Can Diet Reset Epigenetic DNA Methylation Clocks?
Today we learn how diet, genetics, and epigenetics interact with each other to impact our health and longevity, and how to use this information to design personalized lifestyle interventions from a true expert in the field.
Dr. Lucia Aronica received her PhD from the University of Vienna and has research experience from the University of Oxford, University of Southern California, and University Federico II of Naples. She is also Lecturer at the Stanford Prevention and Research Center, Genomics Lead at Metagenics Inc., and editor of the peer-reviewed journal Life by MDPI.
Take away points:
-We get our genetic information from our ancestors while epigenetic information is from our life experiences
-Epigenetic change can occur via three mechanisms: 1- small RNA, 2-histone modification, and 3-DNA Methylation
-DNA Methylation is currently the best epigenetic modification for detailed epigenetic analysis
-First generation DNA methylation clocks (Horvath et al) were chronological clocks, while second generation clocks (GrimAge, etc) tend to be biological clocks trained on specific conditions/phenotype
-Chronological clocks are useful in forensic applications
-Chronological age can deviate from biological age reflecting varying risk for outcomes
-Athletes showing increased biological age may be related to short term inflammatory genes and cytokines for the adaptive stress response to exercise
-In Ketogenic diets can see down regulation of excitatory brain pathways as possible mechanism for effects in epilepsy population
-Induced pleuripotent stem cells can be produced by transcription factors that reverse epigenetic age
-Biologic DNA methylation clocks are very valuable for lifestyle intervention and longevity research
Gardner CD, Kiazand A, Alhassan S, Kim S, Stafford RS, Balise RR, Kraemer HC, King AC. Comparison of the Atkins, Zone, Ornish, and LEARN diets for change in weight and related risk factors among overweight premenopausal women: the A TO Z Weight Loss Study: a randomized trial. JAMA. 2007 Mar 7;297(9):969-77. doi: 10.1001/jama.297.9.969. Erratum in: JAMA. 2007 Jul 11;298(2):178. PMID: 17341711.
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Robert Lufkin 0:01
Welcome back to the health longevity secrets show with Dr. Robert Lufkin. Today we learn how diet, genetics and epigenetics interact with each other to impact our health and longevity, and how to use this information to design personalized lifestyle interventions. Dr. Lucia ronica received her PhD from the University of Vienna and has research experience from the University of Oxford, University of Southern California and the university frederico, the second of Naples. He is a lecturer at the Stanford prevention and Research Center. She is the genomics lead at meta genetics, Inc, and is the editor of the pure peer reviewed journal life by mdpi. Before I begin, I would also like to mention that this show is separate from my teaching and research roles at the Medical School, which which I’m currently affiliated. It is, however, part of my continuing efforts to bring quality evidence based information about health and longevity to the general public. Now, enjoy this interview with Lucia urraca. Dr. Lucia ronica. Welcome to Health longevity secrets.
Lucia Aronica 1:18
Thank you for having me, Rob. It’s my pleasure.
Robert Lufkin 1:21
It’s so great to have you on the show. And before we dive into the fascinating work that you’re doing, maybe you could tell us first a little bit about how you came to be so interested in this field?
Lucia Aronica 1:37
Yes, so I’ve been in the field of epigenetics for more than 15 years. At the beginning, I became interested in, in genomics in general. And that’s because in the year 2000, when I started my master’s studies, the human human genome was sequenced. And I thought that was an opportunity for the whole field of, of medicine to uncover new secrets about our biology. And now we can use these secrets to help people live a healthier, longer life. And so I started I I’m actually I switched careers, very early in life, because I did. I studied the ancient Greek is late in literature, poetry during my high school, there is a high school called detail classical in Italy, where I’m from, and I was in love just with humanities and monistic studies, I never thought I would venture into science. And, but that event, I am also acutus animals, so I thought, perhaps I will give it a try, let’s venture into something new. And I will never regret that it’s, it’s been a lovely journey. So I first became interested in in the field of genomics. And then after completing my master’s studies, eataly Naples, I moved to Vienna, where I again, ventured in a new field of genomics, epi genetics. And, and I started to, to work on one of the many epigenetic modifications at that time it was a small RNAs. And probably your your audience is aware of what a B genetic is Berger,
Robert Lufkin 3:50
you could take a moment if you don’t mind, and differentiate you Nomex versus epigenetics and also the three modification, three main modifications in epigenetics would be great.
