, the ability of the body.

To control its levels of, of Vitamin A we, we found just a few years ago. We want to follow up on these discoveries that the brain itself is involved in controlling this balance. So, um, you'll be familiar with how hormones, uh, testosterone, and, you know, estrogen, corticosteroids, they're all controlled by the hypothalamus in the brain.

So this means that these hormones are kept at very precise levels, and we have evidence to say that vitamin A is no different, that literally the hypothalamus in the brain is controlling these levels. So if you're controlling these levels, once again, it means if you take in excess, you have a system that tries to dampen down the system.

And if you have insufficiency, then the system is there to try and boost it up. So when you try and push it in either direction and you know, you are describing, trying to push it in an upward direction, trying to increase that signaling, then you've got this system trying to d in it down, which, which makes it, makes it difficult.

But I guess so how in, in that regard, uh, the idea of creating a. Super Vitamin A, like sort of what you've described, something that's more prolific at binding the receptors might actually, you know, it at certain, maybe lower doses. Just provide a little bit of an advantage if, if the homeostasis in the brain is about the amount of vitamin A.

It's not necessarily, um. If you just give something that's a little bit more potent Yeah. Uh, you, you might have some success. Is that, is that the idea? That that certainly is part of it? A a hundred percent, yes. Uh, you'd be able to circumvent to some, to, you'll be able to circumvent the system I've just been describing.

Um, but the body always has ways to. You know, dampen down everything. So there's, there's no doubt it might find other ways to, to, to, to dampen down even using this as a drug. But I think it, it might be, uh, one way to do this. You, you know, coming back home, I was, I had a feeling you were gonna ask a question, Uhhuh, and I was thinking.

Th this is just a completely off the wall idea. Yeah, we like this. Um, but, um, by chance I've actually just in the last year, I've actually started to teach a course on that includes aging, uh, as it's sort of an introduction to aging. So I have been reading a bit about this and one. Idea I, and I dunno, actually discussed this one already.

Is to do with what's called. Have you have you on your show, have you discussed the idea of senescence? Yeah. As Yes. So you're, you're, yeah. So you are, you'll be familiar with this as one mechanism, probably a, a very important part of, of the aging process. I think it's one that can be understood, one of the better ones, and part of this process of aging.

Um, part of this process of senescence, I should say, involves the release by senescent cells of factors that then damage other cells. Um, and, and this is, is pretty well accepted. So as, as pa part of the reading I was doing for this, this course, there's a, there's a person by the name of, um, Kada, I, I don't know her personally.

She's over in, in Portugal. So she came up with a very interesting idea, whether it's j or not, I, I, I can't say, but a very interesting idea to do with the skin. So you'll be familiar with the fact that, that we don't think perhaps as much about the skin as, as we. Possibly should. It, it makes up about 15% of the body by, by body weight, largest organ in the body.

Sure. Exactly. Exactly. And I suppose it's probably one of the most evident regions where we see changes with aging. Yeah. And retinoid acid is used there all over the place. Right. And it's that I Exactly. I'm, I'm coming around to that actually. Sorry. This, this, this person, this person covered us in, in Portugal.

What she was proposing was that the skin isn't just a sign of aging, but actually might be in some part actually causing aging. So. That as you get senescent cells in, as you say, the largest organ in the body, they're releasing these senescent causing factors. I mean, as the cells become senescent in the skin, they release factors that then cause damage in the rest of the body.

If this word true and I, I dunno how strong the evidence necessary is, it's just a nice idea. Yeah, the skin could be a good target to try and slow aging across throughout the body. So in other words, if you slowed aging in the skin, then perhaps you might have a way to slow aging in the rest of the body.

And that's where what you said comes in that. The evidence is extremely strong that Vitamin A and retinol does actually have positive effects on the skin in terms of slowing aging. The, the, the molecular evidence is extremely good. It restores collagen in the skin. Um, it has actions on, um, the, the, uh.

Vasculature in the skin, it, it improves that it's acting on multiple factors. Oh, it's actually also acting on the stem cells in, in the, in the skin in a positive way. So, although I was doubtful, you know, I could see it is difficult. Perhaps there'll be ways in the future, but it's difficult to say change the vitamin A levels throughout the body.

But it probably would be. You could raise vitamin A levels in the skin and possibly do it more safely as well. Because, you know, if you are, if you're adding too much vitamin A to the skin, you see it immediately. You know, you, you see skin will start to flake if you, um, if you see that. So you can immediately stop if you're adding too much.

