Podcasts about Epigenome

In this episode of the Epigenetics Podcast, we talked with Ferdinand von Meyenn from ETH Zürich about his work on the interplay of nutrition, metabolic pathways, and epigenetic regulation. To start Dr. Meyenn recounts his pivotal research on DNA methylation in naive embryonic stem cells during his time with Wolf Reick. He explains the dynamics of global demethylation in naive stem cells, revealing the key enzymes involved and the unexpected findings surrounding UHF1—its role in maintaining DNA methylation levels and influencing the methylation landscape during early embryonic development. Dr. Meyenn then shares his perspective on the scientific transition to establishing his own lab at ETH. He reflects on his ambitions to merge the fields of metabolism and epigenetics, which is a recurring theme throughout his research. By investigating the interplay between metabolic changes and epigenetic regulation, he aims to uncover how environmental factors affect cellular dynamics across various tissues. This leads to a discussion of his recent findings on histone lactylation and its implications in cellular metabolism, as well as the intricacies of epigenetic imprinting in stem cell biology. Last but not least we touch upon Dr. Meyenn's most recent study, published in Nature, investigating the epigenetic effects of obesity. He provides a detailed overview of how adipose tissue undergoes transcriptional and epigenetic rearrangements during weight fluctuations. The conversation highlights the notion of epigenetic memory in adipocytes, showing how obesity is not just a temporary state but leaves lasting cellular changes that can predispose individuals to future weight regain after dieting. This exploration opens avenues for potential therapeutic interventions aimed at reversing adverse epigenetic modifications.   References von Meyenn, F., Iurlaro, M., Habibi, E., Liu, N. Q., Salehzadeh-Yazdi, A., Santos, F., Petrini, E., Milagre, I., Yu, M., Xie, Z., Kroeze, L. I., Nesterova, T. B., Jansen, J. H., Xie, H., He, C., Reik, W., & Stunnenberg, H. G. (2016). Impairment of DNA Methylation Maintenance Is the Main Cause of Global Demethylation in Naive Embryonic Stem Cells. Molecular cell, 62(6), 848–861. https://doi.org/10.1016/j.molcel.2016.04.025 Galle, E., Wong, C. W., Ghosh, A., Desgeorges, T., Melrose, K., Hinte, L. C., Castellano-Castillo, D., Engl, M., de Sousa, J. A., Ruiz-Ojeda, F. J., De Bock, K., Ruiz, J. R., & von Meyenn, F. (2022). H3K18 lactylation marks tissue-specific active enhancers. Genome biology, 23(1), 207. https://doi.org/10.1186/s13059-022-02775-y Agostinho de Sousa, J., Wong, C. W., Dunkel, I., Owens, T., Voigt, P., Hodgson, A., Baker, D., Schulz, E. G., Reik, W., Smith, A., Rostovskaya, M., & von Meyenn, F. (2023). Epigenetic dynamics during capacitation of naïve human pluripotent stem cells. Science advances, 9(39), eadg1936. https://doi.org/10.1126/sciadv.adg1936 Bonder, M. J., Clark, S. J., Krueger, F., Luo, S., Agostinho de Sousa, J., Hashtroud, A. M., Stubbs, T. M., Stark, A. K., Rulands, S., Stegle, O., Reik, W., & von Meyenn, F. (2024). scEpiAge: an age predictor highlighting single-cell ageing heterogeneity in mouse blood. Nature communications, 15(1), 7567. https://doi.org/10.1038/s41467-024-51833-5 Hinte, L. C., Castellano-Castillo, D., Ghosh, A., Melrose, K., Gasser, E., Noé, F., Massier, L., Dong, H., Sun, W., Hoffmann, A., Wolfrum, C., Rydén, M., Mejhert, N., Blüher, M., & von Meyenn, F. (2024). Adipose tissue retains an epigenetic memory of obesity after weight loss. Nature, 636(8042), 457–465. https://doi.org/10.1038/s41586-024-08165-7   Related Episodes Nutriepigenetics: The Effects of Diet on Behavior (Monica Dus) Epigenetic and Metabolic Regulation of Early Development (Jan Żylicz) Effects of Environmental Cues on the Epigenome and Longevity (Paul Shiels)   Contact Epigenetics Podcast on Mastodon Epigenetics Podcast on Bluesky Dr. Stefan Dillinger on LinkedIn Active Motif on LinkedIn Active Motif on Bluesky Email: podcast@activemotif.com

In this episode, Brian Joyce discusses a groundbreaking study that examines the link between DNA methylation and the incidence of cardiovascular disease and cancer across three major cohorts. The research identifies shared epigenetic signatures associated with both diseases, highlighting the need for further investigation into their functional implications and potential clinical applications in diverse populations.

In this week's episode of the Everything Epigenetics podcast, I'm joined by Dr. Charles Breeze, an expert in computational epigenetics. We talk about his inspiring journey into the field of epigenetics, his trailblazing research on kidney function across diverse ethnic groups, and the innovative tools he's developed to push the boundaries of epigenetic research.Dr. Breeze shares how his fascination with the complex interaction between environmental and genetic factors shaped his path into epigenetics. This passion led him to focus on understanding why certain populations are at higher risk for diseases like chronic kidney disease. His work has uncovered insights into the disparities in kidney disease risk among different ethnic groups, shedding light on genetic and environmental factors that had previously been overlooked.To address the challenges of inclusivity and precision in epigenetic studies, Dr. Breeze developed specialized tools that enhance the accuracy of Epigenome-Wide Association Studies (EWAS). These tools aim to improve how we analyze the impact of genetics and environment on health, helping researchers study epigenetic patterns across populations more effectively. His contributions are making it easier to identify how factors like diet, stress, and pollution affect gene expression, paving the way for more inclusive and equitable health research.Dr. Breeze earned his Ph.D. in computational epigenetics and genomics from University College London, where he was a Marie Curie fellow. He has also worked at top institutions like the University of Oxford, the European Bioinformatics Institute, and the Altius Institute for Biomedical Sciences in Seattle. There, he led the analysis and creation of important mouse genome data. Dr. Breeze has developed bioinformatics tools like eFORGE and FORGE2, which help analyze data from studies on how genes and the environment affect health (EWAS and GWAS). Dr. Breeze is a member of the Encyclopedia of DNA Elements (ENCODE) and the International Human Epigenome Consortium (IHEC).You'll learn about:  - Dr. Breeze's early interest in genomics, sparked by reading "Genome" by Matthew Ridley  - His significant findings from the 2021 study titled “Epigenome-wide association study of kidney function identifies trans-ethnic and ethnic-specific loci,” which revealed ethnic disparities in kidney function  - The challenges faced in epigenetic research due to the lack of diversity in reference data and how this impacts research outcomes  - Proposed solutions to increase diversity in epigenomic data, including community involvement and targeted data generation  - How his bioinformatics tools, eFORGE and FORGE2, assist researchers in understanding the complex data from EWAS and GWAS studies  - His future research directions, including studies on kidney cancer and the expansion of pathway analysis toolsSupport the showWhere to Find Us:Instagram Twitter Facebook Follow us on:Apple Podcast Spotify YouTube Visit our website for more information and resources: everythingepigenetics.com Thank you for joining us at the Everything Epigenetics Podcast and remember you have control over your Epigenetics, so tune in next time to learn more about how to harness this knowledge for your benefit.

Welcome to episode 053 of Life Sciences 360.In this episode of Life Science 360, our host Harsh Thakkar sits down with Brian Cosgrove, Principal Scientist at Tune Therapeutics. Brian dives deep into the fascinating world of epigenetics and its role in developing therapies for complex diseases. He shares insights on how Tune Therapeutics is leveraging the power of the epigenome to create innovative treatments, particularly focusing on their work with hepatitis B and the promising potential of their tempo platform.Chapters:00:00 - Introduction00:02 - Understanding Cell Differentiation and Gene Regulation00:37 - Welcome Brian Cosgrove from Tune Therapeutics01:15 - Brian's Transition from Duke University to Tune Therapeutics02:03 - The Basics of Epigenetic Tuning02:38 - How Epigenetics Determines Cell Function03:55 - The Role of the Epigenome in Gene Expression05:06 - The Complexity of the Human Body and Scientific Research06:12 - Deep Dive into Hepatitis B (HBV)06:57 - Current Treatments for Chronic Hepatitis B08:32 - The Unmet Need in Hepatitis B Treatment09:09 - Brian's Career Path and Decision to Join Tune Therapeutics12:03 - Growth and Evolution of Tune Therapeutics15:25 - Challenges and Rewards of Joining an Early-Stage Company17:49 - Introduction to the Tempo Platform19:04 - How Tempo Platform Works with HBV20:32 - Epigenetic Regulation of HBV23:20 - Future Applications of Epigenetic Tuning24:38 - Timeline for Tune 401 Clinical Trials26:08 - Anticipated Challenges and Solutions27:20 - Partnering for Manufacturing and Delivery28:32 - The Broader Field of Epigenetic Therapies30:21 - Potential Global Impact of Epigenetic Therapies32:12 - The Most Rewarding Part of Brian's Work33:01 - The Personal Side of Working in Life Sciences35:10 - Final Thoughts and Future Outlook for Tune Therapeutics36:09 - Closing Remarks and How to Connect with BrianStay tuned and don't forget to subscribe for more in-depth conversations with leading scientists and innovators in the life sciences field!----- Links:*Brian Cosgrove LinkedIn (https://www.linkedin.com/in/brian-cosgrove-171b926/)*Tune Therapeutics LinkedIn (https://www.linkedin.com/company/tunetx/ )*Tune Therapeutics website (https://tunetx.com/)*Harsh Thakkar LinkedIn ( https://www.linkedin.com/in/harshvthakkar/ )*Listen to this episode on the go! 

We are entering a new phase of understanding how our social environments affect our biology, particularly how they influence the genes involved in brain development and function. This knowledge helps us see how experiences like stress, trauma, and isolation can cause changes at the molecular level that may increase the risk of mental disorders. On the other hand, we're also exploring how positive experiences induced by psychedelics, which create feelings of unity and insight, might lead to beneficial molecular changes.Most mental health disorders, whether psychiatric, neurodevelopmental, or neurodegenerative, arise from both genetic and environmental factors. Recognizing this, research now combines studies of these exposures with molecular biology to better understand how our behaviors and environments can directly impact our genetic expression, shedding light on why some people are more vulnerable to mental health issues. This field, known as behavioral epigenetics, explores how our experiences can shape our genetic makeup and influence our brain health.In this week's episode of the Everything Epigenetics podcast, Dr. Candace Lewis shares her insights into epigenetics, discussing how early life stress can affect gene regulation and how attachment and societal influences shape our biology. The conversation then turns to psychedelics, with Candace outlining the history and ongoing research into their potential as a therapeutic tool for mental health disorders. She explains the mechanics of psychedelic-assisted therapy and the importance of understanding its broader context.We then chat about the therapeutic possibilities of psychedelics and their role in epigenetics, and the importance of creating a safe environment for individuals to explore their emotions and experiences with psychedelics. Candace draws parallels between acute stress and the psychedelic state, suggesting that research into psychedelics could reveal important information about the epigenetic changes they induce. Lastly, Candace also mentions the Psychedelic Genome Project and the significance of collecting data to advance the field.Candace is currently the director of the BEAR Lab at Arizona State University aiming to acknowledge the harm caused by psychology and genetic sciences on minorly groups, increase diversity in training and study cohorts, and change policy to improve mental health for all.In this episode of Everything Epigenetics, you'll learn about: The Brain, Epigenetics, & Altered states Research (BEAR) labComplex relationships between experiences that shape cognition, mood, and behaviorHow stress, trauma, and lack of connection may lead to molecular changes that increase risk for mental disorders.Candace's editorial: What is up with psychedelics anyway?How epigenetics shed light on psychedelic therapyMDMA-assisted therapy DNA methylation of gene systems involved in addiction, cognition, stress, and immune functionHow DNA methylation is associated with MDMA-assisted therapy treatment response for severe PTSDThe hypothalamic-Pituitary-Adrenal (HPA) AxisSimilarities between the acute stress response and the psychedelic stateThe psychedelic Genome Project (PGP)Where to find Candace:- ASU profile- LinkedIn Support the Show.Thank you for joining us at the Everything Epigenetics Podcast and remember you have control over your Epigenetics, so tune in next time to learn more about how.

