Glycans- The Next Biological Longevity Clock?

DNA methylation clocks are all over the news for comparing biological age with chronological age in longevity assessment. The next great biological longevity clock may be based on something called glycans. Today we speak with the leading expert on the subject. 
Gordan Lauc PhD, is Professor of Biochemistry and Molecular biology at the University of Zagreb and Co-Founder and Chief Scientific Officer at GlycanAge. He graduated from the University of Zagreb Faculty of Science, and obtained his PhD in Biochemistry from the University of Zagreb.

Take home points:

Glycans have been called the third revolution in evolution. All our basic DNA information is encoded by 4 nucleic acid building blocks in a linear fashion. There are even more possible combinations in the way that our proteins are encoded by 20 amino acids [also in a linear fashion]. Glycoproteins allow orders of magnitude more possibilities of information storage complexity with over 2000 forms which can be combined in a branching, nonlinear fashion. 

Glycans are sugar molecules that surround and modify proteins in your body. They respond to your lifestyle choices and indicate the inflammatory state of your immune system, which in turn determines to your biological age. Glycans have a large influence on your unique biology and are regulated almost equally by our genes on one side and environment and lifestyle choices on the other.

So life on this planet, began as RNA world. So ribonucleic acids were the first molecules which were containing information and replicating this information. And then, as evolution was happening, ribonucleic acids recruited m&s, it’s to make proteins. Because for nucleic acids, there are only four building blocks, they’re relatively similar, very hard to many different to make many different structures. For proteins, we have 20 amino acids. So there’s a lot more information which can be stored there. And the number of structures which can be made, is very different. But then, when the life became multicellular, we became more and more complex. And when we look only in genes, and every protein is encoded by a gene, so for every protein, we have a gene which we inherit from our parents, bacteria, which is the simplest organism would have around 5000 genes. And even when I was studying, we were taught that humans have at least 100,000 genes, because we are so much more complicated than bacteria. And but when we sequence our genome, we learned that we have approximately 20,000 genes. So humans are only four times more complicated than bacteria. And we have trillions of cells, these cells have to differentiate they have to talk together. And actually what enabled creation of multicellular life was invention of protein glycosylation. So glycans are made in a process called glycosylation. They are not based on a genetic template, so you don’t make a glycan based on a template in your genes. But it’s in a complex network interaction of hundreds of genes and this structure Make our total set of different molecules, several orders of magnitude larger. So we have approximately 20,000 genes, maybe around 100,000 proteins, but we have 10s, or hundreds of millions of different glycoproteins. So this is why we call it the third revolution in evolution. The first was RNA, the second were proteins. And the third are the glycans.’

‘So both epigenetics and like correlation glycosylation is inflammation. So it’s not only the amount, it’s the the arrangement, it’s a specific site, which either methylated or not, and the same is for glycosylation. So glycosylation is a creation of specific structures, or each of these structures contain information and perform function. Something what people often confuse, is glycation. And glycosylation. So glycation, like HB a one C, or somewhere they call it only eight. I think once the or whatever. Usually Americans have short names. So HB one C is a glycated hemoglobin. Hemoglobin, which reacts with a too much glucose in your blood creates this HB one C. And this is the process which is chemical which has nothing to do with information, it’s just a biomarker of too much glucose in our blood. glycosylation has nothing to do with that. Besides being chemically related. glycosylation is a process, which is regulated on multiple levels. For example, for immunoglobulin G, which we study a lot, these are the key antibodies we have in our body, we know that it’s over 40 different genes, which work together to make a decision about it glycosylation. And these genes are very important for different diseases, and people who have kind of glycosylation changed in a way to be more pro inflammatory. They will develop these diseases easier. Then people who have glycans which are more suppressing inflammation. So these are functional parts of a protein, which do a specific work.’

Examples -Blood groups ABO are glycans

Post translational-make protein 

Glycans modifications of proteins lipids and even DNA by sugar

Nonlinear branching oligosaccharide 

    Glucose-monosaccharide-

Post translational modifications-

     Phosphorylation

     Glycosylation

AGE- advanced glycation end products——reaction glucose and proteins- not the same as glycosylation.

