COSMOFACTORY

Deanna: [00:00:00] This episode is about dermatology and longevity. It's about NAD plus. The oxidized form of a nicotinamide, adenine, dinucleotide molecule. It's about skincare, about supplements, and it's about the science of optimal skin cell function. Today on the Cosmo Factory Podcast, I am speaking with Dr. Anna Man Nova, associate professor in dermatology at Harvard Medical School, and co-founder of New Frontier [00:01:00] Bio.
Anna, welcome to Cosmo Factory.
Anna: Thank you for having me.
Deanna: No, you're welcome. I'm delighted for the chance to talk with you beside the credentials I mentioned just a moment ago. You are also director of the Harvard Stem Cell Institute Cutaneous Biology Program, and associate director of the Cutaneous Biology Research Center at Massachusetts General Hospital. I want to start our conversation well before all of that was true.
Will you tell us what was happening in your life when skin first started to matter to you?
Anna: Sure. That's actually a great question. So, um, I finished medical school in, uh, so Bulgaria and I went to, um, the University of Basel in Switzerland to continue my training in the MD PhD program of the University of Basel, where I actually got, uh, excited by portion of biology, [00:02:00] which, um. Studies, um, the deep structures within, um, the cells of our body.
It's called structural biology. And while I was, um, working on my PhD project, which was actually on heart development, um, I started to wonder how, um. Tough structures in our bodies are flu and one of the toughest is actually the skin. And that's what, uh, united my interest in skin biology. Um, and I moved to the United States to continue my training and.
It happened just by chance that an opportunity opened for training in, um, ski biology. That's how it all started. Um, that was about 25 years ago. I came to the US to do two, three years of training, uh, stayed here and, um, developed my interest in skin biology. I started my [00:03:00] laboratory working on skin about.
15 years ago, and my interests are really focused on how our largest organ, the skin works and how it executes one of the most important functions in our body, protection from the environment. Um, and that's how it all started.
Deanna: That's fantastic. I, I appreciate you sharing that with us. We are getting into a conversation today about longevity. So for context, I have some notes to share with listeners. It was, um, around 2022, I would say, when the cosmetics and personal care industry began talking freely about preventative skincare and this idea of longevity.
Now, certainly there was work going on before that, but this concept. Began to surface really quite recently, um, around that time. Ingredient makers, formulation laboratories, multinational brand leaders, startups for sure were sharing data and launching products, highlighting serin as well as [00:04:00] NAD plus, and their connection to skin longevity, I think in particular about companies like Estee Lauder or MI Biochemistry here.
Now, still today in 2025, serin and NAD plus stand out in the marketplace as leading edge skincare science. And they are in fact what led me to discover your work. Anna, I wanna shortcut some of the science here. Uh, we are talking about optimizing skin biology. Your specialty as, as you've just shared with us, and active serin are a prerequisite.
So humans have about seven serin. Serin happen to be both enzymes and proteins. Um, and some enzymes require, um, a co-enzyme in order to function. Uh, serin, uh, that is true for serin, NAD plus is their co-enzyme. There are of course, a number of other factors that support serin function, but as I said, we need active serin for optimal skin activity.
And this optimal skin activity equates, uh, at least in my mind and I, from the science I've heard [00:05:00] to skin longevity. So, uh. Uh, a question for you, Anna, when, when you and I met earlier this year, it was a Zoom call, but you explained to me at that time that as we age, we actually have fewer layers of living skin than we did in our childhood or teen years.
Can you talk about this phenomenon and then how it relates to optimal skin function?
Anna: Absolutely. Um. So the skin generally is composed, um, of, uh, few major layers, two of which are the most important. The lower layer, we call it the dermis, which serves as a scaffold. Um, it actually holds the upper layer, which is the barrier, and it's called the epidermis. And the epidermis is the subject of our studies in that.