Professor Doudna was awarded the 2020 Nobel Prize in Chemistry with Professor Emmanuelle Charpentier for their pioneering work in CRISPR genome editing. The first genome editing therapy (Casgevy) was just FDA approved, only a decade after the CRISPR-Cas9 editing system discovery. But It's just the beginning of a much bigger impact story for medicine and life science.Ground Truths podcasts are now on Apple and Spotify. And if you prefer videos, they are posted on YouTubeTranscript with links to audio and relevant external linksEric Topol (00:06):This is Eric Topol with Ground Truths, and I'm really excited today to have with me Professor Jennifer Doudna, who heads up the Innovative Genomics Institute (IGI) at UC Berkeley, along with other academic appointments, and as everybody knows, was the Nobel laureate for her extraordinary discovery efforts with CRISPR genome editing. So welcome, Jennifer.Jennifer Doudna (00:31):Hello, Eric. Great to be here.Eric Topol (00:34):Well, you know we hadn't met before, but I felt like I know you so well because this is one of my favorite books, The Code Breaker. And Walter Isaacson did such a wonderful job to tell your story. What did you think of the book?My interview with Walter Isaacson on The Code Breaker, a book I highly recommendJennifer Doudna (00:48):I thought Walter did a great job. He's a good storyteller, and as you know from probably from reading it or maybe talking to others about it, he wrote a page turner. He actually really dug into the science and all the different aspects of it that I think created a great tale.Eric Topol (01:07):Yeah, I recommended highly. It was my favorite book when it came out a couple years ago, and it is a page turner. In fact, I just want to read one, there's so many quotes out of it, but in the early part of the book, he says, “the invention of CRISPR and the plague of Covid will hasten our transition to the third great revolution of modern times. These revolutions arose from the discovery beginning just over a century ago, of the three fundamental kernels of our existence, the atom, the bit, and the gene.” That kind of tells a big story just in one sentence, but I thought I'd start with the IGI, the institute that you have set up at Berkeley and what its overall goals are.Jennifer Doudna (01:58):Right. Well, let's just go back a few years maybe to the origins of this institute and my thinking around it, because in the early days of CRISPR, it was clear that we were really at a moment that was quite unique in the sense that there was a transformative technology. It was going to intersect with lots of other discoveries and technologies. And I work at a public institution and my question to myself was, how can I make sure that this powerful tool is first of all used responsibly and secondly, that it's used in a way that benefits as many people as possible, and it's a tall order, but clearly we needed to have some kind of a structure that would allow people to work together towards those goals. And that was really the mission behind the IGI, which was started as a partnership between UC Berkeley and UCSF and now actually includes UC Davis as well.The First FDA Approved Genome EditingEric Topol (02:57):I didn't realize that. That's terrific. Well, this is a pretty big time because 10 years or so, I guess starting to be 11 when you got this thing going, now we're starting to see, well, hundreds of patients have been treated and in December the FDA approved the first CRISPR therapy for sickle cell disease, Casgevy. Is that the way you say it?Jennifer Doudna (03:23):Casgevy, yeah.Eric Topol (03:24):That must have felt pretty good to see if you go from the molecules to the bench all the way now to actually treating diseases and getting approval, which is no easy task.Jennifer Doudna (03:39):Well, Eric, for me, I'm a biochemist and somebody who has always worked on the fundamentals of biology, and so it's really been extraordinary to see the pace at which the CRISPR technology has been adopted, and not just for fundamental research, but also for real applications. And Casgevy is sort of the crowning example of that so far, is that it's really a technology that we can already see how it's being used to, I think it's fair to say, effectively cure a genetic disease for the first time. Really amazing.Genome Editing is Not the Same as Gene TherapyEric Topol (04:17):Yeah. Now I want to get back to that. I know there's going to be refinements about that. And of course, there's beta thalassemia, so we've got two already, and our mutual friend Fyodor Urnov would say two down 5,000 to go. But I think before I get to the actual repair of the sickle cell defect molecular defect, I think one of the questions I think that people listeners may not know is the differentiation of genome editing with gene therapy. I mean, as you know, there was recently a gene therapy approval for something like $4.25 million for metachromatic leukodystrophy. So maybe you could give us kind of skinny on how these two fundamental therapies are different.Jennifer Doudna (05:07):Right. Well, it's a great question because the terminology sounds kind of the same, and so it could be confusing. Gene therapy goes back decades, I can remember gene therapy being discussed as an exciting new at the time, direction back when I was a graduate student. That was little while ago. And it refers to the idea that we can use a genetic approach for disease treatment or even for a cure. However, it fundamentally requires some mechanism of integrating new information into a genome. And traditionally that's been done using viruses, which are great at doing that. It's just that they do it wherever they want to do it, not necessarily where we want that information to go. And this is where CRISPR comes in. It's a technology allows precision in that kind of genetic manipulation. So it allows the scientist or the clinician to decide where to make a genetic change. And that gives us tremendous opportunity to do things with a kind of accuracy that hasn't been possible before.Eric Topol (06:12):Yeah, no question. That's just a footnote. My thesis in college at University of Virginia, 1975, I'm an old dog, was prospects for gene therapy in man. So it took a while, didn't it? But it's a lot better now with what you've been working on, you and your colleagues now and for the last decade for sure. Now, what I was really surprised about is it's not just of course, these hemoglobin disorders, but now already in phase two trials, you've got hereditary angioedema, which is a life-threatening condition, amyloidosis, cancer ex vivo, and also chronic urinary tract infections. And of course, there's six more others like autoimmune diseases like lupus and type 1 diabetes. So this is really blossoming. It's really extraordinary.Eric Topol (07:11):I mean, wow. So one of the questions I had about phages, because this is kind of going back to this original work and discovery, antimicrobial resistance is really a big problem and it's a global health crisis, and there's only two routes there coming up with new drugs, which has been slow and not really supported by the life science industry. And the other promising area is with phages. And I wonder, since this is an area you know so well, why haven't we put more, we're starting to see more trials in phages. Why haven't we doubled down or tripled down on this to help the antimicrobial resistance problem?Jennifer Doudna (08:00):Well, it's a really interesting area, and as you said, it's kind of one of those areas of science where I think there was interest a while ago and some effort was made for reasons that are not entirely clear to me, at least it fizzled out as a real focused field for a long time. But then more recently, people have realized that there's an opportunity here to take advantage of some natural biology in which viruses can infect and destroy microbes. Why aren't we taking better advantage of that for our own health purposes? So I personally am very excited about this area. I think there's a lot of fundamental work still to be done, but I think there's a tremendous opportunity there as well.CRISPR 2.0Eric Topol (08:48):Yeah, I sure think we need to invest in that. Now, getting back to this sickle cell story, which is so extraordinary. This is kind of a workaround plan of getting fetal hemoglobin built up, but what about actually repairing, getting to fixing the lesion, if you will?Eric Topol (09:11):Yeah. Is that needed?Jennifer Doudna (09:13):Well, maybe it's worth saying a little bit about how Casgevy works, and you alluded to this. It's not a direct cure. It's a mechanism that allows activation of a second protein called fetal hemoglobin that can suppress the effect of the sickle cell mutation. And it's great, and I think for patients, it offers a really interesting opportunity with their disease that hasn't been available in the past, but at the same time, it's not a true cure. And so the question is could we use a CRISPR type technology to actually make a correction to the genetic defect that directly causes the disease? And I think the answer is yes. The field isn't there quite yet. It's still relatively difficult to control the exact way that DNA editing is occurring, especially if we're doing it in vivo in the body. But boy, many people are working on this, as you probably know. And I really think that's on the horizon.Eric Topol (10:19):Yeah. Well, I think we want to get into the in vivo story as well because that, I think right now it's so complicated for a person to have to go through the procedure to get ultimately this treatment currently for sickle cell, whereas if you could do this in vivo and you could actually get the cure, that would be of the objective. Now, you published just earlier this month in PNAS a wonderful paper about the EDVs and the lipid nanoparticles that are ways that we could get to a better precision editing. These EDVs I guess if I have it right, enveloped virus-like particles. It could be different types, it could be extracellular vesicles or whatnot. But do you think that's going to be important? Because right now we're limited for delivery, we're limited to achieve the right kind of editing to do this highly precise. Is that a big step for the future?Jennifer Doudna (11:27):Really big. I think that's gating at the moment. Right now, as you mentioned, somebody that might want to get the drug Casgevy for sickle cell disease or thalassemia, they have to go through a bone marrow transplant to get it. And that means that it's very expensive. It's time consuming. It's obviously not pleasant to have to go through that. And so that automatically means that right now that therapy is quite restricted in the patients that it can benefit. But we imagine a day when you could get this type of therapy into the body with a one-time injection. Maybe someday it's a pill that could be taken where the gene editors target the right cells in the body. In diseases like that, it would be the stem cells in the bone marrow and carry out gene editing that can have a therapeutic benefit. And again, it's one of those ideas that sounds like science fiction, and yet already there's tremendous advance in that direction. And I think over the next, I don't know, I'm guessing 5 to 10 years we're going to see that coming online.Editing RNA, the Epigenome, and the MicrobiomeEric Topol (12:35):Yeah, I'm guessing just because there's so much work on the lipid nanoparticles to tweak them. And there's four different components that could easily be made so much better. And then all these virus-like proteins, I mean, it may happen even sooner. And it's really exciting. And I love that diagram in that paper. You have basically every organ of the body that isn't accessible now, potentially that would become accessible. And that's exciting because whatever blossoming we're seeing right now with these phase two trials ongoing, then you basically have no limits. And that I think is really important. So in vivo editing big. Now, the other thing that's cropped up in recent times is we've just been focused on DNA, but now there's RNA editing, there's epigenetic or epigenomic editing. What are your thoughts about that?Jennifer Doudna (13:26):Very exciting as well. It's kind of a parallel strategy. The idea there would be to, rather than making a permanent change in the DNA of a cell, you could change just the genetic output of the cell and or even make a change to DNA that would alter its ability to be expressed and to produce proteins in the cell. So these are strategies that are accessible, again, using CRISPR tools. And the question is now how to use them in ways that will be therapeutically beneficial. Again, topics that are under very active investigation in both academic labs and at companies.Eric Topol (14:13):Yeah. Now speaking of that, this whole idea of rejuvenation, this is Altos. You may I'm sure know my friend here, Juan Carlos Belmonte, who's been pushing on this for some time at Altos now formerly at Salk. And I know you helped advise Altos, but this idea of basically epigenetic, well using the four Yamanaka factors and basically getting cells that go to a state that are rejuvenated and all these animal models that show that it really happens, are you thinking that really could become a therapy in the times ahead in patients for aging or particular ideas that you have of how to use that?Jennifer Doudna (15:02):Well, you mentioned the company Altos. I mean, Altos and a number of other groups are actively investigating this. Not I would say specifically regarding genome editing, although being able to monitor and probably change gene functions that might affect the aging process could be attractive in the future. I think the hard question there is which genes do we tweak and how do we make sure that it's safe? And better than me I mean, that's a very difficult thing to study clinically because it takes time for one thing, and we probably don't have the best models either. So I think there are challenges there for sure. But along the way, I feel very excited about the kind of fundamental knowledge that will come from those studies. And in particular, this question of how tissues rejuvenate I think is absolutely fascinating. And some organisms do this better than others. And so, understanding how that works in organisms that are able to say regrow a limb, I think can be very interesting.Eric Topol (16:10):And that gets me to that recent study. Well, as you well know, there's a company Verve that's working on the familial hypercholesterolemia and using editing with the PCSK9 through the liver and having some initial, at least a dozen patients have been treated. But then this epigenetic study of editing in mice for PCSK9 also showed results. Of course, that's much further behind actually treating patients with base editing. But it's really intriguing that you can do some of these things without having to go through DNA isn't it?Jennifer Doudna (16:51):Amazing, right? Yeah, it's very interesting.Reducing the Cost of Genome EditingEric Topol (16:54):Wild. Now, one of the things of course that people bring up is, well, this is so darn expensive and it's great. It's a science triumph, but then who can get these treatments? And recently in January, you announced a Danaher-IGI Beacon, and maybe you can tell us a bit about that, because again, here's a chance to really markedly reduce the cost, right?Jennifer Doudna (17:25):That's right. That's the vision there. And huge kudos to my colleague Fyodor Urnov, who really spearheaded that effort and leads the team on the IGI side. But the vision there was to partner with a company that has the ability to manufacture molecules in ways that are very, very hard, of course, for academic labs and even for most companies to do. And so the idea was to bring together the best of genome editing technology, the best of clinical medicine, especially focused on rare human diseases. And this is with our partners at UCSF and with the folks in the Danaher team who are experts at downstream issues of manufacturing. And so the hope there is that we can bring those pieces together to create ways of using CRISPR that will be cost effective for patients. And frankly, we'll also create a kind of roadmap for how to do this, how to do this more efficiently. And we're kind of building the plane while we're flying it, if you know what I mean. But we're trying to really work creatively with organizations like the FDA to come up with strategies for clinical trials that will maintain safety, but also speed up the timeline.Eric Topol (18:44):And I think it's really exciting. We need that and I'm on the scientific advisory board of Danaher, a new commitment for me. And when Fyodor presented that recently, I said, wow, this is exciting. We haven't really had a path to how to get these therapies down to a much lower cost. Now, another thing that's exciting that you're involved in, which I think crosses the whole genome editing, the two most important things that I've seen in my lifetime are genome editing and AI, and they also work together. So maybe before we get into AI for drug discovery, how does AI come into play when you're thinking about doing genome editing?Jennifer Doudna (19:34):Well, the thing about CRISPR is that as a tool, it's powerful not only as a one and done kind of an approach, but it's also very powerful genomically, meaning that you can make large libraries of these guide RNAs that allow interrogation of many genes at once. And so that's great on the one hand, but it's also daunting because it generates large collections of data that are difficult to manually inspect. And in some cases, I believe really very, very difficult to analyze in traditional ways. But imagine that we have ways of training models that can look at genetic intersections, ways that genes might be affecting the behavior of not only other genes, but also how a person responds to drugs, how a person responds to their environment and allows us to make predictions about genetic outcomes based on that information. I think that's extremely exciting, and I definitely think that over the next few years we'll see that kind of analysis coming online more and more.Eric Topol (20:45):Yeah, the convergence, I think is going to be, it's already being done now, but it's just going to keep building. Now, Demis Hassabis, who one of the brilliant people in the field of AI leads the whole Google Deep Mind AI efforts now, but he formed after AlphaFold2 behaving to predict proteins, 200 million proteins of the universe. He started a company Isomorphic Labs as a way to accelerate using AI drug discovery. What can you tell us about that?Jennifer Doudna (21:23):It's exciting, isn't it? I'm on the SAB for that company, and I think it's very interesting to see their approach to drug discovery. It's different from what I've been familiar with at other companies because they're really taking a computational lens to this challenge. The idea there is can we actually predict things like the way a small molecule might interact with a particular protein or even how it might interact with a large protein complex. And increasingly because of AlphaFold and programs like that, that allow accurate prediction of structures, it's possible to do that kind of work extremely quickly. A lot of it can be done in silico rather than in the laboratory. And when you do get around to doing experiments in the lab, you can get away with many fewer experiments because you know the right ones to do. Now, will this actually accelerate the rate at which we get to approved therapeutics? I wonder about your opinion about that. I remain unsure.Editing Out Alzheimer's Risk AllelesEric Topol (22:32):Yeah. I mean, we have one great success story so far during the pandemic Baricitinib, a drug that repurposed here, a drug that was for rheumatoid arthritis, found by data mining that have a high prospects for Covid and now saves lives in Covid. So at least that's one down, but we got a lot more here too. But it, it's great that Demis recruited you on the SAB for Isomorphic because it brings in a great mind in a different field. And it goes back to one of the things you mentioned earlier is how can we get some of this genome editing into a pill someday? Wow. Now, one of the things that for personal interest, as an APOE4 carrier, I'm looking to you to fix my APOE4 and give me APOE2. How can I expect to get that done in the near future?Jennifer Doudna (23:30):Oh boy. Okay, we'll have to roll up our sleeves on that one. But it is appealing, isn't it? I think about it too. It's a fascinating idea. Could we get to a point someday where we can use genome editing as a prophylactic, not as a treatment after the fact, but as a way to actually protect ourselves from disease? And the APOE4 example is a really interesting one because there's really good evidence that by changing the type of allele that one has for the APOE gene, you can actually affect a person's likelihood of developing Alzheimer's in later life. But how do we get there? I think one thing to point out is that right now doing genome editing in the brain is, well, it's hard. I mean, it's very hard.Eric Topol (24:18):It a little bit's been done in cerebral spinal fluid to show that you can get the APOE2 switch. But I don't know that I want to sign up for an LP to have that done.Jennifer Doudna (24:30):Not quite yet.Eric Topol (24:31):But someday it's wild. It's totally wild. And that actually gets me back to that program for coronary heart disease and heart attacks, because when you're treating people with familial hypercholesterolemia, this extreme phenotype. Someday and this goes for many of these rare diseases that you and others are working on, it can have much broader applicability if you have a one-off treatment to prevent coronary disease and heart attacks and you might use that for people well beyond those who have an LDL cholesterol that are in the thousands. So that's what I think a lot of people don't realize that this editing potential isn't just for these monogenic and rare diseases. So we just wanted to emphasize that. Well, this has been a kind of wild ride through so much going on in this field. I mean, it is extraordinary. What am I missing that you're excited about?Jennifer Doudna (25:32):Well, we didn't talk about the microbiome. I'll just very briefly mention that one of our latest initiatives at the IGI is editing the microbiome. And you probably know there are more and more connections that are being made between our microbiome and all kinds of health and disease states. So we think that being able to manipulate the microbiome precisely is going to open up another whole opportunity to impact our health.Can Editing Slow the Aging Process?Eric Topol (26:03):Yeah, I should have realized that when I only mentioned two layers of biology, there's another one that's active. Extraordinary, just going back to aging for a second today, there was a really interesting paper from Irv Weissman Stanford, who I'm sure you know and colleagues, where they basically depleted the myeloid stem cells in aged mice. And they rejuvenated the immune system. I mean, it really brought it back to life as a young malice. Now, there probably are ways to do that with editing without having to deplete stem cells. And the thought about other ways to approach the aging process now that we're learning so much about science and about the immune system, which is one of the most complex ones to work in. Do you have ideas about that are already out there that we could influence the aging process, especially for those of us who are getting old?Jennifer Doudna (27:07):We're all on that path, Eric. Well, I guess the way that I think about it is I like to think that genome editing is going to pave the way to make those kinds of fundamental discoveries. I still feel that there's a lot of our genetics that we don't understand. And so, by being able to manipulate genes precisely and increasingly to look at how genes interact with each other, I think one fundamental question it relates to aging actually is why do some of us age at a seemingly faster pace than others? And it must have to do at least in part with our genetic makeup and how we respond to our environment. So I definitely think there are big opportunities there, really in fundamental research initially, but maybe later to actually change those kinds of things.Eric Topol (28:03):Yeah, I'm very impressed in recent times how much the advances are being made at basic science level and experimental models. A lot of promise there. Now, is there anything about this field that you worry about that keeps you up at night that you think, besides, we talked about that we got to get the cost down, we have to bridge health inequities for sure, but is there anything else that you're concerned about right now?Jennifer Doudna (28:33):Well, I think anytime a new technology goes into clinical trials, you worry that things may get out ahead of their skis, and there may be some overreach that happens. I think we haven't really seen that so far in the CRISPR field, which is great. But I guess I remain cautious. I think that we all saw what happened in the field of gene therapy now decades ago, but that really put a poll on that field for a long time. And so, I definitely think that we need to continue to be very cautious as gene editing continues to advance.Eric Topol (29:10):Yeah, no question. I think the momentum now is getting past that point where you would be concerned about known unknowns, if you will, things that going back to the days of the Gelsinger crisis. But it's really extraordinary. I am so thrilled to have this conversation with you and to get a chance to review where the field is and where it's going. I mean, it's exploding with promise and potential well beyond and faster. I mean, it takes a drug 17 years, and you've already gotten this into two treatments. I mean, I'm struck when you were working on this, how you could have thought that within a 10-year time span you'd already have FDA approvals. It's extraordinary.Jennifer Doudna (30:09):Yeah, we hardly dared hope. Of course, we're all thrilled that it went that fast, but I think it would've been hard to imagine it at the time.Eric Topol (30:17):Yeah. Well, when that gets simplified and doesn't require hospitalizations and bone marrow, and then you'll know you're off to the races. But look, what a great start. Phenomenal. So congratulations. I'm so thrilled to have the chance to have this conversation. And obviously we're all going to be following your work because what a beacon of science and progress and changing medicine. So thanks and give my best to my friend there at IGI, Fyodor, who's a character. He's a real character. I love the guy, and he's a good friend.Jennifer Doudna (30:55):I certainly will Eric, and thank you so much. It's been great talking with you.*******************************************************Thanks for listening and/or reading this edition of Ground Truths.I hope you found it as stimulating as I did. Please share if you did!A reminder that all Ground Truths posts (newsletter and podcast( are free without ads. Soon we'll set it up so you can select what type of posts you want to be notified about.If you wish to be a paid subscriber, know that all proceeds are donated to Scripps Research, and thanks for that—it greatly helped fund our summer internship program for 2023 and 2024.Thanks to my producer Jessica Nguyen and to Sinjun Balabanoff for audio/video support. Get full access to Ground Truths at erictopol.substack.com/subscribe

Lead Story: Epigenome-wide association study on methamphetamine dependence Addiction Biology The authors of this study postulate that some of the biologic changes resulting from methamphetamine use may be associated with epigenetic changes from DNA methylation. Such associations have been seen in schizophrenia, mood disorder, obsessive-compulsive disorder, and Parkinson's disease. Subjects with methamphetamine dependence (n=24) as well as age and sex matched controls had an epigenome-wide analysis of DNA methylation and identification of sites where methylation differed between subjects with methamphetamine dependence and controls. Thirteen regions with differential methylation were found. Of particular interest was hypomethylation of the CNOT1 and PUM1 genes leading to alterations in mRNA metabolism similar to those seen in bipolar disorder and schizophrenia. These changes relate to symptoms in common such as psychosis. The authors conclude that symptoms seen in methamphetamine dependency may result from genetic changes similar to those in other psychiatric disorders.   Read this issue of the ASAM Weekly Subscribe to the ASAM Weekly Visit ASAM

Have you ever wondered why some people seem to thrive on certain diets while others struggle to find the right balance? The answer might lie in our genes. Nutrigenomics is the study of how our individual genetic makeup interacts with the food we eat, influencing everything from our metabolism to nutrient absorption to our overall well-being. In this episode we'll explore this interaction and explain how you may benefit by “eating according to your genes”.  Image by Gerd AltmanShownotes: yournutritionprofs.com Do you have a nutrition question you'd like us to answer? Let us know! Contact Us on our website or any of the following ways:yournutritionprofs@gmail.comYouTubeInstagram Facebook

In this week's Everything Epigenetics episode, I speak with Dr. Toinét Cronjé about what epigenetics can do for the field of epidemiology. Epidemiology is the study of the distribution and determinants of health-related states or events in populations and the application of this study to control health problems. By studying epigenetics and epidemiology in tandem, Dr. Cronjé seeks to understand patterns of diseases in populations, identify risk factors, and develop strategies to prevent or control health issues.More specifically, Dr. Conjé researches epigenetics in understudied populations including the association between DNA methylation and noncommunicable diseases and how DNA methylation clocks perform in these groups.By making the most of the data we have available at the moment (from high-income countries) and of opportunities provided to researchers like herself to work at leading universities like the University of Copenhagen, she hopes that we will get closer to finding the tools to ease the burden on the research communities in low and middle income countries (LMICs). If we can truly start to investigate data from LMICs can you imagine the richness of the information we will unearth?Many of the questions that we are struggling with will be easier to address if we have more diversity in research data sets (e.g. genetics, cultural, dietary, and environmental), as rich (diverse) data sets allow researchers to see more angles to approach their questions from that they might not have been able to see before.Dr. Cronjé's hope is to develop blood-based screening tools for a disease. Only then, when disease screening is accessible to all (e.g. through a blood test instead of intensive and invasive procedures) will we actually know what proportion of populations around the world actually suffer from diseases like these.Using that as a starting block we can finally proceed to addressing stigma and improving care.In this episode of Everything Epigenetics, you'll learn about: Toinét's unique backgroundOMIC epidemiologyWhat epigenetics does for epidemiology The importance of biobanks What we can tell you about yourself when investigating the epigenome using an archived sample from a biobankWhy it's important to research understudied populations What we can learn from low and middle income countriesWhat the research community is missing out on by not studying these groupsNoncommunicable diseases (NCDs)The association between DNA methylation and NCDsThe urban-rural divide which provides a unique opportunity to investigate the effect of the combined presence of multiple forms of environmental exposure on DNAm and the related increase in disease riskToinét's study on “Comparison of DNA methylation clocks in black South African men”Epigenetic age acceleration in the cardiometabolic disease among migrant and non-migrant African populationsAn editorial Toinét wrote in late November 2021 titled “Could unlocking methylation-based blood cell counts revolutionize epidemiology?”The current challenges in epigenetics that should be addressed in future workToinét's next epigenetic-based project Support the showThank you for joining us at the Everything Epigenetics Podcast and remember you have control over your Epigenetics, so tune in next time to learn more about how.