Immunoglobulins- older get more pro inflammatory glycans-

Igg glycosylation suppress inflammation

Human glycan project

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Robert Lufkin MD 0:01
Welcome back to the health longevity secrets show with Dr. Robert Lufkin gli cans are being hailed as possibly the next great biological longevity clock. Today we speak with the leading expert on the subject. Dr. Gordon allowes is a professor of biochemistry and molecular biology at the University of Zagreb and co founder and chief Scientific Officer at glycan age. He graduated from the University of Zagreb Faculty of Science in 1992, and obtained a PhD in biochemistry at the University of Zagreb. In 1995. Health longevity secret show listeners who wish to try the glycan age longevity clock on themselves can receive a 20% discount by entering the code. RobertLufkin no space in the middle at the glycan age website, and we’ll have a link in the show notes as well. Now please enjoy this interview with Dr. Gordon, louts. Hey, Gordon, welcome to the show.

Gordan Lauc PhD 1:09
How are you thank you for the invitation.

Robert Lufkin MD 1:11
I’m so excited to learn with our audience today all about glide cams from really the world expert on this subject. But before we dive into that, maybe we could just take a moment and tell us a little bit about how you came to be so interested in this fascinating area.

Gordan Lauc PhD 1:32
Well, it was actually more an accident, which happened 29 years ago, I was doing my PhD. And at that time, my topic was physical biochemistry of an enzyme and I was purifying a protein. And experiment failed on Friday afternoon. And at that point, I asked my boss, okay, I have nothing to do over the weekend, give me something to do. And he came with a brand new set to analyze glycans, which was never done before. And I did it first time, nearly 30 years ago, and I keep doing it for the last 30 years. It’s a lot of fun.

Robert Lufkin MD 2:17
Oh, that Oh, that’s great. I, I I’ve heard so many interesting things about the subject. I’m really looking forward to this deep dive of her glycans, as described as maybe a good kind of sugar in an era of low carbs. I’ve also heard your your great paper in frontiers in genetics, that you wrote a few years back on glide, Cannes, the third revolution in evolution. So perhaps, we could start off by just telling our listeners about what the first two revolutions were and then how glycans are the third revolution.

Gordan Lauc PhD 3:00
So life on this planet, began as RNA world. So ribonucleic acids were the first molecules which were containing information and replicating this information. And then, as evolution was happening, ribonucleic acids recruited m&s, it’s to make proteins. Because for nucleic acids, there are only four building blocks, they’re relatively similar, very hard to many different to make many different structures. For proteins, we have 20 amino acids. So there’s a lot more information which can be stored there. And the number of structures which can be made, is very different. But then, when the life became multicellular, we became more and more complex. And when we look only in genes, and every protein is encoded by a gene, so for every protein, we have a gene which we inherit from our parents, bacteria, which is the simplest organism would have around 5000 genes. And even when I was studying, we were taught that humans have at least 100,000 genes, because we are so much more complicated than bacteria. And but when we sequence our genome, we learned that we have approximately 20,000 genes. So humans are only four times more complicated than bacteria. And we have trillions of cells, these cells have to differentiate they have to talk together. And actually what enabled creation of multicellular life was invention of protein glycosylation. So glycans are made in a process called glycosylation. They are not based on a genetic template, so you don’t make a glycan based on a template in your genes. But it’s in a complex network interaction of hundreds of genes and this structure Make our total set of different molecules, several orders of magnitude larger. So we have approximately 20,000 genes, maybe around 100,000 proteins, but we have 10s, or hundreds of millions of different glycoproteins. So this is why we call it the third revolution in evolution. The first was RNA, the second were proteins. And the third are the glycans.

Robert Lufkin MD 5:29
Wow, that so let’s see if I can summarize that. So the DNA, as we learned about has four base pairs, and it’s a linear arrangement of information. The each each DNA, each gene sequence, specifies one protein in some cases, not all, more or less. And the proteins are encoded by 20 different amino acids, also in a linear fashion. And now, the next revolution is a layer of information on top of the proteins that is the glycosylation. And I understand what you’re saying that that is not linear, that in other words, it it’s exponentially more complex. And that’s that is the the beauty and the power of glycosylation as it is containing information.

Gordan Lauc PhD 6:26
So we estimate that there are approximately 2000 different glycan blocks, which can be added to proteins. So you can have one protein and then attach 10s hundreds of different glycans. And there can be multiple vehicles. So even for simple glycoproteins, a single polypeptide sequence This is a protein part can be converted into hundreds of different glycoproteins by adding different glycans. So there’s a huge layer of information, which we are all using in different ways. We use it for our immune system, we use it for development, we use it in our brain function, and so on.