Lucia Aronica 4:02
Yes, happy to do that, because I was so lucky to be able to work on each of those three modifications. So let’s break it down and make the complex easy to understand. So, genetics, describes refers particularly to the sequence of the DNA inside ourselves, that provides instructions to make the protein they make up our cells and, and those who produce enzymes that catalyze important biochemical reactions in our body. And, and then at the Greek prefix epi means on the top. So on the top of our genes, we can find the molecular tags called 80, genetic marks that that modulate the activity of those genes, meaning whether they’re turning turned on or off. And, and this has remarkable consequences in the way we look and perform at the, at the cell level, and also the system level. So the entire organism, for example, we have the same DNA, the same genetics in every single cell of our body. And yet, we can see that the cell of my hair look different from the cell of my eyes. And the reasons for that is that is that my hair cells have different genetics. So they are using some genes turning on some genes, and turning off some other genes, whereas different genes are turned on or off in my eyes. And so this is one of the main examples of how it the genetics can modify the expression of genotype the genetics into phenotypes we can perform. And, and, and, and, and so that’s, of course, a fascinating field. And that’s, it has also many implications in, in health and disease. And we understand now that most of of the diseases we know are actually in a genetic component rather than genetic one. And even things like improving health after an a lifestyle intervention, we are not going to change our genetics after initiating a new diet or a new training program, what happens is that many genes are turned on or off, and those genes are responsible of the good effects of building muscles of losing weight that we see when we go on a lifestyle intervention. So the epigenetics is basically the another phase of genetics, the flexible side of genetics that allows the environment or our lifestyle to be turned into biology and and affect Yes, the way we we will look performing whether we are sick or healthy. So I was I was very excited to be so lucky to start my PhD in 2006, when the Nobel Prize for RNA interference was awarded. So RNA interference is one of the many mechanisms of epigenetics. So epigenetics modifications include small RNAs that mediate this phenomenon of RNA interference, and then their histone modifications and DNA methylation. So in order to understand these three modifications, let’s first understand how genetic works at the molecular level. So
genes can be turned on or off by opening or closing the chromatin. The chromatin is the the DNA plus histones histones are protein that are positively charged and help DNA become very compact in our cells. The DNA is negatively charged, the history positively charged the complex together into chromatin they mix the chromosomes. And so this makes the DNA very compact within a couldn’t fit in ourselves is more than two meter long six feet and it is fitting the nucleus which is very small, a few microns is like fit in a 20 kilometre long string into a ping pong ball. So, histone sand, and again they are are compacted in a set of markers, but in this way, we can’t read the genes. We can’t use the genes the genes are off. So in order to to Turner genes all you need to open that. And that’s the job of epigenetic modifications. So, some modifications are modifications on the histones, right? So you can you can modify the histones with different PJ BJT modifications make elation is very common is very popular, but there are so many other modifications there is acetylation for for phosphorylation of distance. And when you modify the response, you change the electric charge of the instance. And so the you can affect the way the DNA is complex, these Huawei on the other side, this is some modifications also act as a flat flag that recruits other proteins in the cells machineries that can open and close the chromatin. So it’s it’s the they work with many functions on one on one hand, they modified modified the electric charge around the DNA on the other hand, they recruit protein. So, these are histone modifications modifications of the histones and then there is DNA methylation, which is the methylation so it’s only the modification is a methyl group ch three that is is added to the DNA itself, and specifically to cytosines one of the letters of the DNA that are located within si g dinucleotides in our DNA, and these are called si p g sites, P stands for the phosphoryl group between the two nucleotides. So, we are we are going to some jargon, but it will be useful in to understand and what we are going to address later RNA that are complicated, I will not go into detail. I started my PhD like that and are fascinating. But why small RNAs are fast fascinating. Because there are sort of more by epigenetic modifications they target. They help target either histone modifications or DNA methylation where they need to be in the right place at the right time. And because why they’re mobile, because small RNAs are synthesizing the nucleus and then shattered in this in the in the cytoplasm. And during my PhD, I was characterizing how these small RNAs works in tetrahymena thermophila, which is a properties that became family sexually because the pen of Marys and telomeres, so working on pyramids was first characterized in that the diametre mafia is a beautiful modern system to work to study epigenetics.