Get in the know about female bioidentical hormone replacement therapy! therapy:https://www.udemy.com/course/draft/5505730/?referralCode=C418EDF9C393C5716D9EDiscover how your exposome—the sum of all your life's exposures—shapes your genetic expression and, in turn, your health. You can direct your genetic expression by controlling your exposome, making lifestyle changes that profoundly influence your health outcomes. From nutrition to stress management, exercise, and more, learn how to upgrade your operating system for a healthier, more vibrant life. Your health and longevity are worth the investment, and this episode provides the guidance you need to age with confidence and embrace the future with enthusiasm.My Website: www.heatlhcouragecollective.comExposome Journal Article: https://pubmed.ncbi.nlm.nih.gov/21081972/

Glenn Murphy is the Director of Communications at Tune Therapeutics, a company that's seriously pushing the envelope in medical innovation with its focus on epigenetics.Tune Therapeutics is revolutionizing gene therapy by using targeted epigenetic modulation to fine-tune gene expression. If you're not entirely sure what that means, keep listening—it's a fascinating and, I believe, critical innovation in healthcare. Tune is breaking free from the limitations of traditional gene and cell therapies by developing solutions for even the most challenging diseases.In addition to his role at Tune, Glenn is the founder and Chief Instructor at NC Systema, a unique training system that blends martial arts, yoga, massage, and meditation. He's also the founder of StressProof, offering resilience training workshops and group retreats for stress management.On the writing front, Glenn is an accomplished author with more than 25 popular science titles to his name, covering topics from astronomy and anatomy to ecology and zoology. Among these are the children's hits "Why is Snot Green?" and "Will Farts Destroy the Planet?"In today's episode, we'll delve into the groundbreaking work Tune Therapeutics is doing in the realm of epigenetics and also hear Glenn's unique tips on communicating complex scientific topics to a broad range of stakeholders.Additionally, we'll explore how the resilience and stress management techniques Glenn has mastered serve him in his corporate work.Without further ado, please give a warm welcome to Glenn Murphy, Director of Communications at Tune Therapeutics.-----Produced by Simpler Media

In this episode of the Epigenetics Podcast, we caught up with Björn Schumacher from the Institute for Genome Stability in Ageing and Disease at the University of Cologne to talk about his work on DNA damage in longevity and ageing. In this episode Björn Schumacher discusses his research on DNA repair and its impact on ageing. We explore his insights on the effects of DNA damage on transcription, the importance of studying development, and the role of histone modifications. We also discuss paternal DNA damage inheritance and the DREAM complex as a master regulator of DNA repair. The lab's goal is to enhance somatic DNA repair for healthier ageing and disease prevention.   References Schumacher, B., van der Pluijm, I., Moorhouse, M. J., Kosteas, T., Robinson, A. R., Suh, Y., Breit, T. M., van Steeg, H., Niedernhofer, L. J., van Ijcken, W., Bartke, A., Spindler, S. R., Hoeijmakers, J. H., van der Horst, G. T., & Garinis, G. A. (2008). Delayed and accelerated aging share common longevity assurance mechanisms. PLoS genetics, 4(8), e1000161. https://doi.org/10.1371/journal.pgen.1000161 Ermolaeva, M. A., Segref, A., Dakhovnik, A., Ou, H. L., Schneider, J. I., Utermöhlen, O., Hoppe, T., & Schumacher, B. (2013). DNA damage in germ cells induces an innate immune response that triggers systemic stress resistance. Nature, 501(7467), 416–420. https://doi.org/10.1038/nature12452 Wang, S., Meyer, D. H., & Schumacher, B. (2023). Inheritance of paternal DNA damage by histone-mediated repair restriction. Nature, 613(7943), 365–374. https://doi.org/10.1038/s41586-022-05544-w Bujarrabal-Dueso, A., Sendtner, G., Meyer, D. H., Chatzinikolaou, G., Stratigi, K., Garinis, G. A., & Schumacher, B. (2023). The DREAM complex functions as conserved master regulator of somatic DNA-repair capacities. Nature structural & molecular biology, 30(4), 475–488. https://doi.org/10.1038/s41594-023-00942-8   Related Episodes Effects of Environmental Cues on the Epigenome and Longevity (Paul Shiels) Transposable Elements in Gene Regulation and Evolution (Marco Trizzino) Epigenetic Clocks and Biomarkers of Ageing (Morgan Levine)   Contact Epigenetics Podcast on Twitter Epigenetics Podcast on Instagram Epigenetics Podcast on Mastodon Active Motif on Twitter Active Motif on LinkedIn Email: podcast@activemotif.com

Guests: Dr. Jimena Laporta, University of Wisconsin-MadisonCovering the topic of Fetal Hyperthermia, Dr. Jimena Laporta of the University of Wisconsin is the second podcast at the 2022 Tri-State Dairy Conference. This makes up part two of the conference series.Heat stress is known to be a significant issue for dairy cattle with both global temperatures and sensitivity of dairy cattle to heat rising. Dr. Laporta adds that negative effects of heat stress last for multiple generations and lactations. 1:16While heat stress affects all cattle, Dr. Laporta focuses on dry cows and their offspring, to provide a more holistic view of its effects. Beginning with the dry cow, she notes that heat stress lessens milk production, as it derails involution and redevelopment. 3:59Epigenetics play a role in fetal development in the dry cow - fetal hyperthermia creates changes in the DNA of the fetus, altering the epigenome. 11:22What are the effects of fetal hyperthermia short term and long term, as well as across generations?Dr. Laporta details many short term hallmarks of prenatal heat stress: the dam experiences a reduction in gestation length leading to a premature calf that has organ alterations, less of an immune response, less feed intake, and a higher core body temperature. 16:31Analyzing a large data set of cattle affected by fetal hyperthermia, Dr. Laporta finds long term effects. The daughters had lower survival rates and less production each lactation, which carried over to the next 2-3 generations. Heat stress effects cost the dairy industry $1.4 billion. 23:08Turning her focus to the molecular signature of heat stress, Dr. Laporta discusses her findings from inspecting a mammary gland, concluding that heat stress causes a lower cell proliferative capacity and negatively impacts protein synthesis. Both lead to compromised milk storage and synthetic capacity. 29:28Wrapping up, Dr. Laporta states that heat stress negatively affects growth, organ development, immune function, survival, longevity, and milk yield for multiple generations. However, she believes that management and nutritional intervention can reduce such effects. 36:58Please subscribe and share with your industry friends to bring more people to join us around the Real Science Exchange virtual pub table.  If you want one of our new Real Science Exchange t-shirts, screenshot your rating, review, or subscription, and email a picture to anh.marketing@balchem.com. Include your size and mailing address, and we'll get a shirt in the mail to you.

In this can't-miss episode, Buck engages in a riveting conversation with the Dr. Joel Rothman, the Founding Director at UCSB's Center for Aging and Longevity Studies (CALS). Prepare to be transported into the cutting-edge world of scientific discoveries that are reshaping our understanding of aging, potentially unlocking the secrets to unprecedented human longevity.  This is only the beginning! Be sure to catch the continuation of this talk in episode 33, where we delve even deeper into the groundbreaking breakthroughs at the frontier of aging research including the research being done at CALS. 00:02:24 - The Science of Aging: A Deeper Dive 00:04:34 - The Human Lifespan 00:07:04 - The Different Lifespans of Organisms 00:09:12 - Aubrey de Grey Longevity Escape Velocity 00:12:27 - The Brain and Aging 00:13:47 - David Sinclair's Book Lifespan 00:14:23 - The Role of Epigenome in Aging 00:19:10 - Genes and Epigenome 00:20:41 - DNA Methylation and Chromosome Structure 00:22:02 - Information Theory of Aging 00:24:14 - Proteostasis or removal of defective proteins 00:26:17 - The Horvath Clock and Biological Clocks 00:30:50 - Epigenome Reset 00:33:53 - Yamanaka Factors  00:37:00 - Extending Healthspan through Cocktails 00:41:44 - Challenges in Drug Development

Buck discusses Yamanaka Factors and recent experiments where a team led by David Sinclair was successful in reversing cellular age applying the concepts in an experiment. 00:00:02 - Is it possible to stop or even reverse the aging process? 00:01:48 - 2012 research by Shinya Yamanaka - Yamanaka Factors  00:02:50 - Pluripotent stem cells 00:03:08 - Revolutionary discovery for the world of regenerative medicine  00:03:28 - Salk Institute study using mice with progeria 00:03:55 - Doxycycline and improvements in signs of aging 00:04:26 - David Sinclair's research to regenerate optic nerves in mice to restore vision 00:04:49 - David Sinclair's book on aging research called Lifespan 00:05:20 - Epigenome and the aging process 00:06:15 - Horvath lab and using Yamanaka factors to reset epigenetic clocks in rats

In this edition of Ask The Doctor Executive Producer asks Buck viewer questions and some of his own. Discussed is continuous glucose monitoring for non-diabetics, cardiac arrest in young athletes, effectiveness of vibrating plates, human growth hormones, jet lag and melatonin. This is Part 2. Listen to episode 24 to hear part 1. 00:01:31 - Question about taking naps to make up for not enough sleep 00:03:06 - REM Sleep and Deep Non-REM Sleep 00:11:54 - Shift work is very detrimental to to health 00:13:11 - Question about reversing aging in cells 00:13:29 - David Sinclair's book Lifespan 00:15:30 - Stem cells and aging 00:17:22 - Genetically mutated rodents with Progeria and  the Yamanaka Factor 00:21:59 - Methylation and the Epigenome 00:22:37 - Biological clocks and changes in the Epigenome 00:23:20 - Sinclair's study on using a drug cocktail to reverse the cellular aging patterns in aged human cells

Episode Description: Jocelynn Pearl, a life scientist, podcast host, and advocate for decentralized science, joins Karl and Erum to discuss the future of biotech and the exciting developments happening in the field. Jocelynn shares her experiences in gene editing, specifically with zinc fingers and TALENs, and how the advent of CRISPR has revolutionized the field. She also highlights the significance of epigenome editing and its potential for treating diseases. Jocelynn discusses the concept of decentralized science and its impact on scientific publishing and collaboration. They conclude with a discussion on the future of biotech, where advancements in therapeutics are expected to lead to significant improvements in patient care. Grow Everything brings to life the bioeconomy when hosts Karl Schmieder and Erum Azeez Khan share stories from the field and interview leaders and influencers in the space.  Life is a powerful force and it can be engineered. What are we creating? Learn more at www.messaginglab.com/groweverything Topics Covered: 00:00:00 Discussing Climate Change and Lab-grown Food: Possible Relief for Global Farmers 00:01:24 Unpacking the Benefits and Common Concerns About Lab-grown Food 00:03:56 Addressing Antibiotics in Livestock and the Impact on Grocery Prices 00:05:10 Exploring the Disparity in Subsidies: The Overemphasis on Fossil Fuel and Highways Over Trains 00:07:26 The Promise of Maglev Trains and Quantum Computing: A Peek Into the Future 00:11:35 Bridging Biology and Technology: An Insight into Biotech Consulting 00:14:32 Speculations on Extraterrestrial Contact: Is It Around the Corner? 00:16:19 Women in Leadership: Reflecting on a Three-Year Journey of Empowering Narratives 00:19:48 The Advent of CRISPR: A Landmark in DNA Editing Revolution Since 2010 00:21:50 Unraveling the Role of Epigenome Editing in Disease Therapeutics 00:23:36 The Epigenetic Approach: Modulating Gene Expression Without DNA Cleavage 00:25:24 Enhancing Human Performance: The Untapped Potential of the Epigenome 00:27:14 The Metformin Study: A Crowdfunded Initiative to Understand Population-wide Effects 00:31:10 The Dawn of Decentralized Science: Envisioning the Future Beyond Regulatory Boundaries 00:33:28 Blockchain Meets Science: A Potential Upheaval in Scientific Publishing 00:37:34 Enhancing Drug Development with Advanced Computational Tools and Protein Structure Prediction 00:39:58 The Biotech Horizon: Predictions and Insights from an Industry Expert 00:42:05 The Rise of Targeted Therapeutics: A New Era in Drug Discovery 00:44:54 A Journey Through Time: Memorable Milestones in Challenging Scientific Careers 00:48:03 Jocelynn's Horticultural Hobby: A Deep Dive into House Plants and Avocado Trees 00:50:23 Seattle's Growing Oasis: Figs, Lavender, Vegetables, and Family Bonds 00:54:03 The 'Grow Everything' Hotline and the Passion for Green Living Episode Links: Jocelynn Pearl on LinkedIn World Farmers' Organization - Anti Lab-grown food statement Northeast Maglev Trains LabDAO Lady Scientist Podcast Tune Therapeutics Venture City on Youtube - Mars timelapse  Astera Institute - Unblocking Scientific Publishing Golden Age of Medicine - New York Times “For Blood and Money: Billionaires, Biotech, and the Quest for a Blockbuster Drug” by Nathan Vardi.  Chasing My Cure by David Fajgenbaum Call or Text the Grow Everything Hotline:  +1 804-505-5553 Have a question or comment? Message us here: Instagram / TikTok / Twitter / LinkedIn / Youtube / GrowEverything website Email: groweverything@messaginglab.com Support here: Patreon Music by: Nihilore Production by: Amplafy Media --- Send in a voice message: https://podcasters.spotify.com/pod/show/messaginglab/message

Can you reverse ageing? We have Chris Mirabile on to share his brain tumour survival journey and what influences his passion for his work around ageing. As he predicts the potential causes of his brain tumour, he speaks about epigenetics, the environmental influences on gene expression, and how we can live longer and healthier lives by addressing nutrient deficiencies, meal timings and other behaviours. Then, he distinguishes between biological and chemical age, identifying the differences in measuring the different age types and why biological age is important to consider, in reference to genetic clocks. Finally, he discusses the relationship between biological age and reproductive health. Let's dive into how we can manipulate our environment to reverse your biological age! Fuel every system within the body and the brain with ⁠⁠⁠LMNT⁠⁠⁠! Keep yourself hydrated on a cellular level by replenishing the sodium, potassium and magnesium that our body needs for basic cellular processes like nerve signalling, smooth muscle contractions, unnecessary fatigue, aches and pain, brain fog, and recovery! Get a free gift with every purchase and try some new flavours as you stay hydrated! (affiliate link). ⁠Adapting High Intensity for Every Body⁠⁠. DocJen, a doctor of physical therapy, and Jill Miller, a Myofascial expert, come together to bridge the gap between post-rehabilitation and highly functional fitness. Your PT isn't gonna teach this to you once you finish your rehab and your coach may not have the kinesiological tools to regress speed/intensity/intervals to a level that's beneficial for your longevity. Who better than Jen and Jill to share with you the Science of Rolling & HIIT and best practices tailored for YOU! This program combines decades of clinical and industry expertise in the worlds of Physical Therapy, mobility, fascia science, HIIT (high-intensity interval training) and regeneration in a mash-up that helps bodies at any age and stage of injury or fitness to prepare their bodies for a successful high-intensity fitness program.   You'll be pampered and prepared with evidence-backed self-myofascial release strategies and learn to integrate your joints, muscles and soft tissues so that intensity will help you rather than harm.  You'll ignite your body and brain's tactile communication system known as proprioception so that you can better inhabit the shapes of acceleration and decelartion that HIIT targets.  You'll reap the benefits of heart-pounding movement while keeping your joints safe and supple. You'll also learn breath control and soft tissue recovery tactics that hasten deep sleep and bring you through robust adaptation cycles that gift you a better tomorrow. What You Will Learn In This Interview with Chris Mirabile 02:22 - What drove Chris's passion 06:38 - Potential causes of Chris's brain tumour 08:36 - Antagonistic pleiteopy  11:45 - What we can do to live a longer and healthier life: deficiencies, meal timing, 24:27 - The importance of micronutrients and longevity 25:54 - How biological age is measured and how it differs from chronological age 31:09 - How can we make biological age important to individuals? 37:05 - Epigenome patterns with ageing 38:54 - Biological age and reproductive health/fertility 41:55 - Learn more from Novus Labs   To learn more about Chris Mirabile⁠ and view full show notes, please visit the full website here:⁠⁠⁠⁠⁠⁠⁠⁠ ⁠⁠ht⁠tps://www.docjenfit.com/podcast/episode311⁠⁠⁠⁠⁠⁠ Thank you so much for checking out this episode of The Optimal Body Podcast. If you haven't done so already, please take a minute to⁠⁠⁠⁠⁠⁠⁠ subscribe⁠⁠⁠⁠⁠⁠⁠ and leave a quick rating and review of the show! --- Send in a voice message: https://podcasters.spotify.com/pod/show/tobpodcast/message