Robert Lufkin MD 7:10
So is it is it fair to say that on the show, we’ve we’ve had several speakers talk about epigenetics, and we’ve learned about, you know, DNA methylation and histones and RNA as ways of modifying epigenetic modification of DNA. What you’re saying is, this is almost a sort of epi proteomics, if you will, it’s a glycosylation of the proteins in a much more complex fashion potentially, then then the epigenetics, but is it fair to say that, this this epi proteomics is also influenced by our environment in a similar way that, that the epigenetics is, so it’s a reflection of our lifestyle and, and what happens to us in our lives?

Gordan Lauc PhD 7:58
Yes, but actually even more so. Because, for glycans, there are three key components which decide about their structures. One is genetics. And most of our glycan composition is between 30 and 50%, genetically encoded. So people are different than their glycans are slightly different, then there is a strong epigenetic component. So epigenetics is kind of memory of past events. What’s happened before in your life gets encoded in this epigenetic modifications to each make your genes more or less active. And then there is a third component and this is direct environment. epigenetics is also a bit affected by direct environment. If you eat special food, you get more or less methylation and so on. But for glycans, it’s even more emphasized, because glycans are chemical related to glide with sugars, which we eat. And this energy metabolism is directly talking to the glycosylation. So people who eat more carbohydrates will have a little bit different glycans than people who don’t eat carbohydrates. So also the current environment, the food actually when the thinking we do is affecting like regulation, so three components, genes, this is our memory from millions of years, epigenetics, this is our lifetime memory and direct environment affect the glycosylation and decide about the individual biases.

Robert Lufkin MD 9:40
And back to the comparison with epigenetics again, one of the for many people non intuitive aspects of DNA methylation as a as a mechanism for for epigenetic modification is that with time over with aging, it’s not merely the increasing accumulation of methyl groups to to modify the DNA, but it’s rather a rearrangement of the methylation groups, and there’s no net methylation differences in many cases, but it’s specifically the way they’re organized. Is that true with glycosylation? with aging? In other words, is it it’s more a rearrangement? Or is it just as you get older an order you get more and more like oscillation like rust on a, you know, on a bridge or something.

Gordan Lauc PhD 10:34
So both epigenetics and like correlation glycosylation is inflammation. So it’s not only the amount, it’s the the arrangement, it’s a specific site, which either methylated or not, and the same is for glycosylation. So glycosylation is a creation of specific structures, or each of these structures contain information and perform function. Something what people often confuse, is glycation. And glycosylation. So glycation, like HB a one C, or somewhere they call it only eight. I think once the or whatever. Usually Americans have short names. So HB one C is a glycated hemoglobin. Hemoglobin, which reacts with a too much glucose in your blood creates this HB one C. And this is the process which is chemical which has nothing to do with information, it’s just a biomarker of too much glucose in our blood. glycosylation has nothing to do with that. Besides being chemically related. glycosylation is a process, which is regulated on multiple levels. For example, for immunoglobulin G, which we study a lot, these are the key antibodies we have in our body, we know that it’s over 40 different genes, which work together to make a decision about it glycosylation. And these genes are very important for different diseases, and people who have kind of glycosylation changed in a way to be more pro inflammatory. They will develop these diseases easier. Then people who have glycans which are more suppressing inflammation. So these are functional parts of a protein, which do a specific work.

Robert Lufkin MD 12:30
Before we get into the inflammation, let me underscore the point you just made that when we’re talking about Bly cans, and this sort of epi proteomics, if you will, that’s glycosylation. And that is that is different from glycation, or the ag e that our audience has heard about for advanced glycation end products. That’s, that’s different than what we’re talking about here. Correct. That’s glycation versus glycosylation.

Gordan Lauc PhD 13:06
These are two completely different things to glycosylation in the regulated enzymatic process. glycation is a chemical reaction, which tells you that there is too much glucose in your body, and that somebody is on a path to their betas

Robert Lufkin MD 13:20
in glycation is almost like rust on the it’s exactly. Like constellation, on the other hand, is information storage, and it’s directed sort of it’s directed information. Now on to inflammation. Is that the primary longevity risk factor that glide can’t encode, are they are they associated with other types of aging phenomena or chronic disease phenomenon? Or is it all manifested through primarily inflammation markers.

