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Kris Verburgh on NOVOS at EARD2021

This talk focuses on NOVOS' science-based approach to choosing its ingredients.

Kris VerburghKris Verburgh
 

At Ending Age-Related Diseases 2021, Kris Verburgh of NOVOS explained what goes into NOVOS nutraceuticals and his company’s philosophy towards their development.

Script

Hello, ladies and gentlemen, my name is Kris Verburgh. I’m a medical doctor, scientist, and co-founder of NOVOS. NOVOS is a company that provides solutions to live longer, healthier lives. During this brief presentation, I would be happy to quickly introduce NOVOS to you and to explain some problems we want to solve, and during the second part of this presentation, to go into depth regarding the science behind some very interesting ingredients to slow down aging.

Let me first start with NOVOS. The vision of NOVOS is to extend humanity’s healthspan and lifespan, and our mission is to become the go-to source, the trusted source, for scientifically superior nutraceuticals, tests, and education to mitigate and slow down the aging process. And in fact, we want to address three main problems, problems that a lot of people experience.

The first problem is that most anti-aging supplements have little or no science behind them. If you want to find a supplement to slow down aging, you have a lot of choices, but unfortunately, most of these supplements are not based on real science, or are based on outdated ideas about aging, for example, that anti-aging supplements should contain antioxidants. Most antioxidants don’t slow down aging; some of them can even accelerate aging, and this is one of the many misconceptions about anti-aging supplements. The problem in general is that it’s just very difficult to find science-based anti-aging supplements or nutraceuticals.

A second problem a lot of people encounter is that there are so little good tests to assess your aging process. If you want to have an idea of how old you really are, biologically speaking, or track your aging rate, or to assess your general health and mortality risk, it’s just very difficult to do so. You can go to your medical doctor, and that person will measure your blood pressure, will do some rudimentary tests, including a blood test. Most blood tests are normal, but still you can eat, fast, or be deficient, and so on. So it’s just very difficult to have done good tests to assess your health and aging process.

The third problem is that there is a lot of misinformation about aging, like we just discussed. The idea that antioxidants slow down aging is a big oversimplification and misconception. There are many other, let’s say, misconceptions about the aging process and how to slow down aging and about what to do to live longer, for example, diet, so you have hundreds of different diets you can try. But, as we also briefly will discuss, most diets are not that healthy in the long term. In the short term, you have health benefits, but in the long term, most diets can even accelerate aging. Anyway, it’s very difficult to find good information, and that’s also a problem we want to mitigate. We want to provide solutions to these very prevalent problems. We want to be the one stop for longevity.

First problem, of the lack of science-based anti-aging supplements; we want to address that by creating nutraceuticals that really have good science behind them regarding targeting aging and slowing down aging. We created two supplements or nutraceuticals, NOVOS Core and NOVOS Boost, as an answer to that. We will also offer third-party longevity tests that are that can really enable people to better track their aging and health. And knowledge, we want to really disseminate knowledge to help people to live longer, healthier lifespans.

Regarding the nutraceuticals, we have created a foundational product, it’s called NOVOS Core. It has been launched quite recently in January. It contains 30 sachets; it’s a powder containing 12 science-based ingredients. Each ingredient has scientific studies shown to extend lifespan in various organisms or be associated with reduced mortality in humans or has shown to act on specific hallmarks of aging. We created a powder that we put into sachets because all of these ingredients, the doses are quite high. You need to take one or two grams per day, and you cannot put that in a supplement.

That’s also another problem with a lot of anti-aging supplements. The doses they contain are way too low to really have physiological effects or to make a dent in the aging process. If you really want to do this well, you need higher doses, and you can only do that by putting it into a sachet.