Do you know that supplementing NAD or glutathione with frequent IVs might be hurting your cell's ability to adapt? Join Dr. Jeffrey Gladden, Steve Reiter and Dr. Seeds in this episode of the Gladden Longevity Podcast. Dr. Seeds is a board-certified orthopedic surgeon practicing medicine for over 27 years and the Founder and Medical Director of the Seeds Scientific Research & Performance Mastermind. He has been honored at the NFL Hall of Fame for his medical expertise and in treating professional athletes. He serves as Professional Medical Consultant for the NHL, MLB, NBA, and NBC's Dancing with The Stars. Dr. Seeds is also a medical researcher and continues to write and publish in the NIH and other medical journals. He is also the author of Peptide Protocols Vol.1, the world's first handbook about peptides written for practitioners. Today at the Seeds Scientific Research and Performance Institute, he is dedicated to bringing Cellular Medicine and the study of Epigenome to the forefront of the medical community through research, training, and improved patient outcomes. His practice is at the Olympic training facility: Spire Institute Geneva, OH, and at the Redox Medical Group, Beverly Hills, CA. This episode discusses how cellular redox is quickly going to become the health goal and how this is where disease, aging, and cancer starts, and that it is also where we can find solutions. As the podcast progresses, they talk about our cell's main job, the balance and the imbalance of oxidation and reduction, and the benefits of achieving cellular redox. They explore various peptides and their ability to maintain homeostasis of redox, improve gut health, decrease anxiety, and aid in recovery after injury or training. Moreover, they touch on the importance of addressing gut health to tackle immune issues and offer dosage recommendations for peptides.   Listen to this episode to learn about making 100 the new 30 and living young for a lifetime!    Dr. Gladden mentions that Seeds was the one that certified him in peptides. (1:15)  Dr. Gladden explains that we make peptides in our bodies. (2:24)  Dr. Gladden welcomes Dr. Seeds. (4:10)  Dr. Gladden explains cellular redox. (6:14)  Dr. Seeds shares that his mission was to introduce people to cellular medicines. (8:09)  Dr. Seeds speaks about making microfilaments in a cell to keep the structure of the cell symmetrical. (10:35)  Dr. Seeds shares that if you're regulating the infrastructure of a cell to keep it at its optimal, and you're keeping the signaling at its optimal, then you're reducing cellular redox issues, and you're reducing problems that create, like fibrosis. (12:40)  Dr. Gladden asks Dr. Seed about the interplay between GHKCU and BPC 157. (15:40)  Dr. Gladden discloses his observations that injuries seem to heal faster with the use of peptides. (18:03)  Dr. Gladden shares that he wakes up feeling 27 every day. (19:50)  Dr. Gladden goes over what being nominated means. (21:25)  Dr. Gladden emphasizes that people could make a case for using BPC on a daily basis. (24:13)  Dr. Seeds says T-regs cells are masters of immune tolerance. (28:00)  Dr. Seeds reveals the discovery of zonulin, which is a toxin from the cellular connection in the bowel. (32:25)  Dr. Seeds advises that people need to focus on the gut with lots of immune issues. (35:15)  Dr. Seeds discloses a peptide that helps with leaky gut. (37:36)  Dr. Seeds speaks about one of the best peptides available that can be used intranasal or subcutaneously. (41:28)  Dr. Seeds reveals that BDNF is a big player in anxiety and depression. (44:10)  Dr. Seeds advises that you must be careful with CMAX because it's more of an activator. (47:40)  Dr. Seeds refers to how working with younger kids is a game changer. (50:25)  Dr. Seeds says there are good and bad aspects of nicotinamide. (54:25)  Dr. Seeds spells out one of the best peptides we have if you know how to use it. (57:00)  Dr. Seeds refers to an incredible peptide that only needs to be used for short periods. (59:00)  Steve announces that Dr. Seeds has a book on peptides and thanks everyone for listening. (1:00:07)           Visit our website, www.gladdenlongevitypodcast.com, for more information on this episode and other episodes as well. Click on the link to let us know what you'd like us to talk about on the podcast too!                      Follow us on social media!                                Instagram: @gladdenlongevity                                Twitter: @gladdenlongevit                                Facebook: @GladdenLongevity                         LinkedIn: @GladdenLongevity    For more information on our practice or how to become a client, visit:   www.gladdenlongevity.com  Call us: 972-310-8916  Or email us: info@gladdenlongevity.com    To learn more about Dr. Seeds and his work, check out the following:    https://seeds.md/  For health practitioners: ssrpinstitute.org  For health enthusiasts: redoxmedicalgroup.com  IG: @williamaseedsmd @ssrpinstitute @redoxmedicalgroup    DISCOUNT:   Podcast10 (10% off your purchase at the Gladden Longevity Supplement shop (https://gladdenlongevityshop.com/) 

In this episode of the Epigenetics Podcast, we caught up with Paul Shiels from the University of Glasgow to talk about his work on the effects of environmental cues on the epigenome and longevity. Paul Shiels and his team focus on the question on how age related health is influenced by the environment. Factors like the socio-economic position, nutrition, lifestyle and the environment can influence the microbiome and the inflammation burden on the body which in turn can alter individual trajectories of ageing and health. The lab also tries to understand the epigenetic, molecular and cellular mechanisms that link the exposome to chronic age related diseases of older people. They have shown that (1)  imbalanced nutrition is associated with a microbiota-mediated accelerated ageing in the general population, (2) a significantly higher abundance of circulatory pathogenic bacteria is found in the most biologically aged, while those less biologically aged possess more circulatory salutogenic bacteria with a capacity to metabolise and produce cytoprotective Nrf2 agonists, (3) those at lower socioeconomic position possess significantly lower betaine levels indicative of a poorer diet and poorer health span and consistent with reduced global DNA methylation levels in this group.   References Harris, S. E., Deary, I. J., MacIntyre, A., Lamb, K. J., Radhakrishnan, K., Starr, J. M., Whalley, L. J., & Shiels, P. G. (2006). The association between telomere length, physical health, cognitive ageing, and mortality in non-demented older people. Neuroscience Letters, 406(3), 260–264. https://doi.org/10.1016/j.neulet.2006.07.055 Paul G. Shiels, Improving Precision in Investigating Aging: Why Telomeres Can Cause Problems, The Journals of Gerontology: Series A, Volume 65A, Issue 8, August 2010, Pages 789–791, https://doi.org/10.1093/gerona/glq095 Mafra D, Ugochukwu SA, Borges NA, et al. Food for healthier aging: power on your plate. Critical Reviews in Food Science and Nutrition. 2022 Aug:1-14. DOI: 10.1080/10408398.2022.2107611. PMID: 35959705. Shiels PG, Stenvinkel P, Kooman JP, McGuinness D. Circulating markers of ageing and allostatic load: A slow train coming. Practical Laboratory Medicine. 2017 Apr;7:49-54. DOI: 10.1016/j.plabm.2016.04.002. PMID: 28856219; PMCID: PMC5574864.   Related Episodes Transposable Elements in Gene Regulation and Evolution (Marco Trizzino) Epigenetic Clocks and Biomarkers of Ageing (Morgan Levine) Aging and Epigenetics (Peter Tessarz)   Contact Epigenetics Podcast on Twitter Epigenetics Podcast on Instagram Epigenetics Podcast on Mastodon Active Motif on Twitter Active Motif on LinkedIn Email: podcast@activemotif.com

A new research paper was published in Aging (Aging-US) Volume 15, Issue 5, entitled, “Age-related methylation changes in the human sperm epigenome.” Advanced paternal age is associated with increased risks for reproductive and offspring medical problems. Accumulating evidence suggests age-related changes in the sperm epigenome as one underlying mechanism. In a recent study, researchers Laura Bernhardt, Marcus Dittrich, Andreas Prell, Ramya Potabattula, Charis Drummer, Rüdiger Behr, Thomas Hahn, Martin Schorsch, Tobias Müller, and Thomas Haaf from Julius Maximilians University, Partner Site Göttingen and Fertility Center Wiesbaden performed reduced representation bisulfite sequencing (RRBS) on 73 sperm samples of males attending a fertility center in Germany. “[...] we identified 1,162 (74%) regions which were significantly (FDR-adjusted) hypomethylated and 403 regions (26%) being hypermethylated with age.” There were no significant correlations with paternal BMI, semen quality, or ART outcome. The majority (1,152 of 1,565; 74%) of age-related differentially methylated regions (ageDMRs) were located within genic regions, including 1,002 genes with symbols. Hypomethylated ageDMRs were closer to transcription start sites than hypermethylated DMRs, half of which reside in gene-distal regions. In this and conceptually related genome-wide studies, so far 2,355 genes have been reported with significant sperm ageDMRs, however most (90%) of them in only one study. The 241 genes which have been replicated at least once showed significant functional enrichments in 41 biological processes associated with development and the nervous system and in 10 cellular components associated with synapses and neurons. This supports the hypothesis that paternal age effects on the sperm methylome affect offspring behavior and neurodevelopment. The researchers found it interesting to note that sperm ageDMRs were not randomly distributed throughout the human genome; chromosome 19 showed a highly significant twofold enrichment with sperm ageDMRs. Although the high gene density and CpG content have been conserved, the orthologous marmoset chromosome 22 did not appear to exhibit an increased regulatory potential by age-related DNA methylation changes. “Collectively, our data support the conclusion that age-induced methylation changes in the sperm epigenome contribute to the increased offspring disease susceptibility for neurodevelopmental disorders.” DOI: https://doi.org/10.18632/aging.204546 Corresponding Author: Thomas Haaf - thomas.haaf@uni-wuerzburg.de Keywords: ART outcome, DNA methylation, male germ cells, paternal age effect, human sperm epigenome Sign up for free Altmetric alerts about this article: https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204546 Keywords - aging, ART outcome, DNA methylation, male germ cells, paternal age effect, human sperm epigenome About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Visit our website at https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ MEDIA@IMPACTJOURNALS.COM

How old are you? A simple question, with a simple answer, right? Wrong.   In this episode, we chat with the brilliant Ryan Smith, co-founder and VP of TruDiagnostic.   TruDiagnostic is a global leader in tests that measure our epigenome and uncover what it tells us about biological age. At the risk of oversimplifying something quite complex, biological age describes the real rate at which your body is ageing and there are various ways to measure it.   Ryan invited us to test out their TruAge test. We did the required blood spot tests, and sent them off and in this episode, we talked to Ryan about the results. Am I ageing faster, or slower than my biological age?  And what does it mean? I'm not telling you here, take a listen and find out.   Without giving anything away, seeing my results from this test has been fascinating. It has inspired me to maintain lots that I do and it has motivated me to explore new habits in my longevity quest. Epigenome testing is still in its infancy in the longevity field, but there is no doubt that this will be the future of how we look at health optimisation.   We have a 12% discount we can pass on if you want to explore your own biological age. Use this link to make sure you get the 12% discount for TruDiagnostic  

The approach removes methyl tags from the gene and shields it from other silencing factors without changing the gene itself, raising hopes for a new treatment.

The approach removes methyl tags from the gene and shields it from other silencing factors without changing the gene itself, raising hopes for a new treatment.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.09.19.508525v1?rss=1 Authors: Choi, E. Y., Franco, D., Stapf, C. A., Gordin, M., Chow, A., Cover, K. K., Chandra, R., Lobo, M. K. Abstract: Substance use disorder is a debilitating chronic disease and a leading cause of disability around the world. The nucleus accumbens (NAc) is a major brain hub that mediates reward behavior. Studies demonstrate exposure to cocaine is associated with molecular and functional imbalance in two NAc medium spiny neuron subtypes (MSNs), dopamine receptor 1 and 2 enriched D1-MSNs and D2-MSNs. Our previous reports showed that repeated cocaine exposure induced transcription factor early growth response 3 (Egr3) mRNA in NAc D1-MSNs, while reducing it in D2-MSNs. Here, we report our findings of repeated cocaine exposure inducing cell subtype specific bidirectional expression of the Egr3 corepressor NGFI-A-binding protein 2 (Nab2). Using CRISPR activation and interference (CRISPRa and CRISPRi) tools combined with Nab2 or Egr3 targeted sgRNAs, we mimicked these bidirectional changes in Neuro2a cells. Furthermore, we investigated D1-MSN and D2-MSN subtype specific expressional changes of histone lysine demethylases Kdm1a, Kdm6a and Kdm5c in NAc after repeated cocaine exposure. Since Kdm1a showed bidirectional expression patterns in D1-MSNs and D2-MSNs, like Egr3, we developed a light inducible Opto-CRISPR-KDM1a system. We were able to downregulate Egr3 and Nab2 transcripts and cause bidirectional expression changes in D1-MSNs and D2-MSNs similar to cocaine exposure in Neuro2A cells. In contrast, our Opto-CRISPR-p300 activation system induced the Egr3 and Nab2 transcripts and caused bidirectional transcription regulations in D1-MSNs and D2-MSNs. Our study sheds light on the expression patterns of Nab2 and Egr3 in specific NAc MSN subtypes in cocaine action and uses CRISPR tools to further mimic these expression patterns. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer

Despite public market investors shying away from preclinical companies amid biotech's bear market, large biopharmas have ramped up their deal making for early-stage assets and technologies and are willing to pay for access to new modalities, says BioCentury's Stephen Hansen on the latest BioCentury This Week podcast. Hansen and colleagues also discuss the implications of FDA's approval of gene therapy Zynteglo from bluebird bio Inc., and the latest advances and leaders in the field of epigenome editing.

Imagine that you are a college student, whose professors all magically decided to give exams and projects due on the same date. For some reason, you procrastinated until the last minute, and now you need to pull an all-nighter at the library. You begrudgingly head to the fourth floor of the library, prepared to stay awake with a bag full of your favorite candy bars and snacks, a Venti Starbucks iced coffee, and a couple cans of Red Bull. You finally leave the library with sleepy eyes just as the sun slowly rises above the horizon. On the actual exam, you feel very tired and have trouble concentrating. A couple days later, you get your not-so-great grade back for your exams and projects, and you make a promise to yourself that you will never make the same mistake. But two weeks later, you end up doing it again a couple weeks later. This all sounds too familiar, right?

The words bonding and attachment are common words, but what is the deeper meaning behind those words for new parents and their newborns or yet-to-be born babies?  How can parents connect with their newborn in utero?  How will the attachment before and after the baby is born affect the epigenomes, brain development, and future health of their little one?  Laurel will take us on a fascinating dive into this topic to help us translate this information to our patients, students, and clients so that more new parents will understand the benefits of attachment to their new babies.  Laurel Wilson, IBCLC, RLC, BSc, CLE, CCCE, CLD is a TEDx and international speaker, pregnancy and lactation specialist, consultant, educator, and author. Laurel is the co-author of two books, The Attachment Pregnancy and The Greatest Pregnancy Ever; original editor of The CAPPA Lactation Educator Manual; as well as a contributing author to Round the Circle: Doulas Talk About Themselves. Her passion is blending today's recent scientific findings with mind/body/spirit wisdom to highlight the magnitude and importance of the perinatal period. Spending 17 years as Executive Director for Lactation Programs for the Childbirth and Postpartum Professionals Association formed the foundation of her inquiry into the science of human milk. She has acted and still acts in many capacities locally and nationally promoting the belief that the journey into parenthood is a life-changing rite of passage that should be deeply honored and celebrated.  Listen and Learn:  The physiological and emotional process of bonding and attachment that occurs during birth & beyond  What is epigenetics, epigenome, and microbiome and how are they connected?  How epigenetics work in a human is based on the external reality of that person's experiences How the first 1,000 days of a baby's life and their external reality impacts their organ systems How most diseases are not DNA related but rather influenced by epigenetic impact What impact chronic stress, including weathering, has on future health How to teach parents to move away from stress when possible  What full engagement means during pregnancy    Resources & Mentions:  https://motherjourney.com/index.html (Laurel's website with many more resources)  Association for Prenatal and Perinatal Psychology and Health   Kindred – One Family, One World   Related Products from InJoy:  Understanding Pregnancy  Understanding Breastfeeding Understanding Your Newborn Understanding Fatherhood 

Dr. Amber Salzman, Ph.D. is Chief Executive Officer and Director of Epic Bio (https://epic-bio.com/), a fascinating therapeutic epigenome editing startup, developing therapies to modulate gene expression at the level of the epigenome, which just recently emerged from stealth mode with a $55 million funding round. Dr. Salzman has more than 30 years of experience in the pharmaceuticals industry. Before joining Epic Bio, Dr. Salzman served as the president and CEO of Ohana Biosciences, pioneering the industry's first sperm biology platform. Before Ohana, she served as the president and CEO of Adverum Biotechnologies and was a co-founder of Annapurna, SAS, where she served as President and CEO before its merger with Avalanche Biotechnologies to become Adverum. In that role, she saw the company's stock price double. Dr. Salzman began her career as a member of the GlaxoSmithKline (GSK) research and development executive team, where she was responsible for operations in drug development across multiple therapeutic areas, overseeing global clinical trials with over 30,000 enrolled patients, managing 1,600 employees and a $1.25B budget. Following her time at GSK, Dr. Salzman served as the CEO of Cardiokine, a pharmaceutical company that developed treatments for the prevention of cardiovascular diseases and saw the successful sale of the company to Cornerstone Therapeutics. Dr. Salzman currently serves on the Osler Diagnostics (UK) and AviadoBio (UK) Boards. Dr. Salzman received her bachelor's degree from Temple University in computer science and holds a Ph.D. in mathematics from Bryn Mawr College. In addition to advocating for patients living with rare diseases, Dr. Salzman leads the Stop ALD Foundation, a non-profit medical research foundation focused on developing novel gene therapies for adrenoleukodystrophy (ALD).