Robert Lufkin 13:13
So, so this is fascinating. So it’s almost as if the, is it correct to say that genetics, we is the information that we got from our parents and our ancestors, whereas the epigenetics is experience that is a result of our lifetime experiences, and our lifestyle choices and all things that happen to us in our Live Set a correct way of looking at it, it’s correct
Lucia Aronica 13:39
and beautiful for me, it’s, we know, he intuitively know that we are what we do. We are what we eat, and we are worth what we do. But now with the field of epigenetics shows that actually, this this information, becomes biology. And the genes can learn from this information, remember, and store good memories and bad memories of what we do.
Robert Lufkin 14:14
And it seems like you have a unique experience in that you’ve worked both with a small RNA at one point in your career, and then you work with histone modification. I think after that
Lucia Aronica 14:24
I PhD Yes, yeah. And now I’m, I was I went, I was studying that I moved to Oxford, England, and I was studying the role of Eastern modifications in DNA damage and cancer. There is actually a link of how our DNA between genetics and epigenetics in many levels, and one of these is that when our DNA gets damaged, which is associated with cancer, these are facts of our genetics. And on the other hand, if we have some problems with epigenetics, This makes us more prone to have DNA damage. And David Sinclair is also is Miss doing some work on this link, which I think it’s very exciting. And I identify that the time one gene in working with East cells, that actually this gene that we also have these genes, and these mediating this connection in the in, in these cells, and this gene is mutated in many cancers in human. And then finally, I, I, now I’m studying DNA methylation, the third modification as Stanford, finally, being able to marry my interest for Molecular Biology and epigenetics. My interest for lifestyle medicine, I myself, has not I am I, during my PhD, I also did an experiment in my own kitchen. So being an Italian, I was born and raised, eating a typical Italian diet made of the three piece pasta pizza in panic, which means bread. And so I was, and I was actually feeling facts that I felt effects, because I think this is a little common, especially among women who want to be lean. So I was overall healthy. But as I mentioned, I’m also very curious. So when I, when I started my PhD, I tried to, to switch and change diet because I read a book, a book by Gary Taubes good calories, bad calories. And this book was an in depth review of the science of fats and carbohydrates. And the book was arguing that actually, eating a higher fat diet with healthy fat and lowering your current virus may help you improve your blood lipids and metabolism. Anyway, I tried that. I was just eased when I took my first blood blood test after two, three months of being on a diet. So my triglycerides went down threefold, and my HDL went up three fold. And for me, it was, I was just curious to understand why. And this was in 2007, when Professor Christopher Gardner, a Stanford University had published a study in 250 women showing the same thing. These women were randomized to different diets with with different content of carbohydrates and fats. The study was the A to Z study, because they tested force for four diets, from the Atkins to the Learn and zone. Anyway.
