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What can queen bees teach us about epigenetics? And what do polyphenols, stress, and sunlight have in common? Hint: it has to do with longevity science. To mark our exciting paper on the Potential Reversal of Epigenetic Age Using a Diet and Lifestyle Intervention we are hosting a series of podcasts focused on the science of epigenetics and longevity, and kick things off with talented researcher and Stanford lecturer, Dr. Lucia Aronica. Dr. Aronica is a passionate advocate of lifestyle medicine and is currently leading the epigenetic analysis for the largest randomized clinical trial in the field of personalized nutrition on low carb vs. low fat diets. Fascinating work! With her rich international research experience in nutritional epigenetics, Dr. Aronica guides us through the mechanics of epigenetics and epigenetic aging, the importance of hormesis, and the powerful epigenetic language of lifestyle interventions, including epinutrients. Join me in this fascinating conversation and find out what you can do right now to optimize longevity. Listen, learn, share — leave us a comment – I’d love to know what you think! ~DrKF
Exploring Longevity Medicine and Epigenetic Aging with Dr. Lucia Aronica
What is longevity medicine and how can lifestyle interventions reverse epigenetic aging? In this episode of New Frontiers, we are joined by epigeneticist and lifestyle medicine aficionado Lucia Aronica, PhD for a deep dive into the world of longevity science. Dr. Aronica is a nutrigenomics lecturer at the Stanford Prevention and Research Center with international research experience focusing on how nutrition influences gene expression. She takes us through the mechanics of epigenetics, the types of epigenetic clocks and aging as well as key lifestyle interventions (including epinutrients) for optimal health and longevity. Tune in today to hear Dr. Aronica’s preliminary findings from the largest study ever undertaken in personalized nutrition on low carb vs. low fat diets.
In this episode of New Frontiers, learn about:
- DNA methylation
- Histone modification
- Low carb vs low fat diets & epigenetics
- Epigenetic aging & biological age
- Types of epigenetic clocks
- Epinutrients
- Stress and hormesis
- Lifestyle interventions for epigenetic modulation
Dr. Kara Fitzgerald: Hi, everybody. This is Dr. Kara Fitzgerald. I just wanted to say that my intention over the next handful of podcasts that I record is to have guests on to discuss epigenetics and the science of longevity. Why am I doing this? Well, (a) I really want to pull the branch down of understanding for all of us. It’s because as you may be aware of, we published a pretty exciting paper. One that I am just really, still, needing to pinch myself on. It’s called, Potential Reversal of Epigenetic Age Using a Diet and Lifestyle Intervention, a Pilot Randomized Clinical Trial. This was published in April 2021 in the journal, Aging. This was looking at an epigenetic clock, the response of an epigenetic clock to a diet and lifestyle program.
Now, since we’ve published this, it’s gotten a lot of attention. We’re making the program available to everybody. In fact, we’re recruiting now for a second larger study. We’re going to continue to study this. As we build out making this program available to everyone, I wanted to also concurrently educate those who are interested in the science of epigenetics, in the science of biogerontology and longevity. To that end, I will be bringing you, hopefully, some podcasts that you find quite interesting. If you’re interested, also, in participating in our future studies or accessing the digital program or the book that will be coming out, head over to my website, drkarafitzgerald.com or you can go right to youngeryouprogram.com. Both will give you direction on signing up to be informed and what we’re doing to further this research.
Welcome to New Frontiers in Functional Medicine where we are interviewing the best minds in functional medicine, and today is no exception. I am here with a friend and colleague, a woman who I’m absolutely just delighted to be able to connect with. Again, her name is Dr. Lucia Aronica. She is a lecturer at the Stanford Prevention and Research Center. She’s R&D lead on genomics at Metagenics. Her research and teaching focus is on how lifestyle can change gene expression through a process called epigenetics. She is very interested in how we can use this information to design personalized lifestyle interventions for optimal health and longevity. She’s an epigeneticist. Her background is in epigenetics.