This week, please join author Ambarish Pandey and Editorialist Linda Peterson as they discuss the article "Frailty Status Modifies the Efficacy of Exercise Training Among Patients with Chronic Heart Failure and Reduced Ejection Fraction: An Analysis from the HF-ACTION Trial" and the editorial "Heart Failure With Reduced Ejection Fraction (HFrEF): ‘The Importance of Being Frail.'" Dr. Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast, summary, and backstage pass to the journal and its editors. We're your co-hosts. I'm Dr. Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore. Dr. Greg Hundley: And I'm Dr. Greg Hundley, associate editor director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Well, Carolyn, this week's feature article, Heart Failure Reduced Ejection Fraction in Evaluating the Efficacy of Exercise Training. But guess what? It appears it may be more efficacious in those that have high Frailty Index scores, as opposed to those that may not. But before we get to our feature discussion, let's grab a cup of coffee and go through some of the other articles in the issue. Would you like to go first? Dr. Carolyn Lam: I would love to, and this first paper is one that defines epigenetic biomarkers of lifelong cardiovascular health exposure and really contributes to our understanding of their roles in cardiovascular disease development. First though, a little quiz for Greg. So, Greg, what does DNA methylation mean to you? Dr. Greg Hundley: Well, Carolyn, DNA methylation. So, what I understand is these methyl groups get involved with our DNA and actually affect change over time that leads to phenotypic expression of, maybe, new traits. But I don't know. Maybe I'm not quite up to date. Dr. Carolyn Lam: Oh, you're perfect. Indeed, DNA methylation is a widely characterized epigenetic modification, which means exactly as you said. It's a regulatory modification to our DNA induced by environmental exposures and can affect gene expression. And this is the topic of today's paper by Doctors Zheng, Hou, and Lloyd-Jones from Northwestern University Feinberg School of Medicine and their colleagues. So, what they did is they studied blood DNA methylation at over 840,000 methylation markers measured twice over five years in participants of the CARDIA study. Epigenome-wide association analyses on a clinical cumulative cardiovascular health score were then performed in both CARDIA and compared in the Framingham Heart Study. Dr. Carolyn Lam: The authors identified 45 midlife DNA methylation markers associated with clinical cardiovascular health metrics, such as body mass index, blood pressure, blood glucose, and total cholesterol longitudinally measured since young adulthood. The methylation markers were located in genes involved in lipid metabolism, insulin secretion, and cytokine production, which could not be fully attributed to genetic factors. So, they proposed and validated in summary a methylation-based risk score to promote a personalized cardiovascular disease risk evaluation beyond traditional cardiovascular risk factors. Dr. Greg Hundley: Oh, wow, Carolyn. Interesting, a methylation-based risk score to promote personalized cardiovascular disease risk evaluation. Wow! That's really exciting. Dr. Greg Hundley: Well, I'm going to go to the world of preclinical science, and just like last week where we had a really nice article on myocardial regeneration, this week, we've got another. And so, Carolyn, early neonates of both large and small mammals are able to regenerate the myocardium through cardiomyocyte proliferation for only a very short period after birth. This myocardial regenerative capacity declines in parallel with withdrawal of cardiomyocytes from the cell cycle in the first few postnatal days. No mammalian species examined to date has been found capable of a meaningful regenerative response to myocardial injury later than one week after birth. Dr. Carolyn Lam: Interesting. Now, I see that these investigators worked with possums. Could you tell me why they did that, and what did they find, Greg? Dr. Greg Hundley: Right, Carolyn. So, this work was led by Dr. Wataru Kimura from the RIKEN Center for Biosystems Dynamic Research and their colleagues. The reason they studied possums, so the marsupial possum maintains cardiomyocyte proliferation and a capacity for myocardial regeneration for at least two weeks after birth. Remember we stated before, all the other mammalian species, it's only one week after birth. So, this appears to be the longest postnatal duration of such a capacity among mammals examined to date, and AMP kinase signaling was implicated as an evolutionary conserved regulator of mammalian postnatal cardiomyocyte proliferation. Dr. Greg Hundley: And they additionally found that in a separate mouse experiment, the authors noted that the pharmacological inhibition of AMP kinase signaling was sufficient to extend the postnatal window of cardiomyocyte proliferation in neonatal mice, so really exciting work in the area of cardiomyocyte regeneration. Dr. Carolyn Lam: Wow, indeed! And I've learned now about possums. Thank you, Greg. Dr. Carolyn Lam: So, Greg, have you ever asked yourself, what is the frequency, penetrance, and variable expressivity of dilated cardiomyopathy-associated gene variants in the general population? Well, guess what? This next paper addresses just that in more than 18,600 UK Biobank participants who had undergone whole-genome sequencing, ECG, and cardiovascular magnetic resonance imaging. Dr. Greg Hundley: Wow, Carolyn, another really interesting study from the UK Biobank. So, what did they find? Dr. Carolyn Lam: So, this study is from Dr. Chahal from the Center for Inherited Cardiovascular Diseases Wellspan Health in Lancaster, Pennsylvania and colleagues, and they found that approximately one in six of adults with putative pathogenic variants in dilated cardiomyopathy genes exhibited early dilated cardiomyopathy features potentially associated with the genotype. And it's most commonly manifesting with arrhythmias in the absence of substantial ventricular dilation or dysfunction. Dr. Carolyn Lam: Among individuals with putative pathogenic dilated cardiomyopathy gene variants, ECG or CMR-detected early features were nearly four times more common than clinically manifest dilated cardiomyopathy or early features. Over 90% of subjects with these gene variants in dilated cardiomyopathy-associated genes did not have a prior history of dilated cardiomyopathy, and the overall clinical or subclinical penetrance of dilated cardiomyopathy-associated single pathogenic variants was highly variable between genes ranging from zero to 67%. And so, in conclusion, a genotype-first screening approach for dilated cardiomyopathy using a large genetic panel is currently not suitable in the general population due to incomplete understanding of the genetic architecture and reduced penetrance of the associated genes. Dr. Greg Hundley: Very nicely said, Carolyn. Wow! Well, let's take a look and see what's in the mailbag. And first, there's a Research Letter from Professor Huguenard entitled, “Frequency of Screening Detected Intracranial Aneurysms in Patients With Loeys-Dietz Syndrome.” And our own Bridget Kuehn has a really nice piece on Cardiology News. Dr. Carolyn Lam: Nice. There's also an On My Mind paper by Dr. Sattar, McGuire, and Gill entitled, “High-Circulating Triglycerides Are Most Commonly a Marker of Ectopic Fat Accumulation: Connecting the Clues to Advanced Lifestyle Interventions,” and an exchange of letters between Dr. Groothof and myself, Dr. Lam, regarding my article on “Efpeglenatide and Clinical Outcomes With and Without Concomitant SGLT-2 Inhibition in Type 2 Diabetes: An Exploratory Analysis of the AMPLITUDE-O Trial.” Dr. Carolyn Lam: Ah, that was awesome. Well, thanks, Greg. I am so excited to get to the future discussion that you queued us on so well, frailty in heart failure with reduced ejection fraction. Here we go. Dr. Greg Hundley: You bet. Dr. Greg Hundley: Welcome, listeners, to this July 12th, 2022 feature discussion. And we have with us today, Dr. Ambarish Pandey from University of Texas Southwestern Medical Center in Dallas, Texas, and Dr. Linda Peterson, an editorialist for this article from Washington University in St. Louis. Welcome to you both. Well, Ambarish, We're going to start with you. Could you describe for us basically the background information that went into the preparation of your study, and what was the hypothesis that you wanted to address? Dr. Ambarish Pandey: Thanks, Greg, for having me on this, and thanks to Circulation for publishing our article. Yeah, I think the premise for this study stems from the longstanding known benefit of exercise training in patients with heart failure with reduced ejection fraction. Now, that was shown in the HF-ACTION trial, where individuals with chronic stable heart failure with reduced ejection fraction underwent exercise training, and there was demonstrated benefit in quality of life and adjusted analyses. There was a protocol-specified adjusted analysis that did demonstrate improvement in some of the key primary endpoint. Dr. Ambarish Pandey: Based on these results, CMS has approved exercise training and cardiac rehabilitation in patients with chronic stable heart failure with reduced ejection fraction. However, despite this mandate from CMS and generally well-accepted benefits of exercise training in heart failure with reduced ejection fraction, the uptake of exercise training has been pretty low, and there's a lot of heterogeneity in the improvement in outcomes that is associated with exercise training. Dr. Ambarish Pandey: So, we wanted to see whether frailty, which is a well-characterized syndrome of reduced physiologic reserve and impaired homeostatic tolerance to stressors and is common in patients with HFrEF, we wanted to see how frailty modifies the beneficial effects of exercise training in HFrEF. And based on the existing literature and some of the prior works we have done, we hypothesized that individuals who are frail and who have more functional impairments are going to have more targets for improvement in their functional status and thus would be more likely to benefit from exercise training. And we looked at this in the HF-ACTION trial itself and using the Rockwood Frailty Index and the difference in primary outcome and treatment effect of exercise among frail and non-frail individuals. Dr. Greg Hundley: Very interesting, so really sort of a look back in HF-ACTION data. Describe a little bit more for us that study design, and then specifically, what was the study population that you used to test your hypothesis? Dr. Ambarish Pandey: Right. So HF-ACTION was a randomized control trial multi-centered that was sponsored by NHLBI and was conducted in the early 2000s and basically focused on chronic stable patients with heart failure with reduced ejection fraction who have not had a hospitalization in the past six weeks and have ejection fraction less than 35% and class II to IV. And these participants were randomized in one-to-one fashion to getting aerobic exercise training followed by some home-based exercise versus the usual care. Dr. Ambarish Pandey: And in our study, what we looked at was we looked at the effect modification by baseline frailty status on the treatment effect of exercise training. So, we calculated the frailty index, which is a well-established measure of frailty using a Rockwood Index Model, and we stratified patients by frail versus non-frail status based on a Frailty Index cut-off of 0.21, such that higher index identifies more frail participants. And then, we looked at how the treatment benefit of exercise training on different outcomes was differential across the frail and non-frail strata. We looked at qualitative interaction, and we also looked at the Frailty Index, so the continuous variable to assess the benefits of exercise across the spectrum of frailty in the study population. Dr. Greg Hundley: And so, before we get to your study results, how many patients were in your study? Give us an idea of what was the range in age, and then also the composition of sex? How many men? How many women? Dr. Ambarish Pandey: Right, so this is really important because that's addressed to the generalizability of the study. So, the study included around a little over 2,100 participants. The mean age was 59 years. 28% were women, and 32% were self-reported black individuals with chronic stable heart failure. That was the demographic distribution. The age was slightly younger than what you've commonly see in observational studies with heart failure, and that is largely because the study recruited patients who were able to do exercise training and were able to do exercise tests with peak VO2 and peak VO2 peak excess capacity assessment at baseline and follow-up. So, that kind of selected for a slightly younger population. Dr. Greg Hundley: Very nice. And so, what were your study results? Dr. Ambarish Pandey: So our study results are, indeed, pretty interesting. We identified that around 60% of patients with chronic stable heart failure with reduced ejection fraction who were in the trial were actually frail based on the Rockwood Frailty Index Model. And we observed that among the study participants, the exercise training was associated with significant improvement in the primary composite endpoint of all-cause hospitalization or death in frail participants, but not in the non-frail or less fail participants. And there was a significant treatment interaction, such that baseline frailty modified the treatment effect of exercise training for the primary composite endpoint. Dr. Ambarish Pandey: Now, this was largely driven by a significant reduction in all-cause hospitalization among frail individuals who underwent exercise training, and not so much by an effect on mortality. And we did not see a significant difference in the mortality component of the primary composite endpoint across frail versus non-frail status participants. So, in a nutshell, baseline frailty did modify the treatment effect, largely driven by substantial reduction in the risk of all-cause hospitalization among frail participants more than non-frail participants. Dr. Greg Hundley: And before we get to Linda in her interpretation of your study, Ambarish, did you see the same effects in frail men, in frail women? And also, what about in individuals that might be a little older versus those that were perhaps younger? Dr. Ambarish Pandey: That's a really important question, and we were a little bit limited to do further subgroups because we are dealing with around, I think, 2,000 participants and we had frail, non-frail, and we did not do a further subgroup stratification by sex or by age. The age range was rather narrow. It's 58 years plus/minus 13 years, so we didn't really have a lot of older individuals above 75, something like what REHAB-HF Trial has shown in the news, a recent trial. Dr. Ambarish Pandey: We couldn't address the question of whether the effect modification was further modified by sex or age, so I think that's the two-level interaction. But I think that is something that would be interesting to test perhaps in a pool analysis of multiple exercise training studies, which is something we are considering. Dr. Greg Hundley: Thank you. Well, listeners, now we're going to turn to our editorialist, Dr. Linda Peterson, from Washington University in St. Louis, and, Linda, very provocative results here, heart failure reduced ejection fraction. And certainly, we like to go to things like cardiac rehab, but we're hearing this it seemed to make a difference if you were frail versus not frail. Dr. Linda Peterson: Right, I think that's an important distinction here in this article as Ambarish has so eloquently put forth, and it's especially important because other articles have shown in looking at the PARADIGM-HF Study and ATMOSPHERE it appears that one out of two patients with HFrEF are actually frail. And so, the magnitude of these findings and the importance of these findings is highlighted by that study. And this frequency of frailty is roughly double that of community-dwelling adults who are over age 90, so we're thinking of frailty usually as much older adults, but in HF-ACTION, actually, the patients' average age was 60 in the patients with HFrEF. Dr. Linda Peterson: So, there's almost an accelerated aging phenotype we're seeing here in a large proportion of the patients who have HFrEF. I think this has an enormous impact on a lot of the patients that we're seeing with HFrEF, and we should be alerted to looking for frailty and potentially screening for frailty. And I think another highlight of this study is that it points out the importance of frailty because frail patients have a 50% higher risk of hospitalization and death, according to some other studies, particularly one by Faray and their group and also by Yang and their group. Dr. Linda Peterson: And so, it highlights the importance of getting patients who are frail with HFrEF into cardiac rehab or getting them some sort of aerobic exercise training. But paradoxically, frailty is also associated with a lower likelihood of those particular patients on getting into cardiac rehab and also getting on goal-directed medical therapy. And that was shown by Phil Ades and his group. So, I think the importance of these findings by Ambarish and his group are to be commended, and they're very important for a large proportion of our patients with HFrEF. Dr. Greg Hundley: Very nice. Well, let's turn back to Ambarish, and then follow up with Linda. Ambarish, what do you see as the next study that should be performed in follow-up to your study? Dr. Ambarish Pandey: I think that's a great question. And I think we are just beginning to realize the magnitude of impact that frailty has in the care of patients with heart failure. And this goes across the spectrum of ejection fraction, both HFpEF or heart failure with preserved ejection fraction and heart failure with reduced ejection fraction. Indeed, the burden of frailty is higher in patients with heart failure with preserved ejection fraction, and they are more of the accelerated aging phenotype. Dr. Ambarish Pandey: And I think the next study basically should look at a targeted approach to exercise training or category of intervention among patients who are most likely to benefit from it, which would be patients who have a high frailty burden or patients who have HFpEF. I think they go hand in hand when it comes to frailty and HFpEF. So, I think that's the next study to do is to see to what extent we can actually identify and target exercise training in the highest risk individuals who are most likely to benefit from it because that subset of highest modifiable risk is indeed identified by frailty and when you look at other subtypes by HFpEF which has a lot of high frailty burden. Dr. Greg Hundley: And, Linda, from your perspective, what do you see as the next study to be performed in this sphere of research? Dr. Linda Peterson: Yeah, I think this study really provides a springboard for future studies in HFrEF, in particular. One, what hospital interventions can be done in patients to get them moving more, and really assess is there a possibility of different types of exercises to get patients less frail even while they're in the hospital when they're enroute to going home? And then also, how do we have different mechanisms by which we can get more patients into cardiac rehab? Clearly, our national average of getting patients who qualify for cardiac rehab, which is a class I indication is 20% at best, and the aim from the AHA is 70%. Dr. Linda Peterson: There's a big gap there, so interventions looking at implementation and getting patients to cardiac rehab or looking at other types of aerobic exercise training, such as home-based cardiac rehab for patients who don't have a cardiac rehab center next to them, I think the field is wide open for different studies to springboard off of these findings. Dr. Greg Hundley: Very nice. Well, listeners, we want to thank Dr. Ambarish Pandey from University of Texas Southwestern Medical Center in Dallas, Texas, and our editorialist, Dr. Linda Peterson, from Washington University in St. Louis, for bringing us this research study, highlighting that among patients with chronic stable heart failure and reduced ejection fraction, that baseline frailty modified the treatment effect of aerobic exercise training with a greater reduction in the risk of all-cause hospitalization. Dr. Greg Hundley: Well, on behalf of Carolyn and myself, we want to wish you a great week, and we will catch you next week on the run. Speaker 5: This program is copyright of the American Heart Association 2022. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more, please visit ahajournals.org.