Past 15 years. And the reason for that is that it really serves a key function for our survival. It protects us from toxins, from pollutions in the [00:06:00] environment, from the sunlight, from, um. Various insults and it protects our entire body. It also talks to the body. It translates signals from outside to every system in the body, starting from the immune system to the brain.
So it has a really a key function and because of that, it needs to be held, um, intact. Dermis itself is composed of several layers of cells. These cells will start from, um, the stem cells, which are at the bottom of dermis and what they do, um. Through the life of the human, they actually, uh, commit to a process which we co differentiation, which means that they, um, generate their progeny, which then adopt the function of creating the barrier.
And when the stem cells do that, [00:07:00] uh, lying at the bottom of the epidermis, they start to push this differentiating progeny upwards. And each one of these newly. Formed cell types creates a layer at the top of, uh, these layers. These are usually seven, eight layers. And, and the last two, three layers are actually dead cells.
So the function of the, uh, epidermal stem cells is to commit suicide. The most useful suicide, um, a cell can do. Um. To sacrifice self, to protect our body because the dead cells on the top of the epidermis form, um, a structure, we call it an armor. It really is, um, um, barrier, which protects us from everything.
So this process of, um. Committing to differentiation, forming the structures we call [00:08:00] epidermal hemostasis. A very important part of this process is the replenishment of these dead cells, which are being decimated with millions every day of our lives. So we have a process where the basal cells, um. Commit to differentiation, ellish the barrier, and ensure that the skin does its job of, uh, protecting the body. This, um, entire, uh, processes, as I mentioned, essential for our survival and it has to ca be kept, um, in at bay through our life. I can tell that every person gets a brand new epidermis. Every four years of the adult life, this is an enormous amount of work, which is, um, these stem cells do, um, and a very essential amount of work.
And, um, I would like to add a little bit to the [00:09:00] story you told about, um. Nucleotide, as we call it, NAD and serin, NAD. It's very important, as you mentioned, for the function of the serin. The serin are key for cellular function in the skin, but NAD has also another function. It ensures that the entire metabolism in.
The cells, and particularly in the epidermal stem cells, is intact. And this is important because leads to the production of one key ingredient for our skin health. It's energy, it's a TP, which provides energy. Energy. Without energy, the skin stem cells cannot, um, produce energy and cannot. Undergo this very complicated, very energy consuming process of differentiation. what really excited us years ago is to learn [00:10:00] that as we age, the skin stem cells actually stay more or less the same. Our hypothesis was that they get less then they age in a way. But we couldn't really determine, or we couldn't really pinpoint that. Something is very wrong with that. The numbers were the same.
Um, the, the appearance of these stem cells was the same. So we were wondering what happens actually during caging. And here comes the story of, of NAD. Um, my laboratory discovered fairly recently that, um. The production of energy of a TP, which is driven by the, um, um, ability of cell to, um, produce a, um, is key for, uh, the differentiation process to occur.
And [00:11:00] this discovery made, made us think that, um, during caging. The fact that the levels of NAD are going down, which is a well known path, likely means that the ability of our stem cells to produce energy also diminish. So we ask the question, what happens when there is less energy produced by stem cells?
And we were able to show that. When there is less energy, the differentiation process still happens and happens very well, but it's just weaker. And now, instead of being cable to, um, produce the entire cascade of differentiating cells, which I set are about seven day layers, we produce less. And this leads to the hallmark.
Of skin aging, which is the thinning of our upper layer. Uh, the skin epidermis, the thinning of epidermis, [00:12:00] um, is what gives the older appearance of the skin, but it also means something very important. Thinner barrier means less barrier function. Our skin becomes, um, a bit more, uh, a bit less protected or, um, I would say.
It protects less our body. Um, it starts to let toxins in, inflammation grows. Um. Not only appearance suffers, but also function suffers. Um, we start to develop more inflammatory diseases, the crosstalk with other systems such as the brain is suffering. Um, and there is a whole other things going on which are actually originating in aging skin.