We also offer NMN. NMN is a very well-known anti-aging supplement, very popular. The problem, however, is that if you go online, it’s very difficult to find high-purity, high-quality NMN. Despite some sites saying they’re high purity or high quality, the NMN is adulterated, or it’s low quality, or the purity is not absolute purity that is comparable to all the supplements out there. There are a lot of problems with finding good-quality, high-purity NMN, and we want to provide that kind of NMN to our customers

The second aspect of this nutraceutical, besides that it’s science based and uses high-enough doses, is that it’s the first nutraceutical specifically designed to target the root causes of aging. In the last ten years, we discovered more about aging than the last thousand years, so that’s great. We have discovered that aging is much more complex than just being caused by oxidative damage.

A lot of nutraceuticals, they focus on one aging hallmark or aging mechanism, like oxidative damage or mitochondrial dysfunction. But there are many other reasons why we age, and we specifically created NOVOS based on the idea that there are multiple causes of aging, at least nine that we want to address with our nutraceutical.

It’s not just oxidative damage or mitochondrial dysfunction, it’s epigenetic dysregulation, also proteostasis, which means accumulation of proteins inside and outside of cells that contributes to aging, stem cell exhaustion, telomere shortening, altered intercellular communication, epigenetic changes, and so on. Most other supplements are based on just one simple idea or mechanism of aging, but we want to really expand on all these multiple aging mechanisms.

Besides specific nutraceuticals, we also want to offer tests to assess your health and aging status. There are two kinds of age: your chronological age and biological age. The chronological age is the age on your passport, it’s how old you are in years counted as revolutions around the sun. But there is also something like biological age, it’s how old you really are.

For example, you can be 50 years old, but if you live unhealthy, you eat not very well, you don’t take a lot of supplements or you’re deficient in all kinds of nutrients, and you don’t exercise and are under a lot of stress. You are chronologically 50 years old, but biologically, you’re 58 years old. If you’re biologically older than your chronological age, that means you have an increased risk of dying and an increased risk of getting all kinds of aging-related diseases.

We want to offer tests to better assess your biological age. Currently, we offer two free tests, we will further expand, but one of the two tests we already offer on our website is a comprehensive health questionnaire that asks you more than 30 questions regarding your health, and at the end you have a health score, so you can better assess and see what to pay attention to regarding your health.

We also offer facial AI tests. That’s a test that you just upload a selfie from your smartphone or from your computer, and then your selfie image will be analyzed by an AI that has been trained on more than 12 million images, and you will get a score.

The AI will give you the facial age score and also individual scores for eye bags, wrinkles, skin uniformity, skin redness, and so on, and you will also get a lot of advice to improve each of these specific face biomarkers. But we will offer much more tests, so please stay tuned, and this is just a beginning.

A third aspect of NOVOS besides offering tests and neutraceuticals, is to disseminate knowledge, we really want to help people to live longer, healthier lives and to share knowledge on how to achieve that. We are also a public benefit corporation, which means we want to benefit a large audience by educating the general public and also by funding aging research. A part of our profits goes to funding fundamental aging research to further advance the field.

This is an example of information we share on our website, these longevity diets. There are a lot of diets out there, hundreds of different diets to choose from. All of these diets, they work in the short term, they enable weight loss or they achieve improved insulin sensitivity or they lower your cholesterol. But in the long term, often these diets are not that healthy and can actually accelerate aging.

So we explain this on our website, and we also offer our own model, a longevity diet disc, and you can just print it out and put it on your refrigerator, to inspire you to eat healthier or to help you in your food choices.

We also are quite unique as a company in the sense that we have a great scientific advisory board. We have wonderful scientists that are advising us, including George Church from Harvard University. He is one of our scientific advisors, and he is on our advisory board. He is an authority in biotechnology, he has advanced the field through great innovations, and he has also done very interesting research into aging like extending lifespan in animals by combining multiple genes together and so on or changing multiple genes at the same time. So he’s a real legend in biotech and aging.

We also have Joao Pedro de Magalhaes on our Scientific Advisory Board. He’s also a very well known aging researcher. We have Dr. Rosenbaum, Dr. Mark Kaeberlein, Dr. Pamela Maher, who is an authority on flavonoids and neurodegenerative diseases like Alzheimer’s disease. We have also Dr. Medvedik. So we have a great team of top scientists that helped us with the formulation and advise us, and that helps us to aspire to to be a very science-based company that really wants to make a dent in the aging process.