As you know, it's my mission to help teach you how to build the MINDSET and SKILLS that will help you live an extraordinary life - and over the last few months I've been working hard behind the scenes to help create a brand-new tool that will help you do that. It's called Kyzen - and I am proud to announce that I will be bringing it to the world later this year to challenge you to empower yourself and accomplish greater things in life. To learn more, join my Discord at http://impacttheory.com/discordBig goals require DISCIPLINE. By it's very nature, discipline requires you to do hard things - and that is a skill you can LEARN. I'm teaching my process to build Ironclad Discipline in a new workshop - you can register at discipline.impacttheory.com!The fountain of youth is a mythical spring that has been the basis of many Hollywood movies and cosmetic marketing campaigns! Our obsession with youth and being young forever has been the source of cosmetic surgery and endless stories of ‘back in my day'.David Sinclair is a Professor in the Department of Genetics and co-Director of the Paul F. Glenn Center for Biology of Aging at Harvard Medical School. As a professor, scientific investigator and co-founder of multiple biotech companies, his knowledge with epigenetics and reverse aging is highly regarded among professional colleagues in the industry. He's appeared on dozens of podcasts, written books, and hosts his own podcast, Lifespan. As a guest on Health Theory the conversations around reverse aging and biological clocks are more than enlightening.Finding the root cause to aging and understanding how diet, exercise, and lifestyle choices impact our aging process puts the power of perspective and knowledge within your control. You don't have to guess or hope for a mythical spring of magical water that holds the secret of youth. You can make a decision everyday to turn back the clock, slow the aging process, and reset your age.SHOW NOTES:0:00 | Introduction to David Sinclair0:12 | Daily Hacks to Slow Aging28:50 | How to Reset Your Age58:43 | This Causes Aging1:32:23 | How to Understand AgingQUOTES:“80% of your longevity and health in old age is controllable and only 20% is dictated by your genes, the genome. The rest is your epigenome that responds to how we live [7:36]“Our livers are much smarter than our eyes and our mouths…” [24:35]“Anything that stresses your body, puts it into a state of shock is good in the long run.” [38:16]“When I boiled it down to its essence I realized aging was a loss of information.” [1:01:58]“That's part of the problem with aging, which is genes getting turned on when they should be kept off for decades, and then cells start to get confused.” [1:14:17]Follow David Sinclair: Website: https://sinclair.hms.harvard.edu/ YouTube: https://www.youtube.com/davidsinclairpodcast Podcast: https://anchor.fm/lifespan Instagram: https://www.instagram.com/davidsinclairphd/ Twitter: https://twitter.com/davidasinclair Facebook: https://www.facebook.com/davidsinclairphd

As you know, it's my mission to help teach you how to build the MINDSET and SKILLS that will help you live an extraordinary life - and over the last few months I've been working hard behind the scenes to help create a brand-new tool that will help you do that. It's called Kyzen - and I am proud to announce that I will be bringing it to the world later this year to challenge you to empower yourself and accomplish greater things in life. To learn more, join my Discord at http://impacttheory.com/discordBig goals require DISCIPLINE. By it's very nature, discipline requires you to do hard things - and that is a skill you can LEARN. I'm teaching my process to build Ironclad Discipline in a new workshop - you can register at discipline.impacttheory.com!The fountain of youth is a mythical spring that has been the basis of many Hollywood movies and cosmetic marketing campaigns! Our obsession with youth and being young forever has been the source of cosmetic surgery and endless stories of ‘back in my day'.David Sinclair is a Professor in the Department of Genetics and co-Director of the Paul F. Glenn Center for Biology of Aging at Harvard Medical School. As a professor, scientific investigator and co-founder of multiple biotech companies, his knowledge with epigenetics and reverse aging is highly regarded among professional colleagues in the industry. He's appeared on dozens of podcasts, written books, and hosts his own podcast, Lifespan. As a guest on Health Theory the conversations around reverse aging and biological clocks are more than enlightening.Finding the root cause to aging and understanding how diet, exercise, and lifestyle choices impact our aging process puts the power of perspective and knowledge within your control. You don't have to guess or hope for a mythical spring of magical water that holds the secret of youth. You can make a decision everyday to turn back the clock, slow the aging process, and reset your age.SHOW NOTES:0:00 | Introduction to David Sinclair0:12 | Daily Hacks to Slow Aging28:50 | How to Reset Your Age58:43 | This Causes Aging1:32:23 | How to Understand AgingQUOTES:“80% of your longevity and health in old age is controllable and only 20% is dictated by your genes, the genome. The rest is your epigenome that responds to how we live [7:36]“Our livers are much smarter than our eyes and our mouths…” [24:35]“Anything that stresses your body, puts it into a state of shock is good in the long run.” [38:16]“When I boiled it down to its essence I realized aging was a loss of information.” [1:01:58]“That's part of the problem with aging, which is genes getting turned on when they should be kept off for decades, and then cells start to get confused.” [1:14:17]Follow David Sinclair: Website: https://sinclair.hms.harvard.edu/ YouTube: https://www.youtube.com/davidsinclairpodcast Podcast: https://anchor.fm/lifespan Instagram: https://www.instagram.com/davidsinclairphd/ Twitter: https://twitter.com/davidasinclair Facebook: https://www.facebook.com/davidsinclairphd

Ways to reach out to Dr. Pughhttps://sarapughleeds.co.uk/https://www.facebook.com/busysuperhumanhttps://twitter.com/spugh01Sara's BackgroundBachelor's in biochemistry and geneticsMaster in bioinformaticsPhD in molecular mechanisms10 years lab experienceHer Niche is on optimizing the environmental impact on our DNAAn Epigenome is like lights… we determine which ones turn on / expressLifestyle, diet,DNA is the music, Epigenome is the piano playerGene Expression control exaplesMTOR is switched on when eating, turned off when fastingWe need both in order to optimize autophagyThe process of detox is 4 phasesThe idea is to get toxins out of your cells then out of your bodyTake ALA, wait half an hourTake the binders - Benzonite Clay, Charcoal, Zeolite or ChlorellaFor Metals - ortho Solicic Acidhttps://www.amazon.com/dp/B00LPJLW8E?ref_=cm_sw_r_cp_ud_dp_CV4YH7J87HQ2QE3ZWSDWBlood test panel if 16 metals with ratiosQuicksilver metals panelhttps://www.quicksilverscientific.com/mercury-tri-test/Sara's Approach to diagnosing nutritionally impacted emotional and wellbeing disordersMeasure and address blood sugarE.g. Remove processed foodsLook for foods that ‘may' cause inflammationE.g. Gluten sensitivityLeaky Gut testingMay be triggered from alcoholWomen over 40 are more sensitive to histaminesGenerally takes 3 weeks to see resultsBDNF -  brain-derived neurotropic factor, a known antidepressant, and that's why a ketogenic diets or fasting, or just beginning to exercise more can help people on their mental health.Why a 72 hour fast is a big win for your healthBlood sugar spikes impact emotionsWearing a continuous glucose monitor can help you find both stressful impacts and find foods that you may not suspect are impacting your blood sugar.Dr. Pugh found out that dark chocolate impacted her blood sugarGetting your blood sugar back under control can take 48 hoursThere are 7 names for sugar in foodsFood companies leverage the ‘magic ratio' to make snacks addictiveThe fructose interferes with the leptin receptor in the brain, which is linked to satiety. That's why, you know, once you start a packet of cookies, it's really hard to stopSugar is often our first addiction in life.  Dr Pugh's focuses on movement, mobility and muscle balance Social cohesion is an important aspect of total healthShe recommends a ‘mix' of age groups and abilitiesCoaching with Empathy vs SympathyIncorporating resilience into manageable dosesCold ShowersCold boost metabolism, your immune system and helps with depress

In this episode of the Epigenetics Podcast, we caught up with Eleni Tomazou from St. Anna Children's Cancer Research Institute in Vienna to talk about her work on Epigenome-based precision medicine. The Tomazou lab studies Ewing sarcoma and the effects of Epigenetic factors on this disease. Ewing sarcoma is a type of cancer that affects bone and soft tissue of children and young adults, with a peak incidence at the age of 15. Ewing sarcoma is among the pediatric cancer types with the lowest survival rates and the development of novel therapies was obstructed by the limited understanding of the mechanisms behind the disease. Work done in Eleni Tomazou's group identified an epigenetic signature of Ewing sarcoma which, ultimately, lead to the possibility to diagnose Ewing sarcoma from liquid biopsies. The team is now looking to find actionable targets like enhancers to develop therapies, finding biomarkers to enable disease monitoring, and to further characterize these tumors to decipher intra-tumor epigenetic heterogeneity and characterize the developmental stage of the cell of origin.   References Tomazou, E. M., Sheffield, N. C., Schmidl, C., Schuster, M., Schönegger, A., Datlinger, P., Kubicek, S., Bock, C., & Kovar, H. (2015). Epigenome Mapping Reveals Distinct Modes of Gene Regulation and Widespread Enhancer Reprogramming by the Oncogenic Fusion Protein EWS-FLI1. Cell Reports, 10(7), 1082–1095. https://doi.org/10.1016/j.celrep.2015.01.042 Sheffield, N. C., Pierron, G., Klughammer, J., Datlinger, P., Schönegger, A., Schuster, M., Hadler, J., Surdez, D., Guillemot, D., Lapouble, E., Freneaux, P., Champigneulle, J., Bouvier, R., Walder, D., Ambros, I. M., Hutter, C., Sorz, E., Amaral, A. T., de Álava, E., … Tomazou, E. M. (2017). DNA methylation heterogeneity defines a disease spectrum in Ewing sarcoma. Nature Medicine, 23(3), 386–395. https://doi.org/10.1038/nm.4273 Terlecki-Zaniewicz, S., Humer, T., Eder, T., Schmoellerl, J., Heyes, E., Manhart, G., Kuchynka, N., Parapatics, K., Liberante, F. G., Müller, A. C., Tomazou, E. M., & Grebien, F. (2021). Biomolecular condensation of NUP98 fusion proteins drives leukemogenic gene expression. Nature Structural & Molecular Biology, 28(2), 190–201. https://doi.org/10.1038/s41594-020-00550-w Peneder, P., Stütz, A. M., Surdez, D., Krumbholz, M., Semper, S., Chicard, M., Sheffield, N. C., Pierron, G., Lapouble, E., Tötzl, M., Ergüner, B., Barreca, D., Rendeiro, A. F., Agaimy, A., Boztug, H., Engstler, G., Dworzak, M., Bernkopf, M., Taschner-Mandl, S., … Tomazou, E. M. (2021). Multimodal analysis of cell-free DNA whole-genome sequencing for pediatric cancers with low mutational burden. Nature Communications, 12(1), 3230. https://doi.org/10.1038/s41467-021-23445-w   Related Episodes Epigenomics (Henk Stunnenberg) Targeting COMPASS to Cure Childhood Leukemia (Ali Shilatifard) Cancer and Epigenetics (David Jones)   Contact Active Motif on Twitter Epigenetics Podcast on Twitter Active Motif on LinkedIn Active Motif on Facebook Email: podcast@activemotif.com

In this episode of the Epigenetics Podcast, we caught up with Manel Esteller, Director of the Josep Carreras Leukemia Research Institute to talk about his work on Epigenetics and Epitranscriptomics in Cancer. The focus of Manel Esteller's research career and the focus of his current team is to characterize the epigenome and epitranscriptome of cancer cells in comparison to healthy cells, and their interplay. Ultimately, their goal is to use this knowledge to develop new therapies for cancer. Key achievements from the Esteller lab began with the discovery of the first miRNA that undergoes specific cancer-methylation associated silencing. The team further identified many more miRNAs that also play a role in cancer. Next to miRNAs, Manel Esteller studied the influence of lncRNAs, enhancers and DNA methylation on cancer development and progression, insights that may be used to develop cancer biomarkers and potential treatments.     References Guil, S., Soler, M., Portela, A., Carrère, J., Fonalleras, E., Gómez, A., Villanueva, A., & Esteller, M. (2012). Intronic RNAs mediate EZH2 regulation of epigenetic targets. Nature Structural & Molecular Biology, 19(7), 664–670. https://doi.org/10.1038/nsmb.2315 Vizoso, M., Ferreira, H. J., Lopez-Serra, P., Carmona, F. J., Martínez-Cardús, A., Girotti, M. R., Villanueva, A., Guil, S., Moutinho, C., Liz, J., Portela, A., Heyn, H., Moran, S., Vidal, A., Martinez-Iniesta, M., Manzano, J. L., Fernandez-Figueras, M. T., Elez, E., Muñoz-Couselo, E., … Esteller, M. (2015). Epigenetic activation of a cryptic TBC1D16 transcript enhances melanoma progression by targeting EGFR. Nature Medicine, 21(7), 741–750. https://doi.org/10.1038/nm.3863 Agrelo, R., Cheng, W.-H., Setien, F., Ropero, S., Espada, J., Fraga, M. F., Herranz, M., Paz, M. F., Sanchez-Cespedes, M., Artiga, M. J., Guerrero, D., Castells, A., von Kobbe, C., Bohr, V. A., & Esteller, M. (2006). Epigenetic inactivation of the premature aging Werner syndrome gene in human cancer. Proceedings of the National Academy of Sciences of the United States of America, 103(23), 8822–8827. https://doi.org/10.1073/pnas.0600645103 Lopez-Serra, P., Marcilla, M., Villanueva, A., Ramos-Fernandez, A., Palau, A., Leal, L., Wahi, J. E., Setien-Baranda, F., Szczesna, K., Moutinho, C., Martinez-Cardus, A., Heyn, H., Sandoval, J., Puertas, S., Vidal, A., Sanjuan, X., Martinez-Balibrea, E., Viñals, F., Perales, J. C., … Esteller, M. (2014). A DERL3-associated defect in the degradation of SLC2A1 mediates the Warburg effect. Nature Communications, 5, 3608. https://doi.org/10.1038/ncomms4608 Rosselló-Tortella, M., Llinàs-Arias, P., Sakaguchi, Y., Miyauchi, K., Davalos, V., Setien, F., Calleja-Cervantes, M. E., Piñeyro, D., Martínez-Gómez, J., Guil, S., Joshi, R., Villanueva, A., Suzuki, T., & Esteller, M. (2020). Epigenetic loss of the transfer RNA-modifying enzyme TYW2 induces ribosome frameshifts in colon cancer. Proceedings of the National Academy of Sciences of the United States of America, 117(34), 20785–20793. https://doi.org/10.1073/pnas.2003358117 Castro de Moura, M., Davalos, V., Planas-Serra, L., Alvarez-Errico, D., Arribas, C., Ruiz, M., Aguilera-Albesa, S., Troya, J., Valencia-Ramos, J., Vélez-Santamaria, V., Rodríguez-Palmero, A., Villar-Garcia, J., Horcajada, J. P., Albu, S., Casasnovas, C., Rull, A., Reverte, L., Dietl, B., Dalmau, D., … Esteller, M. (2021). Epigenome-wide association study of COVID-19 severity with respiratory failure. EBioMedicine, 66, 103339. https://doi.org/10.1016/j.ebiom.2021.103339   Related Episodes CpG Islands, DNA Methylation, and Disease (Sir Adrian Bird) Targeting COMPASS to Cure Childhood Leukemia (Ali Shilatifard) Cancer and Epigenetics (David Jones)   Contact Active Motif on Twitter Epigenetics Podcast on Twitter Active Motif on LinkedIn Active Motif on Facebook Email: podcast@activemotif.com

Have you thought about reversing your "age" and being healthy again? Or thought about being able to live longer so that you could spend more quality time with your loved ones? In this episode, I was joined by Tony Robbins, an American author, speaker, and philanthropist, and Peter Diamandis, a Greek-American engineer, physician, entrepreneur, and author to talk about their new book,  Life Force: How New Breakthroughs in Precision Medicine Can Transform the Quality of Your Life & Those You Love!We also talked about how in the future, we could find a cure or a way to prevent Alzheimer's, save more life using gene editing, and potentially find a breakthrough medicine that could cure some uncurable disease!My new book Skip The Line is out! Make sure you get a copy wherever you get your new book!Join You Should Run For President 2.0 Facebook Group, and we discuss why should run for president.I write about all my podcasts! Check out the full post and learn what I learned at jamesaltucher.com/podcast.Thanks so much for listening! If you like this episode, please subscribe to “The James Altucher Show” and rate and review wherever you get your podcasts:Apple PodcastsStitcheriHeart RadioSpotify Follow me on Social Media:YouTubeTwitterFacebook

Check out our sponsors: ButcherBox: Sign up at ButcherBox.com/impact Athletic Greens: Go to athleticgreens.com/impact and receive a FREE 1 year supply of Vitamin D AND 5 free travel packs with your first purchase! Skillshare: Explore your creativity at skillshare.com/impacttheory for a 1 month FREE trial of Premium Membership. Ombre Lab: To get $30 off -- go to: tryombre.com/ImpactAre we closer to becoming biologically immortal? What would you strive to do or dream of if you could extend your life to even 150 years? Until recently the idea of longevity felt more like reaching your 90s and possibly 100 at best, and if you manage to accomplish that goal, a high quality of life would be best and expected. But what if you could extend your lifespan by even 10 years? Making sure that those years are exciting and meaningful would be a priority. Dr.David Sinclair, world renowned geneticist, is joining Tom in this episode to break down exactly why it is that we age on a cellular level, and what is now becoming possible in terms of slowing down our biological clock and even possibly reversing our biological age. If you want to know what you can do to start improving the quality of your aging life and stay younger longer this episode is for you, and you'll want to check out Dr. David Sinclair's newest podcast, Lifespan (link below).SHOW NOTES:0:00 | Introduction to David Sinclair0:28 | Why We Age9:40 | What Goes Wrong With Aging23:44 How to Reverse Aging37:35 | Face Adversity45:37 | How Metformin Works55:02 | Lifestyle for Longevity“We could have reversed aging just by making all cells a stem cell, we have the technology to do that.” [23:43]“So we're reversing the aging of the eye, that's not hard at all, but we can reverse the age of the liver, the skin, other labs are doing the spleen, thymus, through this method.” [31:13]“Humanity lucked out that we can actually do this and that there's a backup copy of youth in each of our cells that can be tapped into.” [32:03]“We don't think about what it's like at the end, it is not fun. It's not typically like, Oh, you just go to sleep. Those are the lucky ones.” [36:39]“The main concept that I think we all need to remember is that our bodies respond well to perceived adversity.” [38:55]Follow David Sinclair: Website: https://sinclair.hms.harvard.edu/ YouTube: https://www.youtube.com/davidsinclairpodcast Podcast: https://anchor.fm/lifespan Instagram: https://www.instagram.com/davidsinclairphd/ Twitter: https://twitter.com/davidasinclair Facebook: https://www.facebook.com/davidsinclairphd