We’re going to talk about some of her training, her postdoc work, and it’s fascinating. In her Stanford course, she looks at nutrigenomics, nutrigenetics, intermittent fasting, keto diets and the role of these interventions and personalized lifestyle and longevity medicine. She’s published research papers all over the place including in top ranked peer reviewed journals such as JAMA, Cell, Genes & Development. Lucia, it is just really great to be with you again. I am just so thrilled to be able to ping you with questions in the science of epigenetics.
Dr. Lucia Aronica: Thank you very much for having me, Kara. I hope this podcast will be as informative, as inspiring for your audience.
Dr. Kara Fitzgerald: I’m sure it will be. You and I have already dialogued about our study. Our world here has been focused, quite a bit, on epigenetics. I mean, we have a regular clinical practice in functional medicine and we do lots of other things, but we’ve put a lot of attention towards epigenetics and DNA methylation. As you know, just based on our recent study and the work that we’re going to continue to do, but you’re an epigeneticist. I mean, you’ve trained. You’ve spent your life in this field. I want you to just define epigenetics, for me. Give us like a nice few minute primer on what it is.
Dr. Lucia Aronica: Yes. Sure. Epi means on the top, so epigenetics describes a phenomenon by which molecular tags on the top of our genes can turn genes on or off. Just like a dimmer switch modulates lights up and down in a room. The magic of epigenetics can explain why cells or organisms, which have the same DNA, can actually look very different from each other and have different functions and even health states. For example, we all have in every single cell of our body the same DNA sequence and yet, our cells look different from each other. The hair cells are different from the eye cells or brain cells. This is because, although both brain cells and skin cells have the same DNA, they have different epigenetic marks that turn on different genes in our brain cells and different genes in our skin cells. The same happens for different organisms or different states of development.
Dr. Kara Fitzgerald: Yeah.
Dr. Lucia Aronica: You can think of the caterpillar and butterfly. They look very different, but they have, of course, the same DNA. During the development of the butterfly, different genes have turned on or off. So epigenetics, it can really explain how, really, genotype turns into phenotype, phenotypes that can be very different depending, also, on environmental factors.
Dr. Kara Fitzgerald: Let me ask you. That’s great. Just thinking about the butterfly and caterpillar, just a little tangentially. I was reading a paper not that long ago on royal jelly, being something that really drives epigenetic change in bees. To help to find who’s going to be a queen bee. It’s-
Dr. Lucia Aronica: Exactly. Yes. It’s another very famous example. Queen bees and worker bees in a bee hive, actually, they have the same genetics, but the queen bees are larger. They are fertile, whereas, the worker bees cannot lay eggs. Also, queen bees live 20 times longer than worker bees. Now, the only difference is an epigenetic difference. This epigenetic difference, as you mentioned, is determined during the development of a queen larva into a queen bee because only the queen larva are fed Royal Jelly, which is a protein-rich substance that turns on the genes responsible for the queen phenotype. Royal jelly is the queen maker for honeybees.
Dr. Kara Fitzgerald: I’m going to ask you later, do we want to be taking royal jelly ourselves and what’s the queen maker for us, for humans. I mean, that’s just such an extraordinary story.
Dr. Lucia Aronica: Yeah, yeah. We can discuss this later actually. Yes.
Dr. Kara Fitzgerald: We’re going to talk about. Yeah. Go ahead.
Dr. Lucia Aronica: Yeah. Yeah.
Dr. Kara Fitzgerald: You have some thoughts.
Dr. Lucia Aronica: No, I want to introduce the concept. I call these nutrients that are our royal jelly, epinutrients, because they work through an epigenetic mechanism to turn on processes that benefit our health.
Dr. Kara Fitzgerald: It’s so cool. We know DNA methylation and we’ve been bandying that about here at our platform and so forth, and you talk about it a lot as well, but how many epigenetic marks are there? A friend of mine said that epigenetics is as complex as the genome is simple. We were like, “Oh my gosh.” When the genome was finally mapped out, we’ve got less than a grape. More than a chicken but less than a grape. Our genome is really relatively simple, but epigenetics is really the exact opposite of that. Comment on that and just, really, how many epigenetic marks are in the mix helping phenotypic expression?