Gordan Lauc PhD 14:00
So if we talk about glycans, in general, there are so many different glycans and so many different proteins that this is not possible to generalize. But what we do a lot of research on is glycans on immunoglobulin G, and when on globulin g is the main class of antibodies, and we know that its activity is regulated by glycosylation. So, there are specific forms of glycans which can be added to idg, which then directed to one type of receptors or different likens directly to other type of receptors. So, this single molecule can be either pro inflammatory, or anti inflammatory, depending on which glycans it has. So, immunoglobulin glycans are one of the key regulators of inflammation. And we know for a long time for example, if you take immunoglobulins from a young and healthy person It can be used as a drug to suppress inflammation in some inflammatory diseases. Or even long time ago in former Yugoslavia, communist politicians were using it just to extend their lifespan, they were giving young immunoglobulins to make them feel better, because they’re suppressing inflammation. And by suppressing inflammation, they save so much energy, which we normally spent for low grade chronic inflammation. Because if we go step back, what is inflammation? So inflammation is a process of rebuilding something, which is wrong. Normally, we activate inflammation if there’s some kind of infection. So there are bacteria growing in part of our body, our neutrophils come in, they kill everybody, everything, they just shoot poison on that area, kill the invaders, and then you rebuild this part of your tissue. So we all know, you know, when we get a small cut or some kind of infection, then we have a red swelling. This is blood coming in killing everybody. And then this disappears in a few days. So inflammation is good, if it is acute. But what happens with aging is that there’s so many small, inflammatory processes everywhere in our body, that it is first consuming huge amount of energy. And second, it’s making many small scars. So each inflammatory process, there is rebuilding, and not everything is being done perfectly. And too much inflammation generally leads to different types of damages. And it is now generally believed that inflammation is underlying most chronic diseases, which are the main burden today, cardiovascular, cardio metabolic inflammatory diseases, even people think that Alzheimer’s is inflammation of brain. So definitely, since we are living for as long as we live now. And again, we have to remember that biologically, there is no selective pressure to keep us alive after the reproductive age. So all the biological mechanisms were optimized to keep us alive. While we are producing children. When we stopped producing children, we were just living kind of a bonus time, which we got by healthy living, sanitation, medication, and so on. So there is no evolutionary pressure to keep neither of us alive at the moment, because we’ve done our job in making babies. And then evolution, or not evolution, inflammation kind of gets loose, too much inflammation. And this is also a result of too much food, we mostly eat too much way too much, we could survive with much less food. And also the the sedentary lifestyle. This old promotes inflammation. And this too much inflammation is believed to be one of the major drivers of aging, there is a process called inflamm aging, which is kind of a vicious circle of inflammation, more damage, more inflammation, which then ends up in a disease. And glycans are very important there. So if we have immunoglobulin glycans, which are suppressing this inflammation, then we slow down aging, we have less risk to develop different chronic diseases. Generally, we feel better and we are younger.

Robert Lufkin MD 18:50
There is certainly an epiphany for me, learning how inflammation is like, as you say, is underlying essentially every major chronic disease we face and that things like brushing our teeth to decrease dental inflammation can actually lower our risk of Alzheimer’s disease and dementia and heart attacks and other things. The other fascinating thing, which you mentioned about inflammation was that it’s all not good or bad. In other words, that acute inflammation is is good and necessary for handling certain types of attacks on the body. But chronic inflammation is is bad in that that seems to mirror what we’re learning about stress also as a longevity risk factor. In other words, acute stress for me says, you know, saunas, ice baths, exercise, those acute stresses are actually beneficial and healthy, but chronic low grade stress with glucocorticoid elevations, that is the dangerous, damaging part. So it’s It seems to be stress and inflammation have that that same feature that the acute acute is good and maybe even necessary for survival. But the chronic, indolent low grade, stress or inflammation can be can be very damaging and, and the large part of the inflammation you say is mediated through the glycosylation of the idg that you’re seeing on that?

