Inflammation and Aging | Glycanage | Dr Gordan Lauc
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Welcome back to the Health Longevity Secrets Show with your host, Dr. Robert Lufkin. His New York Times bestselling book is titled, Lies I Taught in Medical School. See the show notes to download a free chapter. And now please enjoy this week's episode as we explore inflammation and aging with Dr. Gordon Lauk.

This week, we explore the secrets to a longer, healthier life with our special guest, Dr. Gordon Lau, a renowned professor of biochemistry and molecular biology. In today's episode, we promise to transform your understanding of aging by introducing a revolutionary approach to measuring biological age through glycosylation.

Now, unlike the familiar concept of glycation tied to sugar levels, glycosylation, on the other hand, involves complex enzymatic processes that impact our immune system and overall health. Discover how these glycan modifications can serve as a biological clock, reflecting our lifestyle changes and even reversing biological age.

Join us as we decode the relationship between age, glycans, and disease risks. Through Dr. Lauch's extensive research involving large population studies, we reveal how inflammation-driven changes in glycans can predict serious health conditions like cardiovascular disease, diabetes, and inflammatory disorders such as irritable bowel disease and even lupus.

Understand why aging is a significant confounder in health assessments and how glycan changes can provide early warnings about disease risks, giving us all actionable insights to modify our lifestyle and manage these risks effectively.

Finally, we get to explore the nuances that set glycan-based tests apart from DNA methylation clocks. Don't miss Dr. Lauk's invaluable tips on maintaining our health and reducing our biological age. Stay tuned for exclusive insights that could revolutionize your approach to aging and wellness.

This episode is sponsored by Cypox Health. One of the most common questions I get asked is which blood tests I check myself on a regular basis.

Well, I checked 17 biomarkers, but the secret is I'm able to do everything from the convenience of my home. I collect a sample with just a simple finger stick like this. You don't need to be a doctor to do it. Then I just mail it in and wait for the results. Cyfox Health makes it possible. Use the link below to get 15% off.

This episode is brought to you by El Nutra, maker of the Prolonged Fasting Mimicking Diet. If you'd like to try it, use the link in the show notes for 20% off. And now, please enjoy this week's episode. Hey, Gordon, welcome.

Thank you for inviting me. Pleasure to be here. It's so good to have you on the program, and I'm so excited today to talk about an alternative biological age measuring system based on inflammatory markers, specifically glycosylation. So

Many of our people in our audience have heard of glycation with respect to hemoglobin A1C and the damage that blood glucose can do at high levels with this glycation, age-related glycation and products. But maybe tell us what exactly is glycosylation and how is that different from glycation?

So glycosylation is something completely different from glycation. Actually, the only similarity is the name and the fact there is a glycosylate link between sugar and a protein. So glycosylation is a very sophisticated enzymatic process in which proteins are being modified with the complex oligosaccharides called glycans.

So the best analogy I usually make is that if you imagine a bird without the single feather, so just the bird without feathers, that's a polypeptide, that's a protein. And then you add feathers to the bird, which makes it completely different. It enables birds to fly. It enables birds to have different colors and so on. In proteins, this is a glycosylation.

So glycosylation is a process which practically enabled us to become multicellular. So without glycosylation, we would still be a single cell organisms. Glycosylation enabled to create the millions of different structures based on only 22,000 genes which you have. Because remember, we have only four times more genes than the E. coli.

and we are way more complicated. And one of the ways how we achieve this is that part of the protein structure are glycans, and they're not encoded in a single gene because normally there is a gene which codes for a protein, and you cannot change this protein without mutation, so it takes thousands of years to change a protein. Glycans are encoded in a network information over hundreds or even maybe thousands of genes which work together

create a glycan structure, which makes the protein different. And the key thing is, this is something you can change. You can change it your lifetime. It's changing with age. It's changing with lifestyle decisions. And the protein we focus on are immunoglobulins, in particular immunoglobulin G. So these are the antibodies. So the main weapons of our immune system, which recognize all the invaders and then takes care of them.

But antibodies, the protein part is binding to the antigen and they don't know what will antigen be. And antigen can be a virus, it can be a bacteria, or it can be a food which we eat. And the response of our immune system to the viruses, bacteria and food should be very different. And this is what glycans do.