I, when I was doing this experiment in my own kitchen, I realized that there was a study in men in Stanford showing the same benefits of a high, high fat, low carb diet in women. And I had this dream to look at what happens at the key genetics when you go on a low carbohydrate diet. And, and so I when I was finishing my postdoc in Oxford, I remember the night it was late, and I’m I, I must confess, this is my weakest link. I am up late at night. But sometimes that’s useful, because that night, I decided to write an email to Professor Christopher Gardner, and just spontaneously tell him Look, I know that you’re planning the follow up study to the A to D study, called the diet fit studies. And so he was planning to do a bigger study in men and women with 600 people. And I wrote him that I would love to join the group and look at making genetics of, of people and specifically the DNA methylation. Why I proposed the regulation because we have an accurate test to measure the methylation at the single nucleotide level. So the elimination is the best modification to start if you want to measure a difference between for example, pre and post diet, whereas estimating vacations are not very quantitative. So I, I did I made this proposal and when I woke up the next day, I Christopher told me, yes, join our group. can I contact your referees? And I was like, wow. Aye, Aye Aye. Didn’t expect that. And so, for me, it was a big life changing event because I had been eight years in Austria at that time, I was loving living there. I had learned the language, I can speak German, I was also I was attached to today, but but but sometimes in life, you you have to shake it up. So this was actually a friend of mine told me and and then I yes, so now I’m, I’m looking at DNA methylation, before and after a lifestyle intervention, specifically, a low carb or low fat diet that the participants of the new study the diet fit study by Professor Christopher Gardner are following for one year. And the trial has been already completed. But there are many groups system for looking at different data’s microbiome omics, metabolomics, and I am so lucky to lead the the epigenetic analysis and also some genetic analysis coming next.
Robert Lufkin 21:37
Oh, that’s so exciting, exciting, the, the the low fat and low carb diet, how, how low? Is it on either side? Or what? What? What are they going for with those?
Lucia Aronica 21:52
Yeah, the study design of the dyfi studies uni. So is a, you know, there was a lien bought face, initial Limbo phase called the limbo, because people were encouraged to go as low as they could with carbohydrates, or fat, the target was 20 grams of carbohydrates, or for the low carb group, and 20 grams of fat of fat for the low fat group. And of course, is a very hard target to reach. Right? So most people deviated from that. But this was by design, because then, after three months, people were encouraged to titrate back carbs or fats up to a level that was considered sustainable for life. And that study got many critics For this reason, because many people have fought in the in the low carb or low fat space felt, why did you encourage people to titrate back in this way, you? You miss you missed potential benefits of either diets. And I agree with that, I’ll just comment and reply. I know why Christopher designed the study like the like that. And is because it’s there is always a trade off to making done that is more impactful for public health. Something that is more likely, you know, for the diet is more likely most people will actually do in real life. And this was the dyfi study, or a study that is more targeted to answer the scientific question is low carb or low fat, bad, better for these outcomes. And, of course, being a molecular biologist, I would prefer to force people to eat just 20 grams of carbohydrates, or fat for one year, that hot that will make me the happiest, because I can measure better and stronger signals. So no question. So I, I get it, I get it. But I also understand, you know, the other perspective and, and so I really appreciate the opportunity to I’ve learned all these difficult facets of clinical research is not the simple. So I come from a background of being a molecular biologist, and being able to isolate factors. So at the beginning, I thought, Okay, this is going to be complicated, but that’s the beauty of self clinical research.
Robert Lufkin 24:54
Yeah, at least you’re able to do it in humans and you kind of get what you get What? What methylation signals? Are you going to be looking at with your with the DNA methylation? Are you going to be using standard clocks? or ones that you look at yourself? And maybe maybe back up a little bit? And just, if you could introduce our audience or refresh our audience on DNA methylation clocks?