Dr. Lucia Aronica: Yes, there are many, several epigenetic mechanisms. The three main epigenetic mechanisms that have been best characterized so far are DNA methylation, distal modifications and small RNAs. I’ve dedicated years of my life to study each of these mechanisms. I did my PhD at the University of Vietnam, where I studied the role of small RNAs in gene expression and then I moved to the University of Oxford to where I studied histone modifications. Finally, at Stanford University where I’m looking at the link between DNA methylation and diet.
Let’s go through the function of these three modifications very briefly. Small RNAs are, I think are an exciting, one of the most exciting epigenetic regulators. Because they are, basically, mobile epigenetic modifications. They can move from the cell nucleus to the cytoplasm and actually, direct other epigenetic modifications including distal modification and DNA methylation to the right place at the right time in the cell. Then histone modifications are modifications of the histones. Histones are proteins that have the DNA coil inside the cell and get tightly packed so it can fit the cell nucleus. This is actually why genes can be turned on or off. Because when the DNA is tightly packed in the cell, the genes are turned off. The cell machineries cannot read the DNA sequence and express the gene.
In order to turn on a gene, you need to open the chromatin, which is DNA class histones, and make those genes accessible. You can do so either by using histone modifications, which are chemical modifications to the histones including methylation, acetylation, ubiquitylation and many others, or by methylating the DNA with a methyl group that is attached to cytosines. Cytosines are one of the four letters of DNA and can be methylated in the context of TG dinucleotides in our DNA, which are, yes, sites of DNA methylation. Now, when you do so, either histone modification, DNA methylation, you can create the opportunity to open certain sites of chromatin by recruiting cell machineries, proteins that open, locally, the chromatin and read the underlying DNA sequence.
Dr. Kara Fitzgerald: I just want to say, folks, that our DNA is almost six feet long, right?
Dr. Lucia Aronica: Yes.
Dr. Kara Fitzgerald: It’s really rather insane when you think about the fact that it is … When Lucia says, tightly wound, I mean, it really is packed into the nucleus of a cell. I mean, it’s just mind-blowing to think about.
Dr. Lucia Aronica: It’s incredible. It’s just like packing a 20 kilometers, like 12.6 mile long rope into a ping-pong ball.
Dr. Kara Fitzgerald: Yeah.
Dr. Lucia Aronica: It’s incredible.
Dr. Kara Fitzgerald: Right. There’s all these sophisticated activities, physiological processes happening to keep it intact and then open up a little bit of a region of it to allow that area to be expressed. It’s just mind-blowing. Let me ask you one more question on this topic since I appreciate this background. Of the three main marks, the RNA, micro RNA, the histone modifications and DNA methylation, would you say that because … The interesting thing about DNA methylation, folks, is that there are enzymes that keep the marks intact through cell division and can be heritable, can be transgenerational. I don’t know that the same is true for histone modifications or RNA. Of all of these, would you say that even though they work in concert and there’s many other chemical processes occurring, but would you nudge DNA methylation to the top of the pile or can you just not say that? Are they too interconnected?
Dr. Lucia Aronica: I would say that, for now, DNA methylation is the epigenetic modification that we have been most extensively studying in the past 10 years. The reason for that is that we have a way to measure DNA methylation very precisely at the single nucleotide resolution and to quantify changes. Also, for central lifestyle intervention. As you mentioned, we know how the mechanism of copying epigenetic information from a cell to a daughter cell works. It’s quite simple because when you have a methylation on a C on one strand, then the DNA methylases, these enzymes, the writer enzymes that write DNA methylation on our DNA, can come read that methylation and methylate the C on the corresponding, on the daughter strand of DNA or on the complementary strand. It’s a fairly simple and established mechanism. We understand that well. We have a way of measuring that very precisely.
Surprisingly, most of the studies, especially in epigenetics, especially linked to lifestyle factors such as diet, but also exposures to chemicals or tobacco. These studies have been done with DNA methylation. Now, do I believe that this is the main thing? Thus, it’s the thing that we have been studying more and we have the instrument of doing that. Being a scientist, I know that this is rarely the case. Usually, when we have a new tool and the new understanding of something, then we have a new lens through-
Dr. Kara Fitzgerald: Yes.