So I was thinking, well, there's an interesting idea if we're able to find funding. Yeah, I think it's very interesting concept. Actually. There's a company, um, that, uh, I interviewed the founder of, it was called, uh, the, the company's One Skin. I don't know if you've heard of that. No, no, no. But they, they have, I don't remember what's the compound, but it, it is a, it is, um, it, it is been studied pretty well for, um, eliminating senescent cells.

Um, they've, they've turned it into a, a, you know, moisturizer they sell, but it's a, um, but her whole entire concept was this, is that skin health is actually systemic health. Mm-hmm. Because again, the concept of senescence essentially being in some ways contagious to other organ systems. Right. The idea that, you know, you've got, you know, whatever.

Toxic cytokines or whatever that are being released mm-hmm. Into the system from the largest organ in the body. Makes a lot of sense. If you can reduce that, that you would reduce potential. I guess using the word contagious kind of makes sense in this regard, right? Mm. But other, other parts, no, it fits in with exactly that idea I was, I was describing before.

Exactly. So what was the compound then that they were proposing? I wish I could remember, but it's, um, but the com, it's one skin. I actually started use myself. Um, it, but it is, um, uh, it's something that they were using. They use machine learning to figure out these compounds to, you know, isolate them. Yeah.

But it was, it wasn't, um, it wasn't retinoic acid. No, no. Yeah, no. Definitely wasn't retinoic acid. No. And you know, probably in part, you know, as to your point, retinoic acid is great, but it, it also, if you use it. A little bit too much. You, you create some pretty significant side effects on the skin as well, so you, you absolutely do.

But, but because it's on the out, obviously off the out surface, you can actually see that, uh, damage being done. Whereas if you're taking it orally, then the damage that can happen, for instance, particularly in the liver, um, you're not immediately aware of, um, right. So I just looked up this active compound in one skin, and it is, um, it's called the OS one Peptide.

And it's, uh, basically they, they screened over 900 peptides for, uh, Eno Therapeutic Potential. And they found this one to be, uh, the most, uh, the most effective in that regard. Um, yeah, so it's, it's just like a peptide formulation, but interesting concept definitely to apply to this. Yeah, it is, it is. I I just, just to jump in.

Yeah. One of the advantages with something like vitamin A and and retinoic cancer acid, it's quite a lipophilic compound, um, uh, is, it's a small lipophyllic compound, so it actually penetrates tissues quite well. And when you have things like. Proteins or even peptides, um, they don't penetrate, um, tissues as as well.

I'm sure you can perhaps design the peptides, add, you know, certain compounds to them that, that aid that penetration, but you've got an advantage there with vitamin a retina, I guess that it gets into tissues easier. Um, going back to the compounds that you've been developing, um, are these things that you, um.

Are commercially available. Uh, the sort of, the, the, the better, uh, you know, these more, uh, super vitamin A compounds. Um, right. So are they, so these, yeah. Mm-hmm. So, so these have been developed by, um, Andy Whiting and, and his group. Um, em, Kapo as well. Uh, uh, Durham and Andy Whiting started this company, ne Genix.

So at this point, um, they're not commercially available. Um, but he's certainly distributing, distributing these to, to many different researchers, to, to test them out because he's, for various good reasons, very hopeful that they are going to be, uh, useful for. Neuro degenerative disease because of their Yeah.

Sort of pro survival, anti, you know, apoptotic, um, anti-inflammatory actions. They, they do seem to act in, in multiple ways, and I suppose that's an advantage with this vitamin, a retina acid signaling system. It turns on a lot of different factors. It's not. As for instance, uh, you know, obviously one of the, uh, best known recent treatments for Alzheimer's disease is antibodies that, um.

Basically target, uh, B amyloid. So that's targeting one very specific cause of the disease, whereas retinal acid is acting on multiple elements of the disease. So the hope there is that if you are acting on multiple different components, you are going to have a greater effect on the disease that clearly is consists of multiple.

You know, uh, changes that are going on in neurons that lead to, uh, cell death. So for instance, there's an anti-inflammatory action of retina acid. So inflammation is considered to be a, uh, probably one of the key, one of the several key components that lead to death of neurons in the disease. So if you can have something that's anti-inflammatory.

Um, is, uh, antioxidant. I, I think you, you, you mentioned earlier. Mm-hmm. Uh, this is a pathway that leads to, to death, that you have this oxidative stress and rettino acid and vitamin A also seem to have, uh, uh, an action to reduces oxidative stress. Is there, I'm just curious, um, are there diseases. Of poor vitamin A metabolism.

Yes. There, there are, um, not so many of them that are specific. So there's some genetic disorders, for instance, to, to give extreme examples. There's a genetic disorder that, um, is a mutation in the. Protein that transports vitamin A or retinol into the cell. So when that becomes mutated there, um, the effects on people is, is extremely severe.