So glycans attached immunoglobulins decide which kind of effector functions, so which kind of action will the immune system do when it binds to an antigen. So if it binds viral antigen on some kind of cell, this means cell is infected with the virus, this cell should be killed. Then the NK cells come and kill the infected cell. But if recognizes

some kind of a structure which originates from our food, and often these get incorporated in our cells, then the immune system has to learn not to kill that cell. Because if it kills that cell, then we have autoimmune disease. So you put different glycans on antibodies to tolerate the antigen. And this is very simplified, of course. It's a very complex part of the immunology. But in principle, what we know

that this is changing with age. As we are younger, actually when we are kids we are also very highly pro-inflammatory, but when in our early adulthood, so from 18-20 years on, we are really coping well with inflammation. We don't have many young healthy kids, non-obese, which are highly pro-inflammatory. As we are getting older, we have more and more problems with so-called low-grade systemic inflammation or chronic

systemic inflammation, which is underlying most of the complex diseases we have. And by large, this is regulated by glycosylation. So glycans change from structures which suppress inflammation into structures which promote inflammation. This is how we quantify this kind of aging based on inflammation. That's fascinating. It sounds like some of our other speakers have talked about...

other biological clocks that our audience may be familiar with, like DNA, epigenetic methylation clocks, which control the epigenome. And the genes don't change, of course, for the most part on the short term, but our epigenome, we can program through our lifestyle choices in our environment and our lives. And it almost sounds like

What you're describing is the proteins, which don't really change or evolve on the short time scale, but controlling the glycosylation, which is affected by our lifestyle and our choices like that, we're seeing a similar type of thing so that

in the case that you're looking at related to inflammation, we're seeing essentially a biological clock that reflects our lifestyle choices and our experiences in our life. And as we grow up and as we grow older, what you're saying is there's a consistent pattern that will determine a quote biological age that then we can use to compare with a chronological age. Did I get that right? Yeah.

that's more or less correct. Important thing here is this clock can even go in the reverse. So if, for example, if somebody who is obese loses weight, they can revert the glycan age clock. And we published a number of papers, for example, after bariatric surgery, people usually lose a lot of weight, 20, 30 kilos, and then their glycan age can go down for 20, maybe even 30 years, within a year or so.

So you can clearly see effect of improving the situation in the body, because if you lose 30 kilos of fat, you lose a lot of inflammatory processes going on there. And then you are less pro-inflammatory and we see it on a glycan clock. And some people say that glycosylation is something like epiprotomics.

meaning it's a changes on top of a protein. There is a strong interaction between epigenome and the glycum. But the thing is that glycans which we measure are encoded by the epigenome of the plasma cells which are resident in the bone marrow. You cannot read it unless you collect the bone marrow from a sample. Because epigenetic logs are very sensitive to what kind of cells are you measuring.

you'll get different things in different organs. Not for the original C4 blood block, it's multi-organ. So it's just measuring chronological age and it's extremely accurate in measuring chronological age. But chronological age, I know my chronological age. I don't need a test for my chronological age. I want to see the difference between chronological age and what is the real damage I did to myself in the last 50 something years

that I have lived on this planet. And this is what we can quantify now. We can quantify it very reliably because if you do repeated testing and you don't change anything in your lifestyle, it will change year by year. So every year you'll get one more year of a glycanogen. But if you change a lifestyle, it can improve. But the thing is, we think that we know what is healthy.

But actually, we know what is healthy for an average person, because all the research is based, you do thousands of people, you take an average and say, this is good, this is bad. And on an individual level, these things vary, especially if we talk about food and if we talk about physical activity, if we talk about sleep. For example, if I sleep less than seven hours, I don't function normally.

I have friends who sleep four to five hours a day for decades and they feel fine. Some people cannot cope with carbohydrates in the morning. Some people cannot cope with the carbohydrates in the evening. So our hormones, our microbiome, all these things make us different. And for example, my glycan is just horrible. I won't even say how bad it is. So when I learned that, my first response was, okay, let's wait it out.

So I was hiking four or five hours a day in the mountains. I lost something like 10, 12 kilos. I was fit, but you know, my feet were hurting all the time. My muscles were cramping because I was over exercising and my glycan did not improve much. It improved a little bit, just maybe one year for all that effort.