That leads us to the second part of this short presentation, it’s a more scientific deep dive into some of our longevity ingredients, and I will be happy to discuss the science behind some of of the ingredients we use.

The first ingredient that we picked is alpha ketoglutarate, or alpha ketogluteric acid. AKG, or alpha ketoglutarate, is a very interesting substance. It’s a substance that occurs naturally in our body. When we get older, the amount of AKG declines.

It has shown to extend lifespan in multiple different organisms. Also. in mice, besides extending lifespan, it has shown to reduce hair graying and reduce baldness in some mice too, which is not that surprising if you look at how AKG works. AKG can impact multiple aging hallmarks.

It can improve the epigenome. Alphaketogluteric acid is a very important substrate of pivotal enzymes that play a role in epigenetic reprogramming. AKG is a substrate for the Tet enzymes that stem from ten-eleven translocations, and these are important enzymes that maintain the epigenome. Interestingly, alpha ketoglutarate works together with vitamin C to impact or improve the function of the TET enzymes and other epigenetic proteins in ourselves.

AKG also is an important substrate in our mitochondria, so it’s a mitochondrial fuel. It’s part of the Krebs cycle, the Krebs cycle is the cycle of life. It converts the food we eat into energy that we need to make everything run in ourselves. AKG is an important subset of this Krebs cycle.

That also explains why, for example, athletes or people that have to really do a lot of endurance exercise, they take AKG to improve stamina and endurance. Also EKG, there’s a lot of signs that it can improve stem cell health, through epigenetic effects and other effects. It’s also involved in collagen synthesis.

That’s why it’s perhaps not surprising that AKG improved skin in mice, for example, and reduced hair greying because of these effects on the skin, stem cells, among others. You can see some examples of studies that show that AKG can extend lifespan. For example, in the middle, you’ll see a graph in which little worms called C. elegans exposed to AKG live longer. On this other graph on mice, AKG will extend lifespan of these mice but also improve their health.

Another interesting ingredient is fisetin. Fisetin is a substance that occurs in nature in strawberries, for example, but in much lower levels. You give it in higher levels, or higher amounts, it has shown to have senolytic activity, which means it can kill off senescent cells. But it’s very interesting because a lot of senescent cells arise when we age. So senescent cells are also called zombie cells.

They occur, for example, in the skin, but everywhere in our body, the cells refuse to die, but you’re damaged by aging processes, and they secrete all kinds of substances that damage the healthy surrounding cells.

So they secrete matrix metalloproteinases, for example, or pro-inflammatory cytokines, that damage the healthy surrounding tissues. So if you have a lot of senescent cells in your skin, that contributes to skin wrinkling, senescent cells in the blood vessel walls, contributes to atherosclerosis, certain cells in the liver to liver malfunction and metabolic dysfunction, and so on.

Fisetin could clear away these senescent cells, but it also has many other effects. It can reduce inflammation in the body, it has epigenetic effects, it can improve metabolism and so on. As you can see, in the middle, you’ll see a graphic study about mice that received fisetin, and their healthspan and lifespan was improved.

Lithium is also a very interesting substance. Lithium is a mineral; it’s often found even in drinking water, it seeps out of rocks into drinking water, for example. Lithium is shown to extend lifespan in multiple organisms, different species, and also to reduce neurodegenerative diseases in multiple experiments.

In humans, there have been done clinical trials where lithium has shown to reduce the progress of Alzheimer’s disease. It’s very important to take it long enough. For short term studies, you don’t really see an effect, which is quite logical, if you just give it for a few weeks, it’s not going to mitigate a disease that often takes decades to develop like Alzheimer’s disease, but if you give it long enough, we’ve seen in clinical trials in humans that it can mitigate the progress of these diseases.