Gordan Lauc PhD 20:29
Yes, we definitely see, for example, if people have an inflammatory disease, they will have more of these inflammatory life. And in most of the diseases, we see changes in glycans, five to 10 years before the disease develops, because, you know, disease is the kind of endpoint. So something is so badly damaged, that we feel pain, that something is not working. And then we ask for help. We go to physician and then we get some kind of diagnosis, meaning a name for our disease, diabetes, research of colitis, arthritis, whatever. But, you know, this not just didn’t, this did not happen in a minute, that did not happen in a day This was developing for decades. And our body is made to compensate for all the problems. And for a long time, it was compensating, compensating, compensating. And then at one point, it couldn’t anymore. And usually, this is the point of no return. So once you have a fully blown Crohn’s disease, there is no cure, you can just alleviate the symptoms, you can make people feel better, but they will be sick for the rest of their life. But this is why we call it a chronic disease. And the idea with DRI and many other people have is, let’s try to find this processes early. let’s identify it at the level of only a subtle molecular change, some molecules are not functioning properly, because then we still have plenty of time, maybe five to 10 years to modify lifestyle, take some kind of preventive therapy and avoid disease do not allow it to fully develop into disease. And this is where we think glycans can help a lot. And because, for example, if we take the the main killer today, these are cardiovascular diseases, we can see glycans changing five to 10 years before people develop hypertension. Because before people get heart attack, before they get stroke, we see glycans already changing. And we also see the same thing for diabetes, but different glycans, not the same glycans as for cardiovascular diseases, and we can use it as kind of a motivator to help people change the lifestyle, because we all know, what are the healthy lifestyle habits. Now, if you don’t eat too much, this is healthy. If you eat too much, this is not healthy. If you exercise moderately, this is healthy. If you exercise too little or too much, this is not healthy. If you sleep enough, if you’re not under stress, these are all healthy things. But it’s so hard. You know, it is so hard not to be under stress not to eat to regularly exercise, and people generally don’t do it. And they don’t do it because the bill is coming so late. Now, I will pay for my mistakes in 20 or 30 years, I’m not going to skip that cake, because of something what will happen in 20 or 30 years. But today with all these smart things which are tracking us or with the molecules which we can measure, you can get much feedback much sooner. For example, we have this glycan age test of biological age, which was developed in my lab. And of course, I do have some commercial interest in that. So you have to judge what I’m saying I am definitely impartial here. I’m not impartial here. We know that if you live a healthy lifestyle, these glycans will improve. And when I see for myself, that when I lose weight, my glycan is going down. This helping me to motivate myself to control what I’m eating in the next few months. So it’s, I think it’s definitely one good way of measuring what is happening and how what I’m what I’m doing at the moment. is affecting me at the molecular level. Because this is something I cannot see in the mirror.

Robert Lufkin MD 25:06
Yeah, that’s such an important concept, the idea of biomarkers or tests being motivational factors for helping us stay on the right path in our lifestyle. And the other point you made is is game changing in medicine that we’re seeing that diseases that we used to wait until they like dementia, you wait until people have cognitive impairment, but we now know that there are changes in parts of the brain like the hippocampus, that can be measured with an MRI scan, and you can see hippocampal atrophy or loss of volume in that 10 years before the Alzheimer’s disease prevents presents. And so people can be motivated to change that. And like you say, with diabetes, if you wait till the the glucose rises, which is the diagnostic criteria for diabetes, we know that 10 years before the glucose rises, the insulin has already become abnormal, but most people don’t check fasting insulin. But with a test like that, or with glycan age, we could provide that information to people and really motivate them. So let’s let’s let’s talk about clocks and biological clocks. And how, how is we’ve talked in other presentations about the value of longevity clocks for motivating people for longevity programs. How does how does a glide glycosylation clock differ from DNA methylation clock?

Gordan Lauc PhD 26:36
So we came to that point from completely opposite direction. So we were in my lab and I have a large lab with over 50 people working in it. We were interested in what happens with glycans in people who have a disease. And we already analyzed over 150,000 different people from different cohorts, people were studying different diseases, I just emailed them, they send their sample, we analyzed the glycans. And then first thing we learned, glycans change a lot with age. Because we just realized we cannot take no Healthy People which have average age of 40, with a sick people of average age of 60. And compare them because they will be different just because of age. And then we modeled chronological age, using our glycans, and we can guess, somebody’s chronological age, with an average error of nine years using like, and we did it further, when we did it first time, it was actually very interesting. We were thinking about the forensic applications, that we could identify how old was the person who left the drop of blood on a crime scene, because I also have a forensic lab. So this was an interesting application. But then DNA methylation came in which was way more accurate for the chronological age. So Steve’s epigenetic clock, Steve Hormats epigenetic clock can guess an epic, chronological age plus or minus a year or two in a population cohort. And then we realize, actually, this is not fun. If you can accurately guess the chronological age, where is the valuable information there because I know my age, I don’t need a molecule which will tell me my chronological age. And then we learned that the difference between the glycan age and the chronological age is actually in by large determined with a lifestyle. So people living a healthy lifestyle will have a lower glycan age, people having unhealthy lifestyle will have it higher. Also disease, people with different diseases will have a higher glycan age than healthy people. Steve also realized the same issue and then he developed the green clock. And now there are many other epigenetic clocks, which are not tuned for chronological age, because that’s not fun, but trying to give some kind of biological information. And I like epigenetic clocks that are great. The only problem with them is that each of them is measuring something differently. And also, with all the companies selling the the epigenetic clocks, each of them is all different. They all call them epigenetic clocks, but they measure different CPG marks. So we will have to actually perform independent research for each of these clocks to know what they actually measure. So for glycans, since we started from the opposite direction, we know that high glycan age means more chronic inflammation. And these molecules are actually functional effectors of inflammation. So if you give immunoglobulins with these glycans, Which suppress inflammation, they will suppress inflammation, they can be used as a cure to heal people who have too much inflammation. So once we measure glycans in a person, and if we see bad glycans, we have no problems in telling the person No, you have bad molecules, which are doing damage to your body, maybe you can try to change something. And then if we see more and more good glycans appearing, we can say, you know, this is definitely helping you.