Dr. Lucia Aronica: I believe that there are indications that, also, the other epigenetic marks are heritable. Actually, more of these seem to play a role even in signaling, not only inside one cell, but spreading the epigenetic signals to neighbor cells. This is just something, we are just scratching the surface on that. The reason that we don’t have a precise way even of quantifying histone modifications, small RNA modifications before and after. We can measure them, but it’s much more complicated, messy-
Dr. Kara Fitzgerald: Got it.
Dr. Lucia Aronica: … from a laboratory perspective. I’ve done those tests. I must say, I love epigenetics, but I was not the best skill, the most skilled epigenetic-
Dr. Kara Fitzgerald: Chemist. Yeah.
Dr. Lucia Aronica: Chemist. It stopped. It stopped.
Dr. Kara Fitzgerald: I understand that, yeah. Just from my limited chemistry training, I wasn’t so good either. I was better at thinking through what was happening than actually doing the experiment. Yeah, it’s hard. I guess, it seems fair to assume, obviously, we’re writing and focusing on DNA methylation, but if we’re moving the epigenome, we’ve got to be influencing the other players because they’re just too intimately associated. I should say that more, I think, in our work, but I think it also goes without saying that the epigenetic mechanisms are really a symphony, they work together.
Dr. Lucia Aronica: Exactly. You just made a good point. I understand that, maybe, especially in the functional medicine world, people are more familiar with the word, “methylation.”
Dr. Kara Fitzgerald: Yes.
Dr. Lucia Aronica: To get the message across, I think it’s fair to focus on that, but as you mentioned, it’s everything interconnected and DNA methylations, very often, targeted also true, for example, small RNA and things that connect each other.
Dr. Kara Fitzgerald: Yes. I think, too, as we have more tools and then I’m going to move on from this, but it’s always great talking too as you know, because you have such a cool background. As our tools evolve and we can measure more readily, it will be finding diet and lifestyle interventions that might nuance some of these other processes and then it’ll come forward and incorporate, I think, in our language and our understanding a little bit more. Why did you decide, again, with your really interesting full background in epigenetics, why did you decide to focus on diet in epigenetics? Why did you decide to go in that direction?
Dr. Lucia Aronica: Yeah, it was a little bit of being able to marry together my passion for science and my passion for lifestyle medicine and especially food, which is, I think, the most powerful lifestyle medicine intervention that we can do every day. The field of epigenetics, really, revolutionized the way I looked at food. I realized that food is not only calories, but information is one of the most powerful signals to our genes. It’s something that we can do every day. I believe in the parietal principle. Focus on those interventions, those factors that can actually enable, allow you to reach 80% of the result. This is the case of diet. Diet is, for most people, makes 80% of the equation of a healthy lifestyle. As we discussed before, many studies point to the role of diet in epigenetics.
I also had a personal story of trying a new diet and getting my mother try the diet and experiencing profound health benefits. I really wanted to study the underlying epigenetic mechanisms of these. My story was actually, as you know, I’m an Italian, so I’ve been eating a diet of pasta or the four P’s. Pasta, pane, which is bread in English, pizza and potatoes every day until the end of my master degree and then I moved out. I moved from Italy to Vienna during my doctorate and I tried, actually, low carbohydrate diet. I increased my fat. I just had a whole food diet. No pasta, no bread. I experienced a revolution in my blood. My triglycerides went down three times. My HDL went up three times. Then I was surprised because this went against my dogma that low fat was good for your health and you just need to watch your calories and I grew up like that, I never had a weight problem, but weight is not the only measure for health.
Dr. Kara Fitzgerald: Yes. Yes.