In this episode of the Epigenetics Podcast, we caught up with Folami Ideraabdullah from the University of Chapel Hill to talk about her work on the environmental modulation of the epigenome during development. The lab of Folami Ideraabdullah focuses on studying how environmental factors modulate the epigenome. In particular the team investigates how Vitamin D levels influence epigenetic processes and, hence, the susceptibility for diseases like adipositas. Folami Ideraabdullah started with a genome-wide screen of DNA Methylation patterns that are observed after Vitamin D depletion. This work was then followed up by investigating the impact of Vitamin D depletion on mouse sperm DNA methylation.   References Xue, J., Schoenrock, S. A., Valdar, W., Tarantino, L. M., & Ideraabdullah, F. Y. (2016). Maternal vitamin D depletion alters DNA methylation at imprinted loci in multiple generations. Clinical Epigenetics, 8(1), 107. https://doi.org/10.1186/s13148-016-0276-4 Xue, J., Gharaibeh, R. Z., Pietryk, E. W., Brouwer, C., Tarantino, L. M., Valdar, W., & Ideraabdullah, F. Y. (2018). Impact of vitamin D depletion during development on mouse sperm DNA methylation. Epigenetics, 13(9), 959–974. https://doi.org/10.1080/15592294.2018.1526027 Xue, J., Hutchins, E. K., Elnagheeb, M., Li, Y., Valdar, W., McRitchie, S., Sumner, S., & Ideraabdullah, F. Y. (2020). Maternal Liver Metabolic Response to Chronic Vitamin D Deficiency Is Determined by Mouse Strain Genetic Background. Current Developments in Nutrition, 4(8), nzaa106. https://doi.org/10.1093/cdn/nzaa106   Related Episodes Nutriepigenetics: The Effects of Diet on Behavior (Monica Dus) Epigenetic Influence on Memory Formation and Inheritance (Isabelle Mansuy) Epigenetic Origins Of Heterogeneity And Disease (Andrew Pospisilik)   Contact Active Motif on Twitter Epigenetics Podcast on Twitter Active Motif on LinkedIn Active Motif on Facebook Email: podcast@activemotif.com

Check out our sponsors: ButcherBox: Sign up at ButcherBox.com/impact Athletic Greens: Go to athleticgreens.com/impact and receive a FREE 1 year supply of Vitamin D AND 5 free travel packs with your first purchase! Skillshare: Explore your creativity at skillshare.com/impacttheory for a 1 month FREE trial of Premium Membership. Ombre Lab: To get $30 off -- go to: tryombre.com/ImpactAre we closer to becoming biologically immortal? What would you strive to do or dream of if you could extend your life to even 150 years? Until recently the idea of longevity felt more like reaching your 90s and possibly 100 at best, and if you manage to accomplish that goal, a high quality of life would be best and expected. But what if you could extend your lifespan by even 10 years? Making sure that those years are exciting and meaningful would be a priority. Dr.David Sinclair, world renowned geneticist, is joining Tom in this episode to break down exactly why it is that we age on a cellular level, and what is now becoming possible in terms of slowing down our biological clock and even possibly reversing our biological age. If you want to know what you can do to start improving the quality of your aging life and stay younger longer this episode is for you, and you'll want to check out Dr. David Sinclair's newest podcast, Lifespan (link below).SHOW NOTES:0:00 | Introduction to David Sinclair0:28 | Why We Age9:40 | What Goes Wrong With Aging23:44 How to Reverse Aging37:35 | Face Adversity45:37 | How Metformin Works55:02 | Lifestyle for Longevity“We could have reversed aging just by making all cells a stem cell, we have the technology to do that.” [23:43]“So we're reversing the aging of the eye, that's not hard at all, but we can reverse the age of the liver, the skin, other labs are doing the spleen, thymus, through this method.” [31:13]“Humanity lucked out that we can actually do this and that there's a backup copy of youth in each of our cells that can be tapped into.” [32:03]“We don't think about what it's like at the end, it is not fun. It's not typically like, Oh, you just go to sleep. Those are the lucky ones.” [36:39]“The main concept that I think we all need to remember is that our bodies respond well to perceived adversity.” [38:55]Follow David Sinclair: Website: https://sinclair.hms.harvard.edu/ YouTube: https://www.youtube.com/davidsinclairpodcast Podcast: https://anchor.fm/lifespan Instagram: https://www.instagram.com/davidsinclairphd/ Twitter: https://twitter.com/davidasinclair Facebook: https://www.facebook.com/davidsinclairphd

In Episode 3 of the Lifespan Podcast, Dr. David Sinclair and Matthew LaPlante dive deeply into the science of non-dietary interventions that mimic adversity and promote health. They begin by highlighting how different types of physical activity (i.e., low-intensity aerobic exercise, high-intensity aerobic exercise, and weight training) protect against age-related disease and enhance longevity. David and Matthew additionally highlight the latest evidence behind hyperbaric oxygen therapy, cold therapy, and heat therapy. As they discuss different adversity mimetics, they also explain how these interventions influence aging at the molecular and physiological levels. Thank you to our sponsors: Athletic Greens - https://athleticgreens.com/sinclair Levels - https://levels.link/sinclair InsideTracker - https://insidetracker.com/sinclair Our Patreon page: https://www.patreon.com/davidsinclair Timestamps: (00:00:00) Introducing Episode 3: Exercise Hot Cold (00:01:01) A Pernicisous Element Called Iron (00:02:46) A Quick Primer on Free Radicals (00:05:42) Review of Dietary Takeaways (00:07:01) Sponsors (00:09:32 Biological Adversity & the Survival Circuit (00:13:24) Survival Sensors (i.e., mTOR, AMPK, and Sirtuins) & Communicators (e.g., Insulin) (00:17:25) Get Off Your Butt (00:19:40) Exercise Protects against Disease & Mortality (00:21:17) Daily Step Count and Walking After Eating (00:22:33) Exercise Activates AMPK and Creates More Mitochondria (00:24:03) Vigorous Exercise, Hypoxia, the Electron Transport Chain (00:28:19) Exercise Increases Glucose Sensitivity and Stimulates Blood Vessel Formation (00:32:13) The Epigenome and Biological Age are Impacted by Exercise (00:36:43) How to Measure your Biological Age (00:37:31) Exercise Recommendations (00:39:28) Wearables and Individualized Health Tracking (00:43:14) The Importance of Weight Training (00:46:08) Physical Activity & Senescent Cells (00:48:01) Wrap-up & Takeaways (00:49:47) Hyperbaric Oxygen Therapy (00:57:24) Cold Therapy (01:03:50) Applying Heat (01:07:04) Adversity Mimetics Produce Endorphins (01:08:07) A Basic Protocol for Mimicking Adversity (01:10:04) Next Week: Molecules & Supplements (01:10:45) Subscription & Support For the full show notes, including the peer-reviewed studies, visit the Lifespan podcast website. Please note that Lifespan with Dr. David Sinclair is distinct from Dr. Sinclair's teaching and research roles at Harvard Medical School. The information provided in this show is not medical advice, nor should it be taken or applied as a replacement for medical advice. The Lifespan with Dr. David Sinclair podcast, its employees, guests and affiliates assume no liability for the application of the information discussed. Title Card Photo Credit: Mike Blabac Special thanks to our research assistants, Adiv Johnson & Sarah Ryan.

In this episode, I am joined by Dr. David Sinclair, tenured Professor of Genetics at Harvard Medical School and an expert researcher in the field of longevity. Dr. Sinclair is also the author of the book Lifespan: Why We Age & Why We Don't Have To, and the host of the Lifespan Podcast, which launches January 5, 2022.  In this interview, we discuss the cellular and molecular mechanisms of aging and what we all can do to slow or reverse the aging process. We discuss fasting and supplementation with resveratrol, NAD, metformin, and NMN. We also discuss the use of caffeine, exercise, cold exposure, and why excessive iron load is bad for us. We discuss food choices for offsetting aging and promoting autophagy (clearance of dead cells). And we discuss the key blood markers everyone should monitor to determine your biological versus chronological age. We also discuss the future of longevity research and technology. This episode includes lots of basic science and specific, actionable protocols, right down to the details of what to do and when. By the end, you will have in-depth knowledge of the biology of aging and how to offset it.   Thank you to our sponsors: ROKA - https://www.roka.com - code "huberman" InsideTracker - https://www.insidetracker.com/huberman Magic Spoon - https://www.magicspoon.com/huberman   Dr. David Sinclair Links: Lifespan Podcast: https://lifespanpodcast.com  Twitter: https://twitter.com/davidasinclair Instagram: https://www.instagram.com/davidsinclairphd/   YouTube: https://www.youtube.com/davidsinclairpodcast   Lifespan (book): https://amzn.to/3mAZQjF  Aging Test Waitlist: https://www.doctorsinclair.com   Harvard Lab Website: https://sinclair.hms.harvard.edu    Our Patreon page: https://www.patreon.com/andrewhuberman    Supplements from Thorne: http://www.thorne.com/u/huberman    Social: Instagram - https://www.instagram.com/hubermanlab  Twitter - https://twitter.com/hubermanlab  Facebook - https://www.facebook.com/hubermanlab  Website - https://hubermanlab.com  Newsletter - https://hubermanlab.com/neural-network    Timestamps: 00:00:00 Dr. David Sinclair, Harvard Medical School 00:03:30 ROKA, InsideTracker, Magic Spoon 00:07:45 “Aging as a Disease” vs. Longevity & Anti-Aging 00:10:23 What Causes Aging? The Epigenome 00:15:53 Cosmetic Aging  00:17:15 Development Never Stops, Horvath Clock 00:20:12 Puberty Rate as a Determinant of Aging Rate 00:23:00 Fasting, Hunger & Food Choices 00:32:44 Fasting Schedules, Long Fasts, (Macro)Autophagy 00:34:50 Caffeine, Electrolytes  00:35:56 Blood Glucose & the Sirtuins; mTOR 00:37:55 Amino Acids: Leucine, “Pulsing” 00:44:35 Metformin, Berberine 00:50:29 Resveratrol, Wine 00:53:20 What Breaks a Fast? 00:56:45 Resveratrol, NAD, NMN, NR; Dosage, Timing 01:09:10 Are Artificial Sweeteners Bad for Us? 01:12:04 Iron Load & Aging 01:15:05 Blood Work Analysis 01:19:37 C-Reactive Protein, Cholesterol: Serum & Dietary 01:26:02 Amino Acids, Plants, Antioxidants 01:33:45 Behaviors That Extend Lifespan, Testosterone, Estrogen 01:40:35 Neuroplasticity & Neural Repair 01:46:19 Ice Baths, Cold Showers, “Metabolic Winter” 01:48:07 Obesity & How It Accelerates Aging, GnRH  01:52:10 Methylation, Methylene Blue, Cigarettes  01:56:17 X-Rays   01:59:00 Public Science Education, Personal Health 02:05:40 The Sinclair Test You Can Take: www.doctorsinclair.com 02:08:13 Zero-Cost Support & Resources, Sponsors, Patreon, Supplements, Instagram    Please note that The Huberman Lab Podcast is distinct from Dr. Huberman's teaching and research roles at Stanford University School of Medicine. The information provided in this show is not medical advice, nor should it be taken or applied as a replacement for medical advice. The Huberman Lab Podcast, its employees, guests and affiliates assume no liability for the application of the information discussed.   Title Card Photo Credit: Mike Blabac - https://www.blabacphoto.com 