And this was long time ago. This was nearly 10 years ago when I started doing that. And in the meantime, we did a lot of studies. We have thousands of people exercising. And we learned that majority of the middle-aged people, when they start to exercise, they overdo it. They exercise too much. And actually, they make themselves even more pro-inflammatory. And there are only some trainers which can really optimize well physical activity and relaxation.

which you need. You need relaxation between physical activities to have positive impact. Also for the food, we have a very interesting study. We had a thousand people on a low-calorie diet for two months, 800 calories, two months. So most of them lost over 10% of their body mass. And then they were transferred to one of the five maintenance diets, five different combinations of macronutrients, high glucose, low glucose, high protein, and so on.

And on each of the five diets, some people get better, some people get worse. So there is no magic diet which works for everybody. And if you read books, if you look at the Internet, some people will claim keto diet is a solution for everything. You go to carnivore, you'll heal all diseases. And this is probably true for 20 or 30% of people. Some people will have kidney damage from too much keto.

So we are all different. We have to learn what is good for us. And one thing which a glycan age can do, it can show you in a few months whether what you are doing is good or not. And since glycan age is available in over a thousand clinics globally already, we have learned, for example, that often people overdo it.

you eat keto, you take supplements, you go for ozone therapy and some kind of intermittent fasting, and some metabolisms cannot cope with that. And you solve the problem just by taking something out. Don't try that hard. Maybe you should sleep an hour longer a few days a week instead of going to the gym. So it really gives a physician a tool to personalize intervention.

Because as a physician, when you have a patient, you can just give them some kind of standard advice at the moment. Because you don't know the metabolism of the guy, you know, the genome of that person. But in a few months, you say, okay, this does not work. Let's try something else. And classical medicine,

has this as a kind of a routine approach. You are just, you're giving a drug. If drug doesn't work, you give another drug. If it doesn't work, you give a third drug and so on. In a preventive healthcare, people don't do that. So if you send your patient in the gym and he doesn't get better, you will only tell him, go more in the gym. You will not tell him, try something else. So I think this is where this whole set of new biological tests

biological age test would help is to personalize every intervention. Yeah, that is so important, that aspect of personalization. That's really the key to all these lifestyle innovations, just as you say that what works for one person may not work for the other. So we all have to filter the advice through our own needs. And I want to come back to that. But

Before we do, let me go back. And you've chosen inflammatory markers for the glycan age analysis. And I can think of a lot of reasons why you did that. Why did you choose inflammatory markers versus other types of markers? What was your thinking there? So I'm a glycoscientist.

I analyze protein glycosylation and we do it in a large cohort. We analyze over 200,000 people. And our intention was not to develop the biological age block. Our intention was to develop biomarkers for different diseases. But what we learned when we started doing that is that age is such a strong confounder that the older healthy person will be similar to much younger person with the disease.

So we didn't plan to develop this type of test. We just stumbled onto it by looking at the large cohorts, population cohorts, people aging, people with the disease. And then we realized that actually, incidentally, you know, the original Steve Horvath epigenetic block and the glycan block were published in the very same day. It was December 10th, 2013.

And at that time, we were not aware of the Steve Horvath clock yet. And then we even suggested that the glycans can be used in forensics to identify the age of a blood sample found on a crime scene, because my lab also has a forensic lab.

But then, of course, epigenetic clock is way more accurate in predicting the chronological age. But then we learned that the glycan age clock is much better in predicting effects of lifestyle on biological age. So this is how we came to that. And then only later we realized that this is

underlying inflammation, which is driving the change in glycans. So we did not look into inflammatory markers. We did not look into aging. We were looking at glycans and trying to understand what happens with glycans in a disease. And then we learned this effect of aging, this effect of inflammation, this is disease. And for example, many inflammatory diseases like a

IBD, arthritis, lupus, they have very similar changes in vitals, which are showing this general path of chronic inflammation, which is then manifested as a specific disease. And, you know, as you know, as a physician, disease names are based on symptoms and the location, and they were determined 50, 100 years ago.