Lucia Aronica 25:21
Okay. Yes, sure, I, I will, first describe the different projects we are doing. And I’m happy actually to have the opportunity to talk about that, because in this way, perhaps I can, some listeners that want to collaborate on this data sets can reach out to me, because I already did many analysis, so we already have a ton of working genetic data. So there are different pros. I’m doing the first, that we already have data, it’s about just comparing the DNA methylation before and after the diet on the two different diets. And we see remarkable difference. So the genes that are turned on in on the low carb diet, or low fat diet are completely different from each other, there is a little overlap. There are some usual suspects. For example, we see that on the low carb diet, enzymes that are required for for for fat breakdown are turned down because there is more fat, and also different pathways that are turned on or off in the in the different diets. For example, low carb, there is actually the gap regulation of some immune pathways, especially related to natural killer cells. The pathways, and then on the low fat diet, there are some cancer protective genes that were turned on, especially regarding to colon cancer. Anyway, these are just examples. So there is the DNA methylation analysis, just comparing the two diets and understanding which genes are turned on or off. And this is an important part of clinical epigenetics, because for example, you might you may prescribe dietary intervention is upregulated some genes more than another depending on your outcome. One example is also We know, for example, the ketogenic diet is used sometimes to treat drug resistant epilepsy. And from an even genetic point of view, we see that on a ketogenic diet, there is an upregulation of hynny batory pathways in the brain, and downregulation of the excitatory pathways. So this is an example to say, okay, we know that this is happening behind the scenes of gene expression. And this makes sense. So it’s this is what the first project I’m working on, and then the second project and that and that we initiated that then was killed by COVID. And I hope that we can bring this back. So I’m happy to talk now, visually, and crystal, Christopher Gardner, and then Professor Steve bought back. So we connected together before COVID. Because Steve, Steve Horvath is the professor who developed the epigenetic clocks that I will explain now. And he, he developed in 2019, a new clock that was predicting, really biological age and mortality. And, and I connected with Steve and Christopher to test the this clock. This is called the dream age, because it’s a phrase clock in the diet fit study. We had the older plan made made these plans and we also involved the University of Vietnam Professor cutlines vagner. I will say hi to him, but anyway, we were we had this plan and then this is on the backlog, but I hope that we will also assume that plan. So what are epigenetic clocks. So because we have learned that our environment, our lifestyle can change our epigenetics.
And that and we can measure you name inflation, so many sites. It turns out that when we measure the DNA methylation 1000 sites in our genome We get a readout of the true age of our cells and tissues, which is called biological age and can deviate from our chronological age. So for example, we can be 40 years old, but then ever biological age that is 30 or 50. On biological ages measured by this, the level of DNA methylation at different sites in our genome, and there are many epigenetic clocks, that different differ from each other, depending on which sites they measure how many site sites and whether the algorithm that we’re used to train these, these clock clocks through machine learning, were trained against to predict by chronological age, so, or biological age, which is, for example, outcomes of phenotypes of aging, mortality, cancer, for example, or some blood lipids and markers that we know are associated with metabolic disease. So, usually the the blocks that were trained to predict biological chronological age or Kohaku are called first generation clocks, and the one that are trained to predict more phenotypes of aging and biological age are called second generation clocks. And the first generation clock that is more shows the highest correlation with chronological age is the Horvath clock 2015 and then there are a couple of second generation clocks like the phenol age by Morgan Levi and the green age by Professor Steve or that the one that we hope we are going to use. So, this second generation clocks might be better to, to look at before and after. So that the changing in in biological age before and after intervention, because this clock correlate with the market a change, like can be blood markers or phenotypic aging, whereas the chronological age clock, like of the first generation, like the horbach, clock doesn’t 13 might be better to for the prediction of forensic age. For example, for the forensic sample, for example, if you if we find if you find the DNA sample and you need to know how, how was the was the purse at that time and this this action was a legal case where I believe that determine the age of the person was important to determine the sentence because if that person was younger than 18 years old, so the the punish the penalty would have been different, right. So you know, in then for forensic purpose, you want to have a clock that prints better chronologically doesn’t change depending on whether the that person had the eggs or or or muffin for breakfast. arrived?
Robert Lufkin 34:00
Yeah, yeah. How did how did the DNA methylation clocks compare with you mentioned some other ones but the like the glycation clocks or the inflammation clocks, we are seeing more and more type of biological clocks coming is DNA methylation? It’s obviously your interest, is that going to be the most important one you think or are they looking at different things?