We often associate illnesses and pains with old age. But our guest today reveals that the real cause of health problems is how you've lived your life. Accumulated amounts of stress can change our bodies down to the cellular level. Luckily, scientific discoveries such as peptide therapy can help our cells function better. Age is not the issue. If you take care of yourself, being older can mean being at the peak of your performance.  In this episode, Dr William Seeds joins us to discuss how our cells function and how epigenetic influences can harm our bodies. He shares how peptides and peptide therapy play a crucial role in keeping ourselves healthy and treating injuries and illnesses! As we age, our bodies slowly lose their ability to perform specific functions, including growth hormone production. But with the right intervention, including peptide therapy, a 100-year-old can produce just as many growth hormones as someone a quarter their age!  If you want to learn more about peptide therapy and how to age gracefully, then this episode is for you! Here are three reasons why you should listen to the full episode: Understand that taking care of our cells and helping them function properly is essential to living a healthier life.  Discover why diseases are not a function of age but how we have experienced life and accumulated negative influences on our cells.   Learn the importance of growth hormones and how peptides and peptide therapy can help with the neuroplasticity of our brains.  Resources Gain exclusive access and bonuses to Pushing the Limits Podcast by becoming a patron!  Peptide Protocols: Volume One by William Seeds  Life Extension: A Practical Scientific Approach by Durk Pearson and Sandy Shaw Pearson Chemistry by Drew Chan, Richard Hecker, Bob Hogendoorn, Kathryn Hiller, Louise Lennard, Mick Moylan, Pat O'Shea, Maria Porter, Patrick Sanders, Paul Waldron, Jim Sturgiss   Boulder Longevity Institute  Want to learn more from Dr William Seeds? Listen to his podcast, Sex, Drugs, and Epigenome. Connect with Dr William Seeds: Website | Youtube | LinkedIn | Instagram | Twitter     Get Customised Guidance for Your Genetic Make-Up For our epigenetics health programme, all about optimising your fitness, lifestyle, nutrition and mind performance to your particular genes, go to  https://www.lisatamati.com/page/epigenetics-and-health-coaching/. Customised Online Coaching for Runners CUSTOMISED RUN COACHING PLANS — How to Run Faster, Be Stronger, Run Longer  Without Burnout & Injuries Have you struggled to fit in training in your busy life? Maybe you don't know where to start, or perhaps you have done a few races but keep having motivation or injury troubles? Do you want to beat last year's time or finish at the front of the pack? Want to run your first 5-km or run a 100-miler? ​​Do you want a holistic programme that is personalised & customised to your ability, goals, and lifestyle?  Go to www.runninghotcoaching.com for our online run training coaching. Health Optimisation and Life Coaching Are you struggling with a health issue and need people who look outside the square and are connected to some of the greatest science and health minds in the world? Then reach out to us at support@lisatamati.com, we can jump on a call to see if we are a good fit for you. If you have a big challenge ahead, are dealing with adversity or want to take your performance to the next level and want to learn how to increase your mental toughness, emotional resilience, foundational health, and more, contact us at support@lisatamati.com. Order My Books My latest book Relentless chronicles the inspiring journey about how my mother and I defied the odds after an aneurysm left my mum Isobel with massive brain damage at age 74. The medical professionals told me there was absolutely no hope of any quality of life again. Still, I used every mindset tool, years of research and incredible tenacity to prove them wrong and bring my mother back to full health within three years. Get your copy here: https://shop.lisatamati.com/collections/books/products/relentless. For my other two best-selling books Running Hot and Running to Extremes, chronicling my ultrarunning adventures and expeditions all around the world, go to https://shop.lisatamati.com/collections/books. Lisa's Anti-Ageing and Longevity Supplements  NMN: Nicotinamide Mononucleotide, an NAD+ precursor Feel Healthier and Younger* Researchers have found that Nicotinamide Adenine Dinucleotide or NAD+, a master regulator of metabolism and a molecule essential for the functionality of all human cells, is being dramatically decreased over time. What is NMN? NMN Bio offers a cutting edge Vitamin B3 derivative named NMN (beta Nicotinamide Mononucleotide) that can boost the levels of NAD+ in muscle tissue and liver. Take charge of your energy levels, focus, metabolism and overall health so you can live a happy, fulfilling life. Founded by scientists, NMN Bio offers supplements of the highest purity and rigorously tested by an independent, third-party lab. Start your cellular rejuvenation journey today. Support Your Healthy Ageing We offer powerful, third-party tested NAD+ boosting supplements so you can start your healthy ageing journey today. Shop now: https://nmnbio.nz/collections/all NMN (beta Nicotinamide Mononucleotide) 250mg | 30 capsules NMN (beta Nicotinamide Mononucleotide) 500mg | 30 capsules 6 Bottles | NMN (beta Nicotinamide Mononucleotide) 250mg | 30 Capsules 6 Bottles | NMN (beta Nicotinamide Mononucleotide) 500mg | 30 Capsules Quality You Can Trust — NMN Our premium range of anti-ageing nutraceuticals (supplements that combine Mother Nature with cutting edge science) combats the effects of aging while designed to boost NAD+ levels. Manufactured in an ISO9001 certified facility Boost Your NAD+ Levels — Healthy Ageing: Redefined Cellular Health Energy & Focus Bone Density Skin Elasticity DNA Repair Cardiovascular Health Brain Health  Metabolic Health My  ‘Fierce' Sports Jewellery Collection For my gorgeous and inspiring sports jewellery collection, 'Fierce', go to https://shop.lisatamati.com/collections/lisa-tamati-bespoke-jewellery-collection. Episode Highlights [05:29] William's Background and His Father's Death William used to train with his father when he was a young athlete.  Unfortunately, he lost his father on the track right before his eyes. He could not do anything to save him.  His life changed drastically afterwards. As the eldest sibling, he had to take charge.  William questioned how someone could seem like they're in the best of health but die so early. This thought led him to learn more about biochemistry and molecular biology.  In the full episode, he shares the one book that jump-started his interest in biology and chemistry.   [09:15] Shifting from Business to Medical School William shares that he was a business major, but he spent most of his college days researching and reading more about biochemistry.  He became so good that he started helping people with their biology classes.   When he graduated from business school, he knew that his path was in medicine. Along the way, he faced people telling him that he couldn't do it.  However, he found a way to enter medical school by taking accelerated classes during the summer. These classes let him qualify for the entrance exam.  People's advice, even disbelief, can help us achieve the impossible. Listen to the full episode to learn more about William's shift and how he even got early admission!   [16:59] The Value of Constant Learning When William went into medical school, there were many things that didn't make sense to him. So he used to argue and get in trouble.  He observed that the cell is more important than we give it credit for. While it's good to know its components, it's more important to understand how we can use it to treat illnesses.  His work on nutrition and the cell built his orthopedic career and research on peptides. Eventually, he taught others about the application of peptides in their practices.  Learning is not about being smart; it's about constantly working hard to gain and build knowledge.   You have the power to explore what interests you and build expert-level knowledge based on the research you can find online. [25:32] What Are Peptides?  Peptides are signalling agents that help maintain cellular health.  There are many different names of peptides, depending on how and where they are made. They can be called hormones, enzymes, or more.  Some of the most significant scientific discoveries started with the study of peptides. For example, insulin is one of the major peptides discovered back in the 1920s.  Peptides may seem complicated, but you can make people understand them.  William encourages everyone to learn more about it to make better decisions for their health, but it is the job of empowered people to educate people.  [34:20] Peptide Therapy and Epigenetics Our genetics are unchangeable, but epigenetic influences can change how our cells transcribe and translate our gene's instructions.  Epigenetic influences include things that affect us every day, like stress, aging, disease, and more.  The work that William does, including peptide therapy, is all about epigenetics.  Cells have their own intelligence. We just need to give them the ability to correct themselves.  For instance, we need to maintain cellular redox — the thermodynamics of the cell. [37:02] What Happens When a Cell is Not Performing Well When epigenetic influences harm the cells' performance, they become senescent cells.  Our bodies are programmed to kill these unhealthy cells, but this doesn't happen all the time.  Senescent cells are the key to aging and diseases.  When these cells establish themselves in the body, it is hard to get rid of them, especially since they can build up over time.    [41:48] Aging and Growth Hormones As we age, the brain loses the capacity to release the same amount of growth hormone, which is the master regulator of our body.  By the age of 30, we experience a slow decline in how much growth hormone we can produce, which decreases even more with age.  However, you will never lose the capacity to create growth hormones.  What dictates this production are the events in your life that affect your body and whether you have a buildup of senescent cells.  Peptides and peptide therapy can help you regain the ability to release endogenous growth hormones based on your body's demand.  [44:29] How to Increase Growth Hormones There are over 100 types of growth hormones. Each one is released based on the body's demand.   Cells can recognise if synthetic growth hormones do not match the demand, and this can be harmful.  One way we naturally release growth hormones is during sleep.  [48:22] The Value of Growth Hormones  Peptides can help not only with improving the increase of growth hormones but also with neuroplasticity.  Certain peptides have specific uses. For example, Ipamorelin allows the secretion of growth hormone within 20 minutes of usage. This is typically used before sleeping and upon waking.  Brain injuries tend to shut down more growth hormones. This goes to show how improving brain function involves many levels. Senescent cells suppress the stem cells' ability to perform repairs and can convert stem cells to senescent stem cells. Listen to the full episode to learn more about growth hormone pathways and how they improve function!  [53:07] Age is Not the Issue Even if neural pathways have been damaged, the brain can build new ones.  Age is not an issue; older people can still produce new neural pathways.  There are a lot of aspects needed to create these pathways. It involves timing, planning, building momentum, and supplements. The gut plays an important role in recovering from brain injuries since it makes a lot of neurotransmitters. You also need to look at the cell membrane because you can lose certain phospholipids vital to conduction in axons and how neurons work. [56:49] There is Hope William's goal is to help people have enough knowledge to know that they can prevent themselves from things like a traumatic brain injury.  Certain diseases take time to incubate, so you won't even know you're in its path until it's too late.  We must take advantage of the knowledge that we can improve our cell's functions: we can change a cell to be more protective, more efficient, and keep it that way.  We should aim to live our lives to the fullest capacity, no matter our age. William shares that even though he is already in his 60s, his capacity is at its peak.   7 Powerful Quotes [29:25] ‘If anybody tells you something is too complicated, you have to have a PhD to understand that, right away, you should call bullshit because it means [they] just can't teach well.' [29:48] 'We all have the same capability of understanding. So our job is to educate people of what they have out there and not to keep them thinking they can't learn this.'  [44:58] ‘The cell knows what to make when the body has the demand.' [50:21] ‘Growth hormone has some tremendous downstream effects that are effective in so many ways, in helping people regain the ability to improve cellular metabolism in the brain.' [57:32] ‘We can change a cell to be more protective, more efficient, and keep that cell.' [57:41] ‘We're not looking to live at 150 years of age… We're looking to live every day of our lives at our fullest capacity.' [58:13] ‘There is just so much that people deserve to know that they can be doing it, that they can change their lives no matter what state they're in.' About Dr William Seeds Dr William Seeds is a board-certified orthopedic surgeon. For over 25 years, he has been a leading physician specialising in all aspects of sports medicine and total joint treatments. Dr Seeds is also the world's leading authority on peptide therapy, with training in advanced metabolic and nutritional medicine.  In his constant pursuit of medical research, he has published several research papers. Among his works is the first handbook on peptides written for practitioners, Peptide Protocols Volume One. He is the founder and president of the Seeds Scientific Research and Performance (SSRP), the training institute on cellular medicine and peptide therapy for medical practitioners.   Dr Seeds is also the Chief of Surgery and Orthopedic Residency Site Director for University Hospital, Conneaut and Geneva, Ohio. He has also been honoured at the NFL Hall of Fame for his medical services as a Professional Medical Consultant for the MLB, NHL, NBA, and NBC's Dancing with the Stars.  Interested in Dr Seed's work? Check out his website. You can also reach him on Youtube, LinkedIn, Instagram, and Twitter.       Enjoyed This Podcast? If you did, be sure to subscribe and share it with your friends! Post a review and share it! If you enjoyed tuning in, then leave us a review. You can also share this with your family and friends so they can learn more about peptide therapy and how cells play a critical role in our lives. Have any questions? You can contact me through email (support@lisatamati.com) or find me on Facebook, Twitter, Instagram and YouTube. For more episode updates, visit my website. You may also tune in on Apple Podcasts. To pushing the limits, Lisa  

In this episode of the Personalized Medicine Podcast we are returning to the topic of aging. It is our pleasure to introduce to you the co-founder & CEO of Rejuvenate Bio, Daniel Oliver. Dan studied Mechanical Engineering & Business at Caltech and obtained an MBA from Harvard Business School. After completing his studies, Dan has co-founded several successful companies in very diverse industries. With Rejuvenate Bio Dan and his co-founder Noah Davidsohn are developing new gene therapies to address aging and age-related diseases.In our conversation with Dan we discussed: ◦ The founding story of Rejuvenate Bio ◦ Role of serendipity in founding successful start-ups ◦ George Church and his support in starting Rejuvenate Bio ◦ Gene therapy as a new way to reverse aging ◦ Epigenetic approach to aging ◦ Tackling aging in dogs ◦ Dan's view on the future of aging research ◦ Bias towards action as an important trait of successful startup foundersGet in touch with Dan: ◦ LinkedIn: https://www.linkedin.com/in/danielcoliver/ ◦ Twitter: @DanielCOliver ◦ Web: https://www.rejuvenatebio.com/Make sure to download the full show notes with our guest's bio, links to their most notable work, and our recommendations for further reads on the topic of the episode at pmedcast.com

With the stress and uncertainty encountered globally since March 2020, people are now starting to feeling the cumulative effects, resulting in exhaustion, anxiety, pain and burn out.Within this episode, Heidi delves into how we can still live in the moment, adopting Total Somatic principles to support our overall health & wellbeing.Learn how you can adopt Soma Intelligence, an important principle taught within the Total Somatics membership.TO OBTAIN YOUR FREE PDF WITH THE 10 WAYS TO RECONNECT & ENHANCE YOUR SOMA INTELLIGENCE, GO TO: https://bit.ly/3lBUp3ETO LEARN MORE:https://TotalSomatics.comFREE EBOOK:https://totalsomatics.com/free-ebook-somatics-what-is-it-how-can-it-help-me/TO JOIN THE TOTAL SOMATICS MEMBERSHIP WAIT LIST:https://totalsomatics.com/join-now/TO VISIT THE TOTAL SOMATICS ONLINE SHOP:https://totalsomatic.com/audio-instruction/Support the show (http://paypal.me/TotalSomatics)

ในร่างกายของเรามีระบบการอ่าน Code ด้วยนะมันคือ “ระบบพันธุศาสตร์ด้านกระบวนการ เหนือพันธุกรรม” เราเรียกสั้นๆว่า Epigenome มันทำหน้าที่ในการควบคุมกระบวนการทางเมตาบอลิสมทั้งหมดในร่างกาย ถ้าการอ่านข้อมูลนี้เกิดผิดพลาด นั่นก็หมายถึงการนำไปสู่ความแก่ชรา วันนี้พวกเราไปเจอหนังสือ Lifespan "แก่ช้า อายุยืน" โดย Prof.David Sinclair ได้นำเสนอทฤษฎีที่เป็น “Information Theory of Aging” โดยสรุปเป็น 5 วิธีชะลอวัยชราเข้าใจง่าย ถ้าพร้อมแล้วไปฟังกันเลย ชมสด : https://fb.watch/9kUoD4bSkq/ _______________________________ ช่องทางการฟัง Podcast ต่างๆ Apple Podcast https://apple.co/2yXeD2Q Sportify https://spoti.fi/3g0IBDJ Podbean https://soulriwit.podbean.com Google Podcast https://bit.ly/2X9PhH3 Youtube https://bit.ly/3fYk2ae Facebook https://facebook.com/soulriwit   #SoulRiwitPodcast #PodcastThailand #LifeSpan #ชะลอวัย

In this episode of my Hungry for More series, I talk about the science behind epigenetics, specifically focusing on how our choices, behavior, and environment affect the expression of the genes we have in our DNA. Many of us feel like a victim of our own genes, and here, I remind you that you are your own fate's pilot – that you are more than the genetics encrypted in your body! I also share with you studies and other evidence which prove that through wiser health choices, we can actually get to take care of ourselves and of those who surround us as well.Highlights:Chemical modifications that can be made in order to affect the usability of one's genes in the body;Parents' choices that affect their health also affect the offspring's even before birth;Our choices and behaviors not only impact our DNA, but also impact the health and well-being of those around us.Check out previous episodes in my Hungry for More series if you haven't already! They'll really help you understand hunger.It is a great way of understanding why people struggle with their weight every day due to the lack of desire to eat certain things they enjoy eating as well as other factors such as stress levels, which affect the production of ghrelin hormone (the "I'm hungry" hormone).  Here are our top recommended episodes.Episode 2: The Science Behind Emotional EatingEpisode 7: 10 Practical Tips for Weight LossEpisode 10: Hunger for Perfection: How Your Perfectionism is Undermining Your SuccessMy new book Hungry for More: Stories and Science to Inspire Weight Loss From The Inside Out is now available! If you'd like a hardcover, personalized, autographed copy with free shipping, use the code freeship at hungryformore.net.Check out the new 30-Day Journaling Mini-Course.Find more inspiration, join my newsletter, or see my curated collection of supplements and protein bars at dradrienneyoudim.com.Don't forget to follow Dehl Nutrition on Instagram and Facebook! 

Heidi Hadley interviews Rebekkah Finnigan on the Somatic Movement & Mindset Podcast.Rebekkah recently held a workshop for The Total Somatics Members at www.TotalSomatics.com.  She highlighted the pillars for great health and wellbeing, whilst delving into brain & gut health, with its role in the areas of inflammation and immunity.TO LEARN MORE ABOUT REBEKKAH FINNIGAN:WEBSITE: www.energyinmotioncoach.comSOCIAL: @energyinmotionEMAIL: rebekkah@energyinmotioncoach.com5 SIMPLE HEALTH TIPS TO RECLAIM YOUR ENERGY:https://mailchi.mp/energyinmotioncoach.com/reclaimyourenergyTO LEARN MORE ABOUT HEIDI HADLEY & TOTAL SOMATICS:www.TotalSomatics.comwww.HeidiHadley.comINSTAGRAM: @total.somaticsFACEBOOK: @TotalSomaticsFREE EBOOK: https://totalsomatics.com/free-ebook-somatics-what-is-it-how-can-it-help-me/BECOME A TOTAL SOMATICS MEMBER: https://totalsomatics.com/join-now/TOTAL SOMATICS ONLINE SHOP: https://totalsomatics.com/audio-instruction/Support the show (http://paypal.me/TotalSomatics)

Recorded June 13, 2021Current Episodes athttps://walkinverse.buzzsprout.com/I am moving all podcast here slowly. I will keep buzzsprout for all public reports and here for member only content.Report #42, "Meet Moderna: Taxpayer Funded, DARPA Approved."In this report we will look at the origin of Moderna and their connection to the Military's advanced research program funded by American taxpayers. Grab a pen and notebook and enjoy the report.* e-book report, “Meet Moderna.”Paid subscribers can download any report or e-book from the library, and gain access to all premium content. Also join me on telegram for other interesting updates. Every subscription allows me to continue fight in sharing the truth and helps me support my family. Thank you.WIV Reports — Uncensored is a reader-supported publication. To receive new posts and support my work, consider becoming a free or paid subscriber.ReferencesRaul Diego. 2020. “A DARPA-Funded Implantable Biochip to Detect COVID-19 Could Hit Markets by 2021.” MintPress News (blog). September 17, 2020.Speights, Keith. 2020. “How Much Money Will Moderna Make From Its COVID Vaccine?” The Motley Fool. December 10, 2020.Robert Langreth and Naomi Kresge. 2020. “Moderna Wants to Transform the Body Into Vaccine-Making Machine.” Bloomberg.Com, August 11, 2020.WSKG. 2021. “CRISPR Scientist's Biography Explores Ethics Of Rewriting The Code Of Life.” WSKGWSKG. March 8, 2021.Max McNabb. 2021. “Doctor Testifies on COVID Vaccine Dangers to Texas Senate Committee.” Authentic Texan (blog). May 14, 2021.Angus Liu. 2021. “Moderna Lures Novartis' Top Lawyer to Be Its Own as COVID-19 Vaccine Rollout Raises Legal Risks.” FiercePharma. March 8, 2021.Ramola D. 2021. “BREAKING: Moderna COVID Vaccine Found to Contain a DEADLY POISON ‘SM-102 – Not for Human or Veterinary Use, Acutely Toxic, Fatal in Contact with Skin, Carcinogenic, Causes Infertility, Causes Nerve, Liver, Kidney Damage.'” The EveryDay Concerned Citizen. May 18, 2021.Kira Peikoff. 2018. “3 Futuristic Biotech Programs the U.S. Government Is Funding Right Now.” Leaps. October 31, 2018.Franz Walker. 2020. “DARPA Funded Implantable Biochip Can Potentially Be Used to Deploy Moderna's MRNA Vaccine.” Nanotechnology News. October 12, 2020.Patrick Tucker. 2020. “A Military-Funded Biosensor Could Be the Future of Pandemic Detection.” Defense One. March 3, 2020.Dr. Eric Van Gieson. n.d. “Epigenetic Characterization and Observation.” DARPA. Accessed April 28, 2021.DHS. 2018. “WMD Detection, Epigenome, DARPA.” Homeland Security News Wire. February 9, 2018.WATCH, JUDICIAL. 2019. “Census Bureau Still Hiring Felons, Child Sex Offenders Pass Background Check.” Legal. Judicial Watch. December 17, 2019.Ken Kingery. 2019. “Identifying the Epigenetic Fingerprints of Weapons of Mass Destruction.” Duke Pratt School of Engineering. September 12, 2019. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit walkinverse.substack.com/subscribe

#therichsolution #epigenetics #empoweredhealthJoin Gwen Rich for another episode on mojo50.com @ 10:00am CT. As your health advocate she will speak on the topic of "Epigenetics: Can Your Decisions Affect Your Health, Your Families & Generations To Come?”. Epigenetics is an emerging field of science that, eventually, could have massive implications on how we address our health and that of future generations. Listen at 10:00am CT on:www.mojo50.comiHeart RadioiTunesAppleLive streaming via: YouTube and Facebook:https://www.facebook.com/Therichsolution/https://www.youtube.com/c/therichsolution

Roundtable discussion involving Dr. Yunsung Lee, Dr. Anil P.S. Ori, Dr. Ake T. Lu, and Dr. Steve Horvath talking about the connections between Dr. Horvath's two papers submitted to the Journal Aging-US “Epigenome-wide association study of leukocyte telomere length” and “DNA methylation-based estimator of telomere length” "Epigenome-wide association study of leukocyte telomere length" Full text - https://www.aging-us.com/article/102230/text Press release - https://www.aging-us.com/news_room/epigenome-wide-association-study-of-leukocyte-telomere-length "DNA methylation-based estimator of telomere length" - Full text - https://www.aging-us.com/article/102173/text Press release - https://www.aging-us.com/news_room/dna-methylation-based-estimator-of-telomere-length