But for epigenetics, we don’t really know what each of the sites is doing. So epigenetic information, and as time is progressing, we’ll have more and more knowledge about it. And it will be much more useful. And I’m actually pretty certain that if we look properly at epigenetics, we’ll high find a proxy for the glycan age and epigenetics. And actually, this is something that we are now working together with Steve Horvath to compare, like regulation and methylation in the same people. But at the moment, I think this glycans give more actionable information. And the second big difference is that one of the disadvantages of epigenetic clock so far was that they poorly react to interventions, there are only few papers showing that if you do very aggressive therapy, epigenetic clock changes a bit. To the contrary, we are seeing glycans changing a lot with relatively simple interventions like weight loss, people losing weight, or improving their glycans, they’ve been gaining weight of their black glycans going in the right direction.

Robert Lufkin MD 31:52
What are the most? Well, yeah, to emphasize your point? Yeah, it seems clear that beyond the first generation, forensic type, chronological age, methylation clocks, we’re now seeing specialized ones, and it depends on what they’re trained on, like Morgan Levine is showing that you can really train them on anything and, and depending on what you train them on, that’s what they will be most sensitive to. So what you’re saying with, with glide, can clocks there, they’re at least the ones for the itG that you’re using are predisposed to inflammation, but inflammation is at the basis of all all our diseases. So it’s it’s very, very useful things there. So which interventions have you seen, that are most effective at reversing or increasing the glycan age that you’ve calculated though,

Gordan Lauc PhD 32:54
here, we have something which is anecdotal evidence, and then you have a few people 50 100, who do something and then we see a change. And then there are some proper studies, which we have done. So anecdotally, we collaborate a lot with one anti aging physician in New York with his video age, platform, and most of his patients will become 20 to 30 years younger after approximately a year in a practice. And I think the most the strongest thing he’s giving to them are hormones. He called it hormonal optimization. And definitely in the woman around perimenopause. Estrogen is a big issue. Once they went woman start to lose estrogen. Their glycan age goes up drastically. And for men, it’s also estrogen. But in men, estrogen is generated from the foster on with enzyme called called aromatase. And we here we did one proper, placebo controlled randomized trial, where we had a group of both men and women were the in woman menopause, and also in what is called agile pose, probably, hormonal hormones were blocked chemical. So you have a young woman, and you block the production of hormones. And then there was treatment group, where they were receiving estrogen supplementation and placebo, where they were not receiving anything. They were just given a patch, but it was a placebo patch. And we saw that in a placebo group, woman on average aged nine years and six months. While estrogen group, this did not happen. So women who were given estrogen back were protected from this accelerated aging. And we see it often in women in the perimenopause that somebody who has for example, a very good Black can age before Would age in like 2030 years in a year? Well, once given hormone replacement therapy, this goes down again, in men, testosterone works unless you block aromatase if you block aromatase inhibitors of aromatase because people when give when they give testosterone to men, they want to see very high testosterone and then the toaster on usually being lost to estrogen. And this is why some people give this supplement a this blocker of aromatase to keep the first turn high. But actually, this higher estrogen is what also protects men from these bed pro inflammatory lichens. So definitely one thing which works with hormones,

Robert Lufkin MD 35:53
it’s interesting because of the the ATP results for the interventions testing program, which is where mice are given certain drugs and then they actually measure the longevity in the mice to how long they live and only a few drugs have been positive things like rapid mice and have been effective in lifespan extension. But one of the one of the the other drugs is 17 Alpha Astra dial, which at least in men, it it in, it’s not it doesn’t produce sex characteristics, but it it’s again, related to estrogen.