Um, so it resorts in developmental abnormalities. And cannot lead to death in the first few years of, is it, are, are some of the, uh, I implications or is some of the sequela severe brain related issues? They, yeah, very much so. Yeah. But they're, they are developmental, I'd say for the most part. So in other words, because you're interfering with reaction of vitamin A on the developing embryo, um, this, this leads to all these, these birth defects.

There are some other, for instance. You'll be familiar with the fact that one way you obtain vitamin A is to be the ene. Um, so that's obtaining it as a molecule that's sort of like two, uh, molecules of, of vitamin A sort of joined covalently together. And there's an enzyme, uh, an oxygenase that breaks that.

And so you can then generate vitamin A from that, but you absolutely have to have that enzyme to, to break. That, the bond between those two, and there are people who have a, a weaker form of that enzyme, so they won't be able to use beta carotene as well. So for instance, you know, everyone knows that carrots are a great source of visin A, but they're a source through betacarotene.

Great. So if you're not as good as, uh, being able to use betacarotene. You could be more likely to be, uh, susceptible to, you know, not necessarily absolute vitamin A deficiency, but, but some level, I mean, vitamin A deficiency of course is, is, is common in the world it, but in. You know, we're talking about, uh, low income countries.

I mean, it's endemic in the world. There are millions of children who are, who are vitamin A deficient. It's just that now that they're not people we come across that the people in far away countries who, who are, who are suffering from this. Um, to what extent is Vitamin A deficiency a problem in, in the, in, in our worlds, to a much less lesser extent, but.

It seems likely there will be people, um, with these mu genetic mutations that mean they're not able to metabolize, for instance, be the carotene as well, or their diet isn't necessarily an ideal one. So, although vitamin A is not like vitamin D, I mean, I think vitamin D deficiency is. Relatively common.

Mm-hmm. Especially in a place like Aberdeen where we, we don't get so much sun during the winter. Sure. Um, so vitamin A's, not like vitamin D, but I, I think there will be some people who will, through genetic causes, have some problems with, uh, with, uh, bit amazingly, but is there's just not enough understood about it to be able to screen for those people.

Yeah. And even make the judgment how many it might involve. Sure. Well, you know, as a takeaway, I guess, you know, for our listeners, if there's one thing that you should take away about vitamin A signaling and longevity and any sort of words of wisdom, what would it be? Well, I would come back, I suppose, to this idea of the skin.

And as I say, it's an idea that I reckon only recently, you know, only, I was just thinking about just coming home tonight. That might be a way, that might be a way because I, because although of course you can say, you know, we should all be getting our, our, our, our vitamins and they're an essential part of the diet.

Of course that's com all will always be true. But everyone knows this already, I suppose. Um, and as I said earlier, it's hard to push on the system if you. Had reasons to believe you were vitamin deficient. It's hard to push on the system now for the very elderly. It, it might be true that you'd be vitamin A deficient because as I, as I say, the, the, the, the, the pathways involved in, in absorption of, of vitamin A and, and multiple other nutrients declines with age.

So. With the elderly, you would, uh, consider the possibility that you could be more likely to be vitamin A deficient so that you should be taking vitamin A tablets. That, that you should be taking a multivitamin if you thought you were Vitamin A deficient is a good idea. But none, none of, I think every, all your audience would probably be aware of this already.

So that's why I think this idea of skin health. Is is one that, that might be, um, useful because it's, as I say, it's more difficult you to overdo things because if you, if you're applying too much for seminated your skin, you'll see it immediately. So you would immediately know, I have to stop. Yep. Um, and maintaining good health of the skin and slowing the aging process in the skin might not just be useful for, you know, visual appearance, but may actually be good for the body as a whole for the reasons you were just describing.

Interesting stuff. Um, where can we learn more about your work? Um, you could just, well, I would encourage anybody to email me. I, I, of course, always enjoy answering questions by, by email. Um, so, uh, there's a University of Aberdeen webpage that, that. You should be able to easily find by just looking at my name and University of Aberdeen, so you can just look at the websites and there's certainly information on some of the research we're doing and the papers we published, or please just email me.

Thank you so much for being on the show today, Dr. McCaffrey. It's been pleasure. Yeah. Lovely, lovely chatting with you, buck. Have a great day. Thanks for listening. A quick reminder that while I am in fact a surgeon, nothing I say should be construed as medical advice. Now, make sure to include your physician in any medical decisions you make, and also, if you're enjoying the show, please make sure to show your support with the like, share, or subscribe.