Dr. Lucia Aronica: Anyway, I was excited by these results and then just by chance, I read that there was a Stanford study that tested high fat, low carb diet in women, in 350 women, who experienced similar changes as I did with my high fat, low carb diet. The study was by Professor Christopher Gardner and it was the pilot study for the study I am currently working on. Because then, I reached out to Christopher and I suggested I could come to Stamford and look at epigenetics for his follow up study. Now, I’m working for the diet fix clinical trial, which is the largest randomized clinical trial ever undertaken to compare low fat, low carbohydrate diet in men and women, and then looking at the DNA methylation before and after the diet. This was my idea. Just because of my passion for epigenetics and low carb and low fat nutrition.
Also, my mother tried a low carbohydrate diet. She had a brain stroke in 2014. Her doctor suggested her to go on a low fat diet to lower cholesterol and risk of another brain stroke, but I actually suggested my mother to go on a low carb diet, limit pasta, pizza and refined carbohydrates. Focus on healthy fats. She experienced the same blood lipid revolution I experienced, so that when she went back to the doctor, the doctor asked her, “What did you do?” She told him, “I did the opposite of what you told me to do. I went on a high fat diet.” Actually, she was also prescribed statin drugs and she didn’t take them. Basically, the opposite. As you can see, I’m big on lifestyle and I’m passionate about molecular biology epigenetics. That’s my story.
Dr. Kara Fitzgerald: Awesome. That’s just so great. Certainly, a lot of us have had those revelations of the power of nutrition. The fact that you did with your epigenetic training and that you’re combining forces is extraordinary, we really need you to look at that. We need epigeneticists who’ve got this nutrition training and experience, I think, to be wedding these as closely as possible. What are you seeing? Any prelim results that you can share or are you just mid-study and you’ve got their baseline and you haven’t actually run the analysis yet?
Dr. Lucia Aronica: I’ve collected the epigenetic data already two years ago. We didn’t publish the results yet. I can share with you some of the patterns that we see.
Dr. Kara Fitzgerald: Yes.
Dr. Lucia Aronica: First of all, the most exciting result, I think, is that the two diets, low fat and low carb, trigger very different epigenetic changes. The overlap is minimal. I think this is exciting because really, it tells a lot about the power of diets and nutrients, different background and pattern to turn on and off different genes. Some of the pathways that have turned on on a low carb diet include immune genes. For example, they fit to natural killer cells and some of the pathways that are turned on on a low fat diet include cancer protection genes, especially for colon cancer. Of course, we don’t know which dietary signals are responsible for these changes, whether it’s the macronutrient composition or the different nutrients from food patterns on these diets or a combination of them.
Another overall interesting result that we are now validating is that after both diets, we see a reversal of diabetes associated epigenetic DNA methylation, epigenetic changes. This is huge. In the past five years, some epigenetic biomarkers of diabetes have been identified, some candidate biomarkers, which means, basically, instead of, you may know that when people take a 23 and Me test, they receive a report saying your risk for type II diabetes is greater or lower than average. Okay. This is a genetic risk and there are a bunch of genes that you can infer a risk for developing type II diabetes, but the contribution of genetics to our risk for type II diabetes is less than 50%.
Dr. Kara Fitzgerald: Yeah.
Dr. Lucia Aronica: Lifestyle is more than 70% and some of these lifestyle, really, risk is captured, not surprisingly, in your epigenetics and DNA methylation. We identified, in the past five to 10 years, some epigenetic biomarkers of type II diabetes that change depending on our eating history. Somebody that would-
Dr. Kara Fitzgerald: Well-
Dr. Lucia Aronica: Yes.
Dr. Kara Fitzgerald: I can’t wait. I can’t wait until you publish them. Just so curious. Oh my gosh, I would love to see those biomarkers.
Dr. Lucia Aronica: Yeah. We see some changes and we are validating those data with a bigger analysis, trying to put together, also, other metabolomic markers.
Dr. Kara Fitzgerald: Interesting. Fascinating.
Dr. Lucia Aronica: Yeah, yeah. We are going to try collaboration with the group at UCL, University College London for the metabolomic analysis.
Dr. Kara Fitzgerald: That’s very exciting. Really important. I think we’ll be able … It’s not all or nothing. You definitely didn’t say, low fat is totally bad or low carb is the only diet. It sounds like we’re going to get some nuancing in our understanding.
Dr. Lucia Aronica: Yeah.