There are also studies that show that in regions where the result of lithium in the drinking water, there is less Alzheimer’s disease or neurodegenerative diseases. There’s also less suicides, and people tend to live longer. Of course, it’s just this association, not a causal connection. But still, through experiments in animals and clinical trials in humans, we see there is a strong causative effect of lithium on brain health especially, but aging in general.

Mind that we are talking about microdosed lithium in this context. Lithium is also used in clinical settings, in psychiatric settings, as a as a drug to treat bipolar diseases, because in very high doses, lithium is a mood stabilizer. It’s a mood stabilizing drug. But we are speaking of doses of 1,200 milligrams per day to have these mood-stabilizing psychiatric effects.

In the studies we just discussed in terms of life extension and reducing the risk of neurodegenerative diseases, we’re speaking of one milligram per day, so not 1,200 milligrams per day, but one milligram or even less, like 0.3 milligrams has been used in some clinical trials.

So lithium, is a very interesting ingredient. We also have glucosamine, glucosamine is very well known as as a substance to improve joint health. But very little people know that glucosamine has also been shown in different experiments or studies to extend lifespan in various organisms. So in the middle, you see a graph of life extension effects of glucosamine in mice. But we know that glucosamine acts on various aging pathways and aging mechanisms.

For example, glucosamine can induce mitochondrial biogenesis. So it means that glucosamine increases the amount of mitochondria in the cells, which is very interesting, because the more mitochondria you have in your cells, the better the cells can maintain themselves and so on. Glucosamine often uses autophagy and has also many other effects on specific hallmarks of aging.

Interestingly, in studies that looked in, in humans, also they have been done some big studies in Europe and US, where scientists looked at supplements and tried to see whether supplements could reduce mortality. They found, not surprisingly, that most supplements people take did not show an association with reduced mortality, but only a very few number of supplements showed an association with reduced mortality. One of these was glucosamine. People who took glucosamine, they had reduced mortality.

It’s not a cause, it’s an association, but with experiments in mice and so on, we see that is a very likely a very causal connection too. There was also a study in humans that was published in the British Medical Journal not that long ago that also saw that people who take glucosamine as a supplement, they have a reduced risk of heart disease. All in all, glucosamine is also a very interesting substance

Glycine is also an interesting  ingredient. Glycine is shown to extend lifespan in multiple different species. Glycine is a naturally occurring amino acid, so it can be found in our bodies, but unfortunately, the older we get, the more and more levels of glycine decline.

We also see that low levels of glycine have been associated with increased risk of heart disease and metabolic disorders. Glycine has also demonstrated to have effects on various biomarkers or hallmarks of aging. For example, glycine can modify the epigenome of the mitochondrial DNA, improving mitochondrial dysfunction, but glycine can also impact, for example, proteostasis, a lot of reasons why we age.

Glycine is a small molecule, and it has a chaperone function in the sense that it can stick to proteins, protect the proteins so that they get less damaged and they also accumulate less, because glycine has a chaperone function protecting proteins against damage and accumulation.

Another interesting ingredient is malate. Malate is also found in nature. For example, in apples, it gives apples their characteristic apple-like taste. Malate has shown to extend lifespan. It’s a substrate also in the Krebs cycle in the mitochondria, just like alpha-ketoglutarate as we discussed earlier.

Various health benefits have been associated with malate intake. In humans, malate has shown to improve energy and stamina and improve mental agility. We provide malate in the form of magnesium malate, because the magnesium also has various health benefits.

Magnesium is a very important mineral that’s needed by hundreds of different proteins and enzymes in our body. Magnesium also stabilizes DNA by just sticking to the DNA strand and reducing DNA damage that way, and there’s many other effects. Unfortunately a lot of people are deficient in magnesium; even if you eat quite healthy, it’s very difficult to have high-enough levels. Some studies show that up to 70% or even more people are not taking enough magnesium.

It’s a very important mineral, and ideally you take it in the form of magnesium malate because you also have the health and longevity effects of malate. Most magnesium, if you buy it in the supermarket or at the pharmacy, it’s magnesium oxide, not magnesium malate. We think malate is a much better form of magnesium to take.