So they don't include pathophysiological mechanisms. So the same disease name can be a consequence of five different pathophysiological mechanisms. And when you give drugs, drugs do not act on a disease name. They act on a pathophysiological mechanism. That's why you have to find which drug helps. And this has to do with lichens. We try to stratify people and find who will respond to a specific drug, who will have a worse and better response.

disease prognosis and good thing with glycans is as they're affected by genes, environment, lifestyle, they change up to 10 years before you actually get diagnosed with the disease. For example, for cardiovascular events, heart attack, stroke, for diabetes, we can see changes in glycans up to 10 years

before you actually end up with the disease. So you have 10 years to change your lifestyle and you can use glycans to monitor this change. And we have shown, for example, if you are going toward the abetis, some specific glycans will gradually change. And then if you start losing weight, which we know it will reduce your chances of the abetis, also your glycans go backwards. So it's a kind of a real-time monitoring of disease risk.

compared to genetic disease risk, which you cannot change. So if your genetic risk is two times higher, it's two times higher. Glycan risk is something you can modify. And then you can track yourself and see, okay, I did good or I'm not doing it. Yeah, that's such an important point, being able to modify the risk and take action with our lifestyle. We can't emphasize that enough. And also the point about inflammation being at the root of many diseases. I mean, I used to think of

if you look at the main diseases that determine our longevity, you know, it's a short list. Most of us will die of cardiovascular disease, cancer, Alzheimer's disease, and, you know, one or two others. But I used to think of those as very separate diseases and including diabetes and other things. And now, of course, we understand that they all have an underlying metabolic inflammatory component, which is very, very strong. And as you say, you know,

Well, Alzheimer's is like type 3 diabetes in some patients. So there's a strong glucose metabolism association. And as you say, the important point is with tests like glycan age and other ways we can look at that, that these diseases don't suddenly just start the moment the doctor diagnoses them. But diabetes...

The road to diabetes occurs years to decades beforehand. Same thing with Alzheimer's disease, cardiovascular disease, all of them. So having tests like GlycanAge where we can get an early warning is so valuable. We have to be careful here. GlycanAge is registered as a test for biological age. It doesn't come with any kind of medical claims.

we can only say, you know, these structures which are driving your glycan age have been associated with these specific diseases in research studies. This is what glycan age can say. You as a physician to your patient can make a more exact recommendation and say, okay, this is indicative of this. But that's your...

you as a physician, you can do it. GlycanAge as a company can only tell you something about your biological age and maybe warn you about some papers which have been published because to be able to predict diseases, and in particular in Europe, which has this new IVDR directive, you have to go through the process of validation, which will then confirm that what you are saying is really true because we don't want to scare people into things

which are not medically justified at the very moment, meaning there is no diagnostic claim.

Yeah, that's a very good point. Language is important and we need to be very clear on our claims and what we're saying. And we're not saying that glycan age or these other tests will necessarily predict Alzheimer's disease or these other things, but it may show a risk for it or a tendency that we can... I think the largest value in testing glycans and glycan ages

that you can monitor changes and see whether your risk is increasing or decreasing and the things which you do, whether they have positive or negative impact on you. Because in the entire longevity field, one of the key problems is, you know, everything is based on advertising because none of us can actually know the effect

until we die, you know, until 20, 30 years later. So unfortunately, there are different products which come to the market, they are heavily advertised, people take it without any evidence that it actually works. And this type of a test can show whether it works or not, at least in one component, and this is regulation of systemic chronic inflammation.

So, and we did a number of different supplements, which we never published because the producers of these supplements were not happy with the results. So they didn't want to show the result. So I think glycanogen as a test from one aspect, it's fantastic because it can show you whether you are working, whether what you are recommending or doing is good.

but also it makes some people unhappy because some people are happy selling things which do not work to their patients. And then you do the test and if it doesn't work in one person, doesn't work in another person, then maybe what you are selling is actually not working. And in this way, glycogen is making enemies in the field also because when you show that some things do not work, it makes some people not happy. Yeah, the...

That's a really good question. As a consumer or user, we're all consumers of longevity products to the extent that we're all concerned about our longevity and we pay attention to our health. So as someone interested in longevity products,

And there's so many biological clocks out there. We mentioned DNA methylation clocks, you know, their brain age clocks with MRIs there, you know, you can do a clock on practically any marker that consistently changes over time in a reliable fashion with aging. So maybe you could speak about...

the value of glycogen age compared to these other clocks? In other words, when should I use glycogen age to look at glycosylation for a biological age versus DNA epigenetic methylation or some other clock? So when do I do which one? So for the end consumer,

it's very hard to decide because they don't understand science, they don't know how to evaluate different clocks, so it comes down to marketing. This is why GlycanAge is trying really hard to work with serious anti-aging clinics or longevity clinics where there are specialists who know how to read research literature. And the only thing I tell to them, look at the research papers.