Dr. Kara Fitzgerald: I’m thrilled. Oh man, I can’t wait. I want to say, too, you’re into longevity science as well. A lot of the researchers in this arena are pretty aggressive with their interventions. There’s a little bit of a drug approach, single molecules or maybe two molecules. There’s talk of how we might use Yamanaka factors, which for folks who don’t know are transcription factors that either four of them and they can turn back a cell, a somatic cell to a pluripotent stem cell. It can basically turn back the hands of time, these Yamanaka factors and then there’s the whole CRISPR technology. The longevity scientists are really radical. Growth hormone, rapamycin, metformin, repurposing other drugs, but it’s a world that I’m very interested in and excited about and love to see what people are up to, but people can be up to some pretty intense stuff.
I think diet and lifestyle is interesting to some of these scientists, but I don’t know if they appreciate the power of it in the way that you are and the way that you’re stating it. I’m curious, your thoughts there.
Dr. Lucia Aronica: Yes. No, you touched some very important points. In the field of longevity, there are different approaches. I represent more, probably lifestyle-based nutrition longevity approach, but I’m actually excited to see some other science that is targeting single mechanisms of aging. Actually, I’m teaching a course at Stanford named, Longing for Longevity from Biology to Bio Packing. My co-teacher, she is Dr. Maddalena Adorno. She’s the CEO of a company that is developing senoblockers, so chemical agents that block the growth of so-called, senescent cells. These are zombie cells in our body that are getting old, but at the same time, they are very active in producing inflammatory molecules that trigger inflammaging in our body. Anyway, to go back to your question, so Maddalena and I represent two sides of the same coin like in longevity medicine.
I see the field of longevity medicine as a field where the different intervention have a synergistic effect and probably, incremental effect. Just like medicine and lifestyle medicine, also, longevity needs to be personalized. That’s why I think it’s important to have a more general approach that includes lifestyle in which would be probably the first horizon of longevity medicine. Focusing on what we can do now, today, and for most people, this is lifestyle, nutrition, but also, attitude to life. It’s also like meditation and stress reduction. Combining these powerful lifestyle interventions is going to make us younger, biologically. We can also discuss how your study actually demonstrated that, but I just want to add, then, probably, the second and third horizon will be then trying this more aggressive, high risk, high reward intervention that targets single mechanisms that might be relevant for a subset of people. This is where personalization is important.
Some people may have, actually, a higher burden of senescent cells and that might be the biggest trigger of aging in those people. Other people may have. Identifying what is the trigger, even aging is a complex process. Now, we know there are at least 10 different mechanisms of aging and different people may need to focus on one, two or three of them and so that’s why just to get back to your answer, I think, lifestyle, longevity medicine is now, and this is 80% of equation and then probably, the other interventions will enable to even increase our lifespan in the next years.
Dr. Kara Fitzgerald: Yeah. Yeah. That’s right. That’s great. That’s a really good synopsis. I think the flow of how we might move through these various interventions, how you’re outlining, it makes sense to me. Well, let me ask you this question. It’s just based on your last response of the 10 mechanisms of aging. I’m familiar with those, but I’m also interested in the idea that there may be some program, at least, in part driving the aging journey that were not just [sarcastic] changes, right? It’s not just oxidative stress and our toxic burden, et cetera. Yeah, of course, those are going to be driving aging, but is there an aging program? That’s something that we touched upon in our paper that, is there an actual program and could DNA methylation play a role in that program? Because we actually see, when you look at DNA methylation patterns in youth as compared to those who are older, there are almost the equal and opposite kind of patterns. It’s really rather extraordinary, right?
As we age, healthy or not, our proinflammatory genes tend to get turned on or via DNA methylation or our tumor suppressor genes. Those genes that protect us from cancer are actually inhibited and shut off. There was an interesting study looking at stem cells in healthy mice. They had the inflammaging phenotype that you’re describing, but they’re healthy. They’re not diabetic mice. You would see the same picture there in diabetic mice as well and perhaps, more so, but this idea that as we age, we may be intentionally deteriorating to clear space for younger folks is compelling that there may be a program. Even as there are also these 10 mechanisms participating. What do you think? That’s kind of a big left field question, but what are your thoughts there?