So discovering that made a sting that, um, NAD ski in, um. Keeping the skin, um, doing its job, um, [00:13:00] developing a barrier. So we, um, performed experiments showing that supplying NAD, um, to skin stem cells, um, helps them execute, um, the full differentiation program e even if they're aged. Um, and that's how the idea about, um, supplementing Kennedy to skin stem cells, uh, came.
Deanna: Yeah. And, and let's talk about that. Let's talk about both sort of topical, um, products as well as, as maybe, um, ingestible supplements. Let's think about topical skincare first. How can a topical product play a role in this skin longevity process that you've described?
Anna: Absolutely. So, um, as you mentioned at the beginning of the podcast, um. And I would like to mention again here for disclosure, I'm a co-founder of New Frontier Bio, which develops products, um, related to the [00:14:00] work I do. Um, so, um, back to your question, how topical skincare can actually, um, uh, if you, if you wish, uh, utilize these findings.
Um, topical skincare is a. Um, very interesting, uh, topic to me. Um, there is a huge variety, as you know, of skincare. Um, skincare generally has two major problems, um, which are very, very, uh, true today. Um, problem number one is that we tend to overload skincare with a lot of ingredients for many of which we don't really know the function.
Um, and that leads to problem number two. Um, and, and problem number two is not only true for skincare, it's true also for every topical treatment we apply to the skin for [00:15:00] cosmetic or therapeutic, um, reasons. As I mentioned, the who, biology of the skin has one goal perform this barrier so naturally. Um, there is no easy way to break the barrier and luckily there is no easy way to break the barrier.
So many of the skincare products suffer from staying on the surface without being able to actually penetrate. And, um, what I like to tell, um, my students, for instance. Is that when they use skincare and they see an immediate effect, like you get the newest skincare product, you apply it, and the next day you see a different appearance of your skin.
This only tells you one thing that the biology wasn't really affected. Because biology takes time. This whole differentiation process, this whole, [00:16:00] um, common static renewal of the skin, as I mentioned, is four to six weeks. So for, for a consumer to really see an effect, it takes that long. What we actually see, something which is also very important for the biology of the skin, but it has also an optical effect, and this is hydration.
And when we hydrate the top of the skin, these dead cells expand and cover some imperfections. Give the appearance for a more, uh, the, the, the impression for a more plumb appearance. And that actually is the effect in the mirror. This doesn't really mean. That, that you affected biology? Um, so, um, back to the problems of skincare, right?
Ingredients and penetration. Um, and, and they're connected because when you overload the skincare product with many ingredients, you, [00:17:00] um, also, um, make it more difficult for those ingredients to go deeper. As I mentioned, the stem cells in the epidermis lie at the bottom of epidermis. Below them is the scaffold, the dermis.
These are the two. Of the skin you wanna treat the stem cells and thees, getting there is really, really hard. We haven't completely solved that problem. There are a lot of advances in bioengineering, which are, uh, utilizing, uh, different formulation techniques to penetrate. Um, so that's something to keep in mind.
Um, and second is. I use less ingredients, which are powerful and from what our work has shown, and it is one of the most important. Um, our work has also shown that, um, as we all know, energy [00:18:00] production and meta metabolism requires fuel or food. Um, we utilize generally three types of food, fat, sugar, and proteins, and most of our cells use all of them together.
Our work has shown that, um, epidermal stem cells rely exclusively on fat or lipids to actually. Execute the, the, uh, program. They're designed to do the differentiation program. So the combination of an ad and lipids is something we know as benefits for epidermal stem cells, and that's what, um, we think, um, would support a healthier.
Deanna: Can you differentiate just briefly, we're very short on time here, but can you differentiate, um, the difference between a lipid ingredient that has benefits and a, a topical ceramide?[00:19:00]
Anna: Sure. Um, sure. Um, they're both similar in class. Uh, topical ceramides are important because they're part of these very, uh, top layers of epidermis where the dead cells are starting to form their armor. Um, they're important, uh, components of this. That's why we supplement that. Um. Lipids or, or fatty acids component.