Because we have over 100 papers showing that this Glycan-H test and the glycans on IgG are highly relevant for diseases, that they change with the lifestyle interventions, that this was done on over 200,000 people so far. For all other tests, besides the original Steve Horvath epigenetic test, there may be one, two, three papers.

I love epigenetics, I even teach part of epigenetics. But every year there are three or four new epigenetic tests on the market. So if there are so many new epigenetic tests, which one is really good? And then you can use an approach which Andrea Meyer is doing in Singapore. She's buying three tests and looking for the median. Why these three? Why not the other three? Why the median? So epigenetics still needs a lot of research.

before we could be able to interpret all these new tests. Some of them are maybe fantastic, but this still has to be shown. For most other tests, it would be one or two papers.

research papers, large studies which can show something. And if you look in a self-perspective paper which was published by the Consortium for Biomarkers of Aging, it very clearly identified that the Glycan-Age is the only commercially available test which is linked to a number of different diseases. So I think if you want to stick to science, if you want to really do what has a scientific backing, it's the Glycan test.

Okay, so let me see if I understand that correctly. So basically what you're saying, it's not like there are certain indications where glycogen H will be valuable. There are other indications where DNA methylation epigenetic clock will be valuable.

What you're saying is that glycogen age is, is the most reliable test and it's, it's really a replacement for DNA methylation clocks, right? So there, it's not like one has a value in one situation. Another has value in other situations that glycogen age has been, if I understand you correctly in your, it has shown its effectiveness and these other clocks have not. So it's,

We shouldn't depend on them at this point until more evidence comes in. So for epigenetic blocks, there is not a single epigenetic block. So you cannot make it generalized. So we did a couple of papers where there was very little correlation and acceleration between the epigenetic and the glycan agent.

We did recently published a paper when there was this rejuvenation of rats with a fraction of pig plasma and we did it together with Steve Horvath and then in this situation both epigenetic, the Steve Horvath epigenetic test and the GlycanAge test rapidly went down. So there are some examples where both tests will change. So for GlycanAge

The key difference between the glycan age and epigenetic test is epigenetic test is still just an information. You are reading some CPG sites on DNA. You don't know the function of these sites. And then you make interpretation based on the correlations in a large size. This is one disadvantage of the glycan or of the epigenetic test. The other disadvantage of epigenetic test is that most commercial tests

are using a relatively cheap technology to analyze DNA methylation. And if you take even the same sample, send it twice for the analysis, you will get a different number. So they have a measurement error which is relatively large, and they're good for research studies when you have thousands of people and the measurement error will kind of level out. But if you test yourself epigenetics repeatedly, you get different numbers.

which are randomly going up and down. So for glycans, we know what these structures do. So there are molecules which regulate interaction between globulins and they are activating pathways. And we know that if one structure goes up, this is pro-inflammatory. If other structures go up, it could be suppressing the inflammation.

So you know that these are the molecules which actively act on inflammation. So if glycogen goes down, your inflammation is going down. There is very solid science and it's not science only coming from our lab. There are dozens of labs in the world which do the same thing. This is not something which can be debated. And the other thing which we know is that if you do an intervention which is known to be healthy, like

regular moderate physical activity, not too much stress, healthy diet, your glycans are showing they're going down, they're becoming less pro-inflammatory. So a lot of science, mechanistic aspects, a lot of reliable data showing the interpretation of the glycan changes. This is why it is the best test. The only problem that this test has is that there is currently one lab in the world which is doing it. This is my lab.

So we do 50,000 to 60,000 samples a year. So it's not a small number, but it's still limited in my lab, which is located in Zagreb, Croatia. So if you look from the US, this is some kind of a strange lab in a strange place of world called Europe doing something. Why should I send something to Europe?

So we'll be opening the US lab very soon. We're opening the Abu Dhabi labs, probably even Singapore soon. So it will be more labs. This will become more widely available. So I think in a few years, you won't be asking me this question anymore.