Gordan Lauc PhD 36:29
And I know that study, so we have problems with working with mice, we have one study where we compared I think close to 100 different strains of mice. And there are so different because you know, all the mice which we have in a lab are actually immunological imbeciles, they they have lost most of the immune processes, because the only thing they need to do is to eat and make little mice, they don’t have all the challenges which normal mice in the wild has. So mice are not such a good model for this glycan aging, at least Well, some strains of mice are, but main laboratory mice are not as good. And yes, estrogen is very important. And something which is maybe simpler and maybe more acceptable to majority of people is also weight loss. We have very strong data showing that if you lose weight, your glycans improve. For example, we had several cohorts of people on bariatric surgery. So they had this summer production, they lose 10 2030 kilos. And we will have one client who improved for 37 years in the half a year. So not everybody improved so much, but weight was helps. But again, bariatric surgery is quite radical. So we were wondering whether just the regular weight loss is also helping. And we had a study on 2000 twins, which were analyzed three times over 15 years, cut three samples over 15 years. And we have seen there that twins who are gaining weight over time, were aging faster speeds on gleichen. Clock, and then twins who were losing weight. Now also we have some people who went into different programs and losing weight. Generally, we just like an edge with one exception. If you’re exercising too much. If you’re overtraining to lose weight, then you’re also increasing inflammation. So it’s not good on the glycan age test, so too much exercise is not good.

Robert Lufkin MD 38:51
Yes, you were seeing exact heard anecdotal reports about athletes doing biological clocks, and they may find their age is elevated when you think they’re, you know, Healthy Athletes, they would be younger,

Gordan Lauc PhD 39:05
but not not not all anecdotal. We have several studies properly designed studies, which we did, where we see that if people overtrain they actually get worse. And we also have one proper study where we did this high intensity interval training where they immediately improved. So I think training is important, but the relaxation is equally important. And although you know our well I think this was actually brainwash in the last 30 years by the food industry, where to avoid scrutiny of the processed food. They were forced forcing, they’re kind of supporting researchers to study exercise and then the, the, the mantra was you just have to sweat it out. You know, you have to exercise more and then you can eat all this junk food, which we are selling you, and now we actually know, these two things don’t compensate. So you cannot sweat out the junk food, you have to stop eating the junk food. And then you have to exercise moderately, and this is fine. And it’s so logical because you know, professional athletes, they’re old in their 30s. They’re weird out because they exercise all the time, we don’t have bodies, which can work all the time, we have to exercise, give this stress give the signal for muscles to build up for everything, which happens when you exercise. But then we have to relax and allow our body to fix all these small damages which happened.

Robert Lufkin MD 40:43
Now, now we have a we have a a glycosylation clock now that that measures different, different aspects of our lives, but it strongly influenced by inflammation. And we’ve shown that lifestyle and other interventions can reverse or or dial back the the age on that clock. Now that I guess the final question is, What evidence do we have? Or do we know that reversing the age on a glide can clock shows any benefit? Is it is it beneficial and sort of like I may have wrinkles in my forehead, and that’s a marker for aging. But if I take Botox and inject them, sorry for this analogy, I live in Los Angeles, so we see a lot. But if I inject here, then the wrinkles go away. So that biomarker for aging, I look younger, but really none of the fundamental processes have changed and sort of an epi phenomena that so I guess the question anytime we have clocks that we rewind, the next question is, do we know that rewinding improves longevity or decreased risk of disease? Or is it just too soon to tell?

Gordan Lauc PhD 42:00
So we have one very nice elegant study, which we did together with a field show from the University of Texas Southwestern where he has a line of evidence suggesting that these bad ag license, which are like the final salic acid are actually causing hypertension. So he did a series of studies on mice, where if you put mice on a high fat diet, they become obese, and they develop hypertension, and their glycans become old. And there is a dietary supplement called the annissa, dominos amine or manak. If you give it to mice, who are on a high fat diet, they become obese. But their immunoglobulin glycans stay young. And mice who were on a on a high fat diet developed hypertension, while mice who were supplemented with the minosa mean, they did not develop hypertension. So actually, this mannose amine, which is the sugar, but sugar, which is causing this good type of IGA glycosylation prevented mice for developing hypertension. And this was publicly published in circulation, which is the best cardiovascular journal. And we joined that study by looking at 1000s of people. We didn’t do intervention study insurance. But we have shown correlation that people with higher blood pressure will have less of these good glycans. And very recently, on a couple of weeks ago, we published another paper showing these bad glycans today predict hypertension in the future. So of course, we still have to do a lot of research, there is definitely not something like FDA approved claim that if you approve, improve your ag glycans, you will have lower risk of cardiovascular events. But there is a lot of cross sectional data, suggesting that actually improving your glycans will improve your chances of not developing diseases. And of course, there is this entire line of evidence showing that inflammation is a predisposing factor for disease. And we know that these glycans are suppressing inflammation. So I think we can be pretty confident in claiming that if you improve your glycans, you are suppressing inflammation. And if you’re suppressing inflammation, you’re reducing the risk of cardio metabolic diseases. So I think it’s pretty safe to claim that improving your glycogen age is decreasing your risk of diseases, although, of course, we cannot make this type of claim because we don’t have an FDA approval for that.