Dr. Lucia Aronica: Yeah. No, I think that there are indications that that may be the case. Even in the field of epigenetics, there are so-called epigenetic clocks that can measure the DNA methylation at different CpG sites, different genetic sites, your DNA and measure the so-called biological age, which is the epigenetic age of your cells which could be younger or older than your chronological age. Now, as you know, there are many epigenetic clocks. Some of them, actually, are better to estimate chronological age precisely, like the Horvath Clock. Some of them seem to capture better some biological age-related mechanisms, which can be senescent cells or cancer phenotypes. Now, to get back to your question, it seems that, actually, the CpGs that are more closely related to chronological age may capture that programming that you are talking about.
I think that it looks like, as we age, there is a sort of epigenetic aging, which is almost built-in. That signal is probably better captured by clocks that estimate, are more precise at estimating chronological age, but on the other side, if you think about it, the existence of clocks that are actually more closely associated to biological age is almost the biological proof, but there are other epigenetic signals that’s not necessarily programmed like so closely associated with chronological age. It can actually be affected by lifestyle.
Dr. Kara Fitzgerald: Yeah.
Dr. Lucia Aronica: I think just to get back to your question, I think there is, yes, a program, but then there are some Lego pieces on the top of the program that are very, very much influenced by lifestyle and we can control.
Dr. Kara Fitzgerald: Yes. Yes. That’s interesting. God, that’s a rabbit hole. We’ll have to dive down into, maybe, some other time. It’s pretty dense and challenging, but it speaks to potentially. I mean, our study was very, very small. We’re recruiting now for, still, a relatively small study, but hopefully, we’ll get to continue to research this for the long haul, but we were able to shift that Horvath Clock that is so closely associated with chronological age. It’s interesting, but to your point, when we do this again we’ll be looking at those second generation clocks that are more closely associated with morbidity and mortality, and actual disease state. We’re going to be looking at many more clocks, which amazingly enough, when we were designing our study back in 2017, they weren’t yet in existence. I mean, it shows how rapidly this field is just moving, just blowing up with new understandings. It’s amazing.
All right. Thank you for taking us on that really amazing tour. I want to talk to you about some of the interventions in the longevity space, the longevity/epigenetic space that you’re most excited about. I want to just, maybe any studies you’re interested in, any interventions you’re interested in and then I want to finish up our conversation today with the most important lifestyle and bio hacks that you yourself are using, that you’re recommending and just speak to, now, what we do. Tell us what we do.
Dr. Lucia Aronica: Yes, happily. Starting from that, as I mentioned, I’m a lifestyle medicine enthusiast. I apply. I practice what I preach. Every day, I actually implement lifestyle hacks in my kitchen and in my garden, when I exercise. I think, so what we can do now is really taking control of our lifestyle, first, with food and then exercise and stress control and mindfulness. There is a common language, epigenetic language that is spoken by all these intervention. This language is called, hormesis. Hormesis is a universal epigenetic language that is spoken by many organisms and plants even. Hormesis means in the Greek language, rapid motion. It describes the transition from good stress to bad stress, biologically and epigenetically.
Stress is actually one lifestyle hack that we can implement and use to improve our health. We need more good stress. This can be through food, exercise and psychological hormesis. Hormesis describes this process where low doses of stress are actually good for us. Exercise, for example, is good for us at low doses. Sunlight is good for us at low doses. Even exposure to pathogens, early life, is good for us because it can actually make us more resistant to develop allergies and other pathologies later in life. The mechanism by which these patterns is an epigenetic mechanism to which these low doses of stress actually turn on epigenetically genes that make our cells stronger and actually, younger. It’s important to use those tools, the good stress tools to trigger hormesis.