I like that. Yeah. And talking about the future, I mean, one, as a user of these tests myself, one negative effect, I think that, you know, or one factor to consider is certainly with

with glycogen and these other biological clocks right now that impacts how we use them is their cost. Uh, that, you know, a few hundred dollars is, it's not something that we can, you know, that many people can afford to do more than, you know, relatively infrequently as you do looking in your crystal ball in the future. Do you see anything coming down the pipeline? You're obviously scaling, um,

Will we expect to see the cost of this coming down or are there any alternatives that we could use as maybe a subset of glycan age on a more frequent basis and then do the full clock once a year or twice a year or something like that? We are really trying hard to deliver the high quality data. And for example, what we are doing, we are measuring each sample three times from the blood stain to the number.

So immediately the price could go by a factor of three if we don't do it in a triplicate. But then the measurement error will be a little bit larger. So something what could be potential kind of information product, you want to have a light glycan age, which could be five years up and down, you do it for maybe one third of a price.

Or, you know, a couple hundred euros or dollars, that's actually not a very expensive diagnostic test, at least for a US. So if it comes under the reimbursement model, so it becomes a regular diagnostics for measuring low-grade chronic inflammation, you don't call it a glycan age, you call it the IgG glycone composition, then this is not that expensive. And of course, with the volume, prices will go up.

So the problem with the glycan analysis is that my lab is currently doing approximately 80% of the global output of high-tropical glyconics. So all the consumers, everything that we are buying is being made in a small series. So if this goes into the millions, that all the consumables will become cheaper, everything can be scaled up, prices can go down. But this requires scaling.

So with scaling, the prices will go down and then the labs could do it as any kind of routine testing. So in theory, this is not much more expensive than any kind of immunostatic chemical test or other tests which are being done routinely in labs. Just this is still not diagnostic because the machines are not diagnostic, the reagents are not diagnostic. It takes time to move it to that direction.

And just to be clear, I think in the United States, this is glycan age type clocks or other biological clocks. To my knowledge, the DNA epigenetic clocks are not reimbursed typically by insurance. Is that correct? This is not reimbursed because insurance is reimbursing the disease diagnosis and disease management. Age is not a disease.

So if age becomes classified as a disease, then it could be in this way. But the same type of test, IgG glycol composition, which is used to calculate the glycan age, can become a diagnostic test. And we are actually launching a similar test in Europe

probably by middle of this year, which would be a diagnostic test for IgG glycol composition, but still to become reimbursed by any kind of a national or private insurance company, it requires very complicated decisions.

Yeah, it's definitely an involved process. Well, I want to be respectful of your time, Gordon. Maybe you mentioned that with all your experience and looking at these lifestyle things and this amazing clock that you have, would you share maybe one to four quick tips with our audience before you leave? I can share general tips, meaning...

Regular moderate physical activity, healthy diet, not too many carbohydrates, good sleep, not too much stress. But, you know, we can't afford all of that in most of our lives. So what glycan age can help is pinpoint the thing which is the most important for you. And then maybe if you sleep an hour longer, maybe you can go to gym once a week and not three times a week.

Or somebody else maybe can sleep a little bit shorter and go to gym three times a week, but avoid fruits or something like that. For example, what I learned that I thought the fruits are healthy. Fruits are poison. You know, so much sugar. Okay, depends on the quantity. People need to eat fruit, but I used to enjoy too much fruit.

And then when I saw what fruit is doing to me, now I'm actually cutting down fruit. Because, you know, my mom taught me, you know, fruit is good. You should eat fruit. Maybe some berries, blueberries are fine. But, you know, oranges and such things, it's a sugar bomb.

Yeah, yeah, I said, I have a certain awakening for me to that certain fruits have tremendous amount of sugar and some of the fruits are relatively low sugar and can be good but yeah that's a great point. Well, I want to, I want to respect your time here Gordon thanks so thanks so much for taking, taking time with us today. Maybe you could share how people can get in touch with you your website at

and social media contacts, if you don't mind. We'll put it in the show notes as well, but if you could just tell people who are listening only, they could hear that. It's glycanage.com and also all other platforms like Instagram or LinkedIn, Twitter. It's glycanage. Very glycanage, one word.

That's easy. I like it. Well, thank you again, Gordon, for spending time with us and telling us about the fascinating work you're doing. Thank you for the invitation. It was a pleasure to chat.

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