Hylauronic acid is also another agreement we are very interested in, we’re fond of hylauronic acid. It’s a substance that occurs naturally in our bodies, especially in our skin. Hylauronic acid is a component of the skin that glues together our skin cells; it’s a component of the extracellular matrix of the skin. The older we get, the less hylauronic acid in our skin, and that contributes to wrinkles, among other things.

Interestingly, studies have shown if you take hylauronic acid orally, so not by just applying it on the skin, just by taking it orally, that it can reduce wrinkles and improve moisturization and so on in the skin. It can reduce aging-related osteoarthritis in various studies.

We also picked hylauronic acid for another reason because one component of hylauronic acid is acetyl-glucosamine, and acetyl-glucosamine has also shown to extend lifespan. Do not confuse acetyl glucosamine with normal glucosamine. Acetyl-glucosamine can have beneficial longevity effects different than standard because acetyl-glucosamine, for example, can induce the unfolded protein response.

The unfolded protein response is a stress response that our cells exhibit when too much protein starts to accumulate or gets damaged, and that actually activates the unfolded protein response as a way to deal with its protein accumulation, and, as you know, protein accumulation is one of the reasons why we age. One of the reasons why acetyl-glucosamine could extend lifespan is by improving protein stasis or protein homeostasis by inducing this unfolded protein response.

Then also all the interesting ingredients is rhodiola rosea. Rhodiola rosea has been used for centuries, especially in Northern Europe and Asia, as an adaptogen. It was found that it could improve stress resilience both against physiological and psychological stresses but also provides more mental and physical energy. It has been shown to extend lifespan in fruit flies, yeast, worms, all kinds of different organisms, which is interesting. It has also shown to protect the brain against damaging in rat models and other rodent models

In humans, it has shown to improve memory and learning. We also see, very interestingly, that specific components of rhodiola rosea like salidroside, for very interesting effects, including improving regeneration of neurons. There have been studies that boost in nature and so on, that the salidroside can improve the regeneration of damaged neurons. By the way, you can go to our website, Novoslabs.com, to find a lot of the scientific references. We discuss each ingredient in great detail and also provide you with some very interesting scientific references.

Of course, we also like NMN. NMN is, as you know, an NAD booster. As we get older, NAD levels decline, and it is very important in the cell. It’s responsible for a myriad of functions, including improving DNA maintenance and the maintenance or repair of the epigenome. When we get older, NAD levels decline, and that impacts DNA repair and maintenance of the epigenome.

There are various NAD boosters available, including NR, or nicotinamide riboside. We were agnostic as to whichever NAD booster we would use, NR, NMN, others, but we like NMN more than NR for various reasons. We think NR is touted a lot on the internet, because it’s also patented, the production process of NR is patented. That’s not the case for NMN. But I think that’s also one of the many reasons why NR is touted a lot as the best way to boost your NAD levels, but we don’t think so.

Also very big experts like well known longevity and NAD metabolism experts, like Professor David Sinclair do take NMN and not NR for various reasons, and on our website, we also explain the differences between NMN and NR. But anyway, NMN has shown to to mitigate all kinds of aging symptoms in all kinds of different studies. And it’s also a very interesting ingredient.

Before ending this presentation, perhaps a quick word of nutraceuticals versus pharmaceuticals. Because we believe that nutraceuticals are in fact very interesting to impact aging and that they are also very important, perhaps even better in some ways than pharmaceuticals.

The reason why I like nutraceuticals a lot is because you can use different combinations of ingredients. Compared to classical pharmaceuticals or classical drugs, it’s always, or in most cases, one drug to treat one target or to address one target, and that’s how classical pharma does it.

That’s not very interesting, because as you have seen, aging is caused by many different mechanisms, and trying to develop one drug to treat one aspect of one mechanism is not really going to make a big dent in the aging process. Ideally, use combinations of different ingredients of different substances to target multiple aging mechanisms at the same time.