Lucia Aronica 34:27
These are very interesting question. So I also teach a class system for the called longing for longevity from biology to biohacking. And I I teach these topics together with Madalena Dorner. She’s the CEO of a company that is developing signal blockers for senescence cells, and that can be also another marker of aging. So for your questions, as you pointed out, biological age is Thinking nothing. So a biological age could be just a biological readout of living, right. So it encompasses many things. epigenetics is one of the clock that we use to measure biological age, there are molecular clocks like the one you are mentioning, it’s an epigenetic age or glycan age. Now, and there are there are telomere based clocks, and then the results in a new nature based on gene expression of our immune cells, and many more will come. But then there are functional clocks, based on simple blood markers, you can get your blood work done. And because many of these blood markers correlate with biological age, you can have a functional clock that many clinicians are actually starting to use in their, in the clinic and just estimate the biological age. And then that even BG color clocks like people have based on face recognition, of course, you know, there is a age of the skin that is visible. So this just to be met, the big picture biological age is, is a new concept that is used to define how the environment can affect the aging of our tissues and cells. But it’s a composite metric, because my skin may be older than my liver, if I like to some bait every day. But I have a healthy diet. Right. So and So to your point. There is not a bad, best clock, glide can age for example, I think it’s it will be very relevant as a signal of probably more glucose metabolism problem, right? There are different signals of aging. And for example, one, I think one interesting and future directions that biological clock should address is that I’ve and this is only anecdotal, but there are many athletes that complain that they are when they take an epigenetic clock measurement, they will call that and they are and yet they are, you know, supposed to do the right things. And I would love to test this hypothesis. I I don’t know why. But it can be that training, we know exercise does cause many genetic changes. And, and some of them are actually the return on inflammatory genes in the short term, and cytokines. And these inflammatory genes and cytokines are important to mediate the adaptive response to exercise. And it’s actually good for us that the end, buyer activating distress pathways, our cells become stronger. And so it could also be that the epigenetic clocks are capturing that inflammation signal. I’m not, I’m just saying, you know, that that we will need to understand which signals are captured by which clock and so that we really can say, can more than say we are stating biological age, estimating these components of biological age is more relevant for you.
Robert Lufkin 38:55
Yeah, yeah. So, so following up on that, now that we see biological clocks and DNA methylation clocks, investigators are starting to see how lifestyle can affect the clocks like you’re doing and also I think Kara Fitzgerald just published a nice study on that where where they showed a reversal of biological age at least by one one clock, I think it was the four of us clock then the question becomes what evidence do we have that reversing biological age is manifested through a biological clock affects outcome and survival? I mean, is it just like getting a Botox injection and they’ll make you look younger, but it doesn’t really change your your outcome necessarily. I I guess we have David Sinclair’s work with the with the mice in the Yamanaka factors with osaa winding back supposedly, the epi genetics on those to decrease age related vision in his science paper this year. So, is that valid? Do you think? Or do you know any other evidence of that?
Lucia Aronica 40:12