The co, the basic components of lipids. The building box of lipids are the few, the food that epidermal stem cells, which are at the bottom of the epidermis, utilized to produce energy. So both are important of different functions, um, but extremely key for.
Deanna: Okay. No, that's super helpful. And I, I do wanna talk about nutricosmetics as well, the ingestible supplements. We know from looking at the marketplace. This is, um, a phenomenon, if you will, or, or a product class that's definitely here to stay. Uh, is there an. A genuine place [00:20:00] for Nutricosmetics in the skin longevity conversation.
Anna: Absolutely. I, I do think so. And the reason I'm convinced this is the case is as, as, as I mentioned, um, formulation with Ensure complete penetration of topical skincare are very hard. Um, I'm convinced if. Everything we know about the skin is true. It's gonna be really, really hard to completely penetrate the skin unless we use interventions such as needles or lasers, uh, or other devices.
The alternative is to supply these ingredients, uh, from the bottom. And the only one way to do that is through the circulation by taking ingestible supplements. The question of course, would be how much we need to take to get to the right concentration, and that's a matter of, um, studies and clinical trials.
But that's where I see, um, to have an [00:21:00] impact.
Deanna: And I wanna think a little bit about supplements insofar as I, I know there's concern about the fact that they sort of go through our digestive process, right? When we hear about collagen supplements, there's a, a whole school of, uh, formulators and scientists who are saying, like, these supplements break down into their constituent peptides.
Your body then decides what to do with these peptides. They may or may not. Reconfigured to become collagen, you know? So how valuable is this supplement, if it's a, you know, if it's a, a finished collagen, is the same true with NAD plus? Do we need to feed ourselves that or are there other bits? And then how do we know they're affecting the skin?
Can you comment on that sort of conundrum?
Anna: Absolutely. Uh, great question and, and there. A lot of studies done, a lot of studies ongoing, which are asking exactly the same question, so I don't think the exact answer is out there yet. From what I can tell you from, from our work is that, um, we do [00:22:00] believe that, um, supplying, um. The cell with, um, precursor affinity is the better choice than supplying it directly with NAD.
Um, simply because we give the cell then the choice to make as much as it needs. Um, and choosing a precursor, we choose a approach which is a bit easier to be modulated for supplements. So these two, um. Advantages of, of, of choosing a precursor, I think is something which we have to consider when we make supplements in our, um, work in the laboratory.
We've, um, executed all our experiments only with, uh, precursor affinity simply because we wanted to really, um. Give, as I mentioned, the cell, the choice to make as much as it [00:23:00] needs. Our work is done with liquid nucleotide or nmn. There are other precursors, but, um, all our studies were done with this particular one simply because, um, our research, uh, in terms of literature show that this is likely the best way to supply skins stem cells.
Deanna: And I'm just curious, are you able to actually then measure how much NAD plus the body does make? So are you looking really at sort of functional results? Mm-hmm.
Anna: Uh, both we've done, um, work to measure NAD levels in the skin after supplying NMN. Um, to me the, the, the most important, um. Um, marker biomarker, if you wish, is to, to measure the ability of the stem cells to, um, commit to differentiation and renew in a healthy way. And that's been our golden standard [00:24:00] for, um, um, biomarker for, um, sufficient levels, affinity and proper epidermal stem cell function.
Deanna: Perfect. Perfect. Uh, for folks listening who might have a particular interest in longevity. Before we finish up, I wanna point out some previous Cosmo factory episodes that do cover this topic. Episode 25 is called Skincare Reimagined and episode 59 called Skincare and Longevity. Uh, as it sounds, those would be interesting for you to listen to.
Also, episode 45. Optimizing beauty care for every generation does touch on this concept of longevity as well. And Anna, now you have so very intelligently and kindly enriched our perspective on skin longevity science. I appreciate your taking time to speak with me today. I thank you for being a guest on the Cosmo Factory Podcast.
Anna: That's been very exciting for me too. Uh, thank you very much for having
[00:25:00]