You can compare it to a house that’s very worn down, if you were only going to try to repair the gutter, but you’re not going to repair the leaky basement, or you’re not going to repair the glass of the house or the walls or the attic that’s damaged or the roof that’s damaged, you’re not really going to make a big impact in preventing the house from further wearing down, and you need to fix the basement, the windows, the attic, the roof at the same time.

That’s why we believe that using combinations of different ingredients targeting multiple different mechanisms of aging is much more interesting. Big Pharma cannot really do that; they always have to pick one drug for one target.

Another reason why nutraceuticals are very interesting is time; you can go to market much faster. If you want to develop a drug, it takes 10 to 15 years, you have to wait. But with nutraceuticals, you can go to market much much faster, and that’s very interesting because there are a lot of very interesting substances already out there that have a lot of science behind them like the ingredients we just discussed, but pharma is not interested in that because they cannot be patented.

They are not interested in microdosed lithium, or alphaketogluteric acid, or fisetin because these are natural substances, they cannot be patented. We find that very unfortunate because the substances have a lot of good science behind them, and if they could be patented, they would be very big drugs, very likely, but they are just left on the sideline for that reason.

We think it’s important to give these interesting substances a chance and also to give people the opportunity to already take these substances, because otherwise, they are completely ignored by classic pharma.

They have a lot of science behind them. The science is even better, because the scientists that investigated these specific substances, they are not pharma themselves. In that sense, they are not biased, because for my industry, often they do their own experiments to test whether the drug works or not. You have a bit of an inherent bias there. Scientists that research fisetin, they don’t really have this sort of bias because fisetin, like I said, it cannot be patented.

Aging as a disease is also very interesting because nutraceuticals can really try to target aging, and pharmaceutical drugs cannot do that, because you cannot develop a drug to treat aging, because aging is not officially a disease. At the end, in Europe and in Japan, aging is not considered a disease.

So you will always, when you develop a drug, have to pick a specific disease. You cannot say, “Well, I’m developing a drug or treatment for aging,”: which is very ironic because most aging related diseases are caused by aging itself. Developing an aging drug to really go after the root cause of these diseases, you cannot really make that claim. With a nutraceutical, you can claim to try to treat aging itself.

Also, the costs are much lower in the sense of clinical trials. If you want to further corroborate your nutraceutical, you can do trials that are much cheaper than compared to classical drugs, and you can also use biomarkers that are much more interesting and more up to date.

Because often the FDA requires very outdated biomarkers to test the drug or the efficiency, like looking at cholesterol levels. We know that people get a heart attack, because of many other reasons than increased cholesterol, for example, because of inflammation, or because of senescent cells in the blood vessel walls, and stem cell depletion and epigenetic dysregulation. Also, looking at cholesterol levels as a biomarker is not that indicative. For a nutraceutical, you’re free to choose biomarkers that are much more interesting, newer, and more relevant.

In conclusion, we are at a very interesting era in the sense that we see this dawn of science-based nutraceuticals and supplements to target aging. Like I said, many decades earlier, we had to make do with anti-aging supplements that really had little or no science behind them, but that’s now changing. We see the rise of science-based nutraceutical companies to address aging. That’s great, and also for our competitors, we really applaud them because we really need more of these science-based approaches to neutraceuticals to impact the aging process.

NOVOS is not just a nutraceutical company. It’s like a longevity platform, helping people to live longer, healthier lives. As I mentioned before, we want to offer tests and management knowledge to help people to live longer. That brings us to the last part of this conclusion. We want also really to advance our understanding of the aging process by sharing knowledge on aging and how to live longer and healthier, but also by helping researchers to investigate aging and by funding aging research.

As I mentioned, parts of our profit go to fundamental aging research, because we really want to advance the field in that way. Many thanks for your attention, and if you have any questions, just shoot me an email, you can go also to our website and find a lot of relevant information and tips and insights. You can also subscribe to our newsletter, so you get regular updates and tips on how to slow down aging and live a longer, healthier life. Many thanks for your attention, and hope to see you soon on another conference and wishing you all the best. Bye.

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