Yeah. So this is an important question. I know we don’t have answer sexually even civil war is, is cautious about, you know, the actually, but is the clinical utility on our agenda clocks? I think that we establish that utility, we need more studies like the ones by Kara Fitzgerald. So you mentioned she, she’s a colleague and that she he demonstrated that after a lifestyle intervention, there was a reversal of biological age and some relevant clinical improvement and clinical outcomes, right. So then we can start to, to to demonstrate that there is a an association between actually improving clinical outcomes and in biological age, and the more we build designing dance, the more we can also use biological age as a surrogate marker for for aging, which is very useful, because in that, in that we can’t run interventions for years to wait that people are, are getting older. And for the second question that you you were asking them about the experiments done by David Sinclair, with the epigenetic reprogramming. And just to give a refresher to your audience, we can actually reprogram cells to differentiate from, for example, hair cells to embryonic stem cells, embryonic stem cells, so is ipsc is actually is induced pluripotent stem cells ipsc can become any type of cells because they don’t have the genetic marks to his truck, the jeans on or which jeans should be turned on or off. So they have a ton of potential. So these NP genetic process and we can add a cocktail of of transcription factor that reversed a cell into our PCs, and then this cell can become any type of cell. And there is evidence that when we do that, the residual juhani the biological clock goes back for most clocks. Actually, not all the one with any way this is configured, but most clock goes back. And, and very Sinclair even showed that in vivo in mice, when you transiently treat the optic nerve cells that have minds that optic nerve damage with this transcription factor, they’re called Yamanaka factors that reprogram the genome, then you have actually an epigenetic rejuvenation. So this is the first step to the to show these but we don’t know what these will play out in, in humans, right, for which outcomes because these were either h mice or mice with a with an optic nerve damage. So to get back to your question, I think we still there is a term to do to make biological injury, you know, clinically useful, but in the meantime, I think, including disc clocks in lifestyle intervention, can interventions can first of all help this research. Further, so I encourage all the conditions to do that, and then can help us understand which mechanisms of aging are more relevant for which the desired outcome of for lifestyle intervention so and it’s exciting also for the participants, I am collaborating with some doctors, for example, that are testing biological age while they’re prescribing an intermittent fasting intervention and I am editing a special topic for frontier genetics with Morgan Levi and the tourism bus. Deanna Stanford University. Aging clocks in longevity medicine. I mentioned this because I’m sure the reader medications and scientists in your audience and we will love. We will love to get your submission. I think that the topic is running for other six months. So don’t wait too long.
Robert Lufkin 45:32
Or great. Would you like us to put your email in the in the show notes too for them to contact you? Yes. Is that okay? Well, have your website also on there?
Lucia Aronica 45:42
Yes. Yeah. And
Robert Lufkin 45:46
yeah, if you’re looking for collaborators, in addition to scientific collaborators, are you looking for patient or lay people, participant collaborators also are mainly right now just scientific collaborators.
Lucia Aronica 45:59
For, for now, just scientific collaborators, just because we probably went once we have, you know, a new study, then, then Yes, I will. Yes, I will let you know. And if you can help me, perhaps recruit people, for now we have a ton of data. And we have the luxury of sitting on on a goldmine and having too many things to do. So we found a collaborator at Imperial College London recently to look at some of the genetic data and with metabolomics. But just Yes, we have we have done whole genome bias or fixed sequencing on the biggest losers from the study. And then we are we are also looking at some genetic biomarkers of diabetes. And whether they change after the intervention, we have the data, just like prioritizing which project goes first is difficult, because in the meantime, there are all sorts of studies that we are working on. For example, testing a keto Jane diet, and comparing that with with a low carb Mediterranean diet. So of course, there are too many projects to work on. And I also need to teach. If you also I have some collaborators that can clone me. Very useful thing to know, that’s
Robert Lufkin 47:31
so exciting, so many, so many fascinating projects in it in the last couple of minutes. Maybe you could tell us with your with your knowledge of epi genetics and genomics and high fat, high carb, low fat, low carb diets. What what lifestyle choices have you made in your own life as far as diet or exercise or supplements and those sorts of things?