Robert Lufkin MD 44:51
Yes, yes. It’s an exciting time in this, this this whole space and it’ll be fascinating to see what comes down the line as far as diagnostic testing and as we understand these better knowing what you know, as a as a world authority or the world authority on glycans and and this this space of longevity and, and health, I would be curious if you would share with our audience how this knowledge is informed the personal choices that you make as far as your lifestyle and an exercise instead of going what, you know, what do you do?

Gordan Lauc PhD 45:30
So that’s a tough story. So, I think, six or seven years ago, I learned that my glycan age is horrible. So currently, I’m 51, Roger Collie, my glycan age is 78, which is really horrible. So first year, I decided, Okay, I’m just too fat, I have to lose weight. So I spent the entire summer hiking in the mountains, three, four hours a day, 2025 kilometers hiking over the mountains. And I did not improve much. Because what happened, I did lose weight. I felt better. But I was overtraining, I had so much pain everywhere in my life in my feet, I was just doing too much exercise. And then I kind of gave up before training. And then I was testing different things, including that I also discovered that I have this obstructive sleep apnea. So I have this simple now, which is making me sleep much better, which also improved my glycan age a bit. And something which was also scary for me, maybe three years after I had very high glycan age, I also develop hypertension. So I just went for regular checkup, and my blood pressure was all all the way through the roof, something like 200 over 110. So I had an early warning, which did not help much. Besides that, I went for this checkup and discovered high potential which I now control with the bills. And definitely I use this glycan age to motivate myself not to eat too much. Because I know when I gain extra 10 kilos, my glycan age goes up, I started losing kilos, make like an inch go down. But I think my primary problem is my lifestyle. I work too much too hectic, it’s crazy. I have a lab of 50 people, I work at university, have five kids and a dog. So it’s, it’s you know, it’s it’s a lifestyle, which, which it’s kind of killing me. But I know, and I’m trying to improve, I’m always comforting myself that it would be worse, if I would not be trying to improve. So we’ll see. Maybe I wait for a little bit more research to be done with this colleague from New York. And maybe when when I see which of his everything he’s giving to his patients actually working, maybe I will also try that out.

Robert Lufkin MD 48:13
It sounds sounds good. Keep us posted. Definitely. And Gordon, how can people get in touch with you? Or, sir? or How can they follow you on on social media and see what you’re doing? Is there any website we could point them to?

Gordan Lauc PhD 48:28
So there is the glycan age.com, which is a sales point for the glycan age, it’s being sold globally, so anybody can can buy it. I’m pretty active on Twitter and LinkedIn. I’m the only person with my name so just googling me on this social network sign. I also post a lot of on Facebook, but this is a mostly I do it on Croatian language in my home country. So this is not interesting for people outside so I think twitter twitter is probably Twitter and LinkedIn are the best places to see where they always post everything new what we do as a research on these two networks. Great, well,

Robert Lufkin MD 49:09
thank you so much for spending spending an hour with us today and and helping us understand glycans and the fascinating world they are at certainly opened up my mind and and I can’t wait to follow the work you’re doing and see all the new developments in the future. But thank you so much for being on the program.

Gordan Lauc PhD 49:30
So thank you for your invitation. One final note is that we are extremely interested in doing research and learning something new. So if there anybody is doing an interesting study, any kind of intervention, trying to help people we’re interested talking to bikers,

Robert Lufkin MD 49:49
right and and please add our audience reach reach out to Gordon if you have any interest in that area. If for if you’re on the scientific investigation side, that would be great. So thanks again, Gordon and look forward. Hope this is the first of many conversations we have.

Gordan Lauc PhD 50:07
Thank you It will be my pleasure.

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