We can do that with diet, for example, the polyphenols and the epinutrients I mentioned before. Most epinutrients work through an aromatic process. They turn on the genes and make us stronger and younger. The reason for that is, as I mentioned, hormesis is a universal language, so even plants, when they are exposed to stress, they go to hormesis and they produce these phytochemicals, epinutrients in response to stress that make them more resistant to heat or cold temperature. When we eat those phytochemicals and that actually benefit from the hormesis of the plants we eat. Food is a way of incorporating hormesis in our life, exercise. I do pull ups every other day before breakfast.
In general, doing some exercise 10 minutes before a meal is a great way, actually, to boost your glucose metabolism and improve your response, glucose response to the meal. Even a little sunlight, not too much. Again, not too much sun, but exposure to sunlight can trigger hormesis in your body and psychological hormesis. Even life events that can be stressful for us like divorce or losing somebody that is important to us. This are all very sad events, but are actually from a biological standpoint, they create windows of opportunities of change. Our brain becomes more plastic, epigenetically, during those stress moments. If we manage with our attitude to life to react to those events with a positive attitude and with growth mindset, we are actually stronger afterwards. I’ve done this many times in my life. I’m a very smiling person, but I had lots of challenges. I have to thank all those adversity in life that made me what I am now, a happy and a healthy person.
Dr. Kara Fitzgerald: Yeah. That’s really beautiful. This is a great way for us to bring our podcast to a close. I love how you’ve described hormesis, but it’s such a powerful and broad understanding. I know it’s beyond just a belief that, actually, you’ve got science behind this as well. It’s just very, very cool. You’ve got this great Stanford class. You’re engaged in cool research. How can people get access to your work? How can people follow you?
Dr. Lucia Aronica: Yes. I am trying to start a YouTube channel because I posted some of my interviews or even the interviews we did on my YouTube channel. I have seen the enthusiastic feedback from both my Italian audience and the English audience. Probably, I will be uploading more videos there and I’m thinking of creating even a monthly Q&A in Italian and English with my followers, perhaps, with a patron page. You can subscribe to my YouTube channel. I’m also on Instagram with the name Epi Wellness or Dr. Aronica. I have a website, Dr. Aronica, where you can find links to enroll in my Stanford courses.
Dr. Kara Fitzgerald: Yay. I would get to it. I listened in. I was a fly on the wall for a portion of your course before we talked about our study and it was bad ass. It was a great course. I’ll take it. I’ll absolutely take it when I can.
Dr. Lucia Aronica: Right. Thank you. Thank you. You’ll be the best student.
Dr. Kara Fitzgerald: To be continued. All right, Dr. Aronica, thank you so much for joining me at New Frontiers.
Dr. Lucia Aronica: Thank you very much for having me, Kara.
Dr. Kara Fitzgerald: And that wraps up another amazing conversation with a great mind in functional medicine. I am so glad that you could join me. None of this would be possible, through the years, without our generous, wonderful sponsors, including Integrative Therapeutics, Metagenics, and Biotics. These are companies that I trust, and I use with my patients, every single day. Visit them at IntegativePro.com, BioticsResearch.com, and Metagenics.com. Please tell them that I sent you and thank them for making New Frontiers in Functional Medicine possible.
And one more thing? Leave a review and a thumbs-up on iTunes or Soundcloud or wherever you’re hearing my voice. These kinds of comments will promote New Frontiers in Functional Medicine getting the word on functional medicine out there to greater community. And for that, I thank you.
Dr. Lucia Aronica, Ph.D., is Lecturer at the Stanford Prevention and Research Center, and R&D Lead, Genomics, at Metagenics Inc. Her research and teaching focus on how lifestyle can change gene expression thorough a process called epigenetics, and how we can use this information to design personalized lifestyle interventions for optimal health and longevity. Some topics of her courses include nutrigenomics and nutrigenetics, intermittent fasting and ketogenic diets, and the role of these interventions in personalized lifestyle medicine and longevity medicine. She has published research papers in top-ranked peer-reviewed journals such as JAMA, Cell, and Genes and Development.
Dr. Fitzgerald Study on Reversing Epigenetic Age
Dr. Kara Fitzgerald FxMed Resources
Clinic: Patient consults with DrKF physicians
Clinician Professional Development: DrKF FxMed Clinic Immersion
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