Lucia Aronica 47:55
Yes, I am happy to share that. And I think I already shared that the first part of the story. So I think the biggest change was trying the low carb diet. And since then, I never went back. So it’s more than now more than 10 years, 13 years. For a low carb diet. There are many ways of doing low carb diets, right. But I just mean really eating whole foods. And these pieces already low carb because if you’re eliminating the refined carbohydrates, pasta, bread pizza, and we find out while you are doing a low carb diet. So and I think this is a common ground and everyone everyone can agree on that whether you are vegan, plant based or, and this is already low carb, and I think this is the big the biggest improvement people can see in their in their diet. I’m also in within low carb, I’m choosing more low carb vegetables. So that are those that usually grow above ground. And the reason for that is that they tend to be more nutrient dense compared to the calories and more Ricci fibers than for example tubers. So and, and then protein from a variety of sources of the vegetables, the of course and fish eggs. I prefer a fish to meat I have a little meat just because I was born and raised in Saudi Italy. So I it’s it’s my taste. It’s a preference and then and I think that this is also important. There is not one way for example, I am actually in ketosis and they but then never track myself I I measured my ketones a couple of times while I was teaching the class at Stanford on a DR Jain diet and I was in ketosis. But there was not even trying to do that. And this is not a standard keto diet like the one they prescribe you eat butter, meat, nothing of that, right? It just eating vegetables, local vegetables, fish, or olive oil, avocado. And it’s, this is important, because there are many ways of doing a diet that are wrong ways of doing any diet, a keto diet, a vegan diet, there are wrong ways of doing all those diets. So I don’t like polarization, this is good or This is bad. It depends. There are many ways to, to do that. So this is my first probably lifestyle habit, and I feel freedom, I don’t count calories, I don’t track anything. It’s for me a fourth lesson enjoyable to have this diet. So another message, I think is important is that what is sustainable, is also individual. my diet probably will not appeal for most people, but I truly enjoy it. And I will never change it. So telling this is unsustainable. And he I think he’s wrong. Because we are eliminating options for people, we are deciding upfront what what is sustainable for people, we want to give people options, we want don’t want to eliminate options for people so and then. The second is exercise. So I’m big on exercise, but even in that space, I’m I’m a minimalist, I do the most difficult exercise. But a few of I spend a little time on this exercise and that I build my exercise in my routine. For example, I do pull ups while I’m preparing my breakfast. And that’s one day and then the other day I do push ups and the combination why prepare dinner, and then other cup a couple of days. I go through Stanford gym, I love the gym. And I do things that I can do at home like deadlifts and squats and I love that but it’s really like two or three exercises. And I define myself as lazy a person because I don’t get much other activity right rather than that I don’t run I don’t go I would love to do that. But I only have so little time. So it’s so possible it’s possible you know, you don’t need I am I love taking care of my body and I enjoy the the food I eat and I think it’s possible for everybody.
Robert Lufkin 52:55
Yeah, any supplements that you’d like to share.
Lucia Aronica 52:59
Um, I do take vitamin D when I can’t be outside in the sun and sometimes for magnesium, I have also memories with the supplements that I take omega threes, magnesium, potassium, because I’m deficient and vitamin D as a staples. Most people are so deficient. On those minerals. I tested my potassium, so I know that it’s it’s a little low. And also I use it a bit for preventing stones and perhaps you can you can say something about that because my physician told me that. Yes, I ever found history. And potassium citrate seems to help also with that. So, but so far, I’ve been thinking this a long time and I feel great. And yeah, omega threes are, you know, I eat fish, but we just eat. So the ratio of omega six and omega threes should be balanced in our body and most of us eat too many omega sixes. I also though I don’t eat a process. Diet. And omega sixes are found in vegetable oils, which are prevalent in processed foods because they are cheap and processed food wants to make money on. But I also eat nuts. A lot of nuts and nuts are high in Omega sixes. So I’m trying to balance my omega six omega three fatty acids.
Robert Lufkin 54:50
Well, great. Well thank you so much for taking the time to talk with us today and I’m going to any information you send me about news Studies and desire for collaborators will share with, with all our audience here and keep them in the loop. But once again, thanks so much for all the sharing all the exciting work you’re doing. I don’t know how you how you choose between such such fascinating projects, but it was, it was wonderful to have you on the show, Lucia I really appreciate it.
Lucia Aronica 55:22
Thank you very much. Thank you for having me. And just I want to mention that I also have another passion sharing my lectures on on YouTube started recently. I just needed a signal from from people, if they like it, I will do more of that and sacrifice some weekends for that. But if not, I really just take my weekend off. So if you want to check out my YouTube channel and give me a like or subscription that’s appreciated. Thank
Robert Lufkin 55:53
you. Yeah, we’ll put the links to the YouTube channel in there and I’ve checked it out. They’re great, great presentations very worth that I highly recommend it. But thanks again lucea and look forward to chatting with you again on the show.
Lucia Aronica 56:08
Thank you. Thank you for letting me
Robert Lufkin 56:10
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