Podcasts about Telomerase

If you want to get leaner and live longer check out https://milliondollarbodylabs.com   Why do our bodies slowly break down, even if we eat right and exercise? We dive deep into the biological switch at the cellular level that determines human longevity.   I spoke with Dr. Bill Andrews, the father of telomere biology and a co-discoverer of telomerase. He explained why aging happens: telomeres, the protective caps on our DNA, shorten every time a cell divides, acting like a cellular clock. We talked about an obsession with curing aging. We discussed methods to re-lengthen telomeres, primarily using plant extracts to turn the telomerase gene back on in normal cells, a process currently being researched by his company, Sierra Sciences. We also discussed the biggest myth in anti-aging science and how certain types of exercise can accelerate aging by increasing cell division.   Key Takeaways Telomeres are DNA sequences found at the tips of chromosomes; they function as protective caps (like shoelace aglets) and control gene expression. The shortening of telomeres occurs every time a cell divides because the cell lacks the ability to duplicate the entire DNA strand to the very end (analogous to a bricklayer falling off the end of a wall before placing the last brick). This phenomenon represents a hard, fast limitation on our lifespan. Telomerase is the enzyme responsible for preventing telomere shortening. Reproductive cells (primordial germ cells) possess this enzyme, which prevents the species from going extinct with ever-shorter telomeres. The primary mission of current research is to reactivate the telomerase gene in somatic cells (non-reproductive body cells), where the gene's "dimmer switch" is currently turned off. Sierra Sciences focuses 95% of its efforts on screening fractionated nutraceuticals (plant extracts), looking for small molecules that can bind to and dislodge the repressor protein that keeps the telomerase gene turned off. Dr. Andrews states that the biggest myth in longevity is the claim that a product reverses aging simply because it reverses a biomarker correlated with aging. He uses the "Betty White Test" to demonstrate that no product currently exists that truly reverses aging. Activities that force extensive cell division, such as muscle bodybuilding, microdermabrasion (using acids or lasers on the face), and immune boosters, accelerate telomere shortening and therefore accelerate aging. When pursuing endurance exercise (running, biking, kayaking), it should be done consistently and kept fun; too little or too much intensity accelerates aging (a "Goldilocks effect"). Resources Documentary: The Immortalist https://theimmortalists.com Company/Website: Touchstone Essentials https://thegoodinside.com Company/Website: Sierra Sciences https://sierrasci.com Contact: Bill Andrews' email BAndrews@SierraSci.com   Nate Palmer: The founder of The Million Dollar Body and author of "The Million Dollar Body Method", Nate has been coaching for over 15 years and has worked personally with over 1,000 clients. Website: https://milliondollarbodylabs.com/ Book: The Million Dollar Body Method Lean Energy Stack: https://milliondollarbodylabs.com/pages/lean Instagram: @_milliondollarbody

Can We Slow — or Reverse — Aging? Telomeres, Telomerase & LongevityClick On My Website Below To Schedule A Free 15 Min Zoom Call:www.Over40FitnessHacks.comOver 40 Fitness Hacks SKOOL Group!Get Your Whoop4.0 Here!Dr. Bill Andrews - Telomere Health & Longevitywww.thegoodinside.com - Touchstone Essentials supplements.Email: BAndrews@SierraSci.comGuest snapshot: Dr. Bill Andrews—biotech veteran and founder of Sierra Sciences—has spent his career chasing a practical way to slow (and ultimately reverse) human aging. Inspired by a childhood mission from his dad to “find a cure for aging,” he helped lead the discovery of human telomerase at Geron in the 1990s.Why we age: Aging isn't great for the individual, but it benefits the species (greater diversity and adaptability). Mechanistically, “wear and tear” accumulates—and our ability to replace damaged cells is capped by the Hayflick limit.Ride tickets analogy: Every time a cell divides it “uses a ticket.” Those tickets are telomeres (the DNA caps on chromosomes). When tickets run out, cells enter senescence and die.Telomerase: In reproductive cells, the enzyme telomerase adds tickets back, keeping telomeres long—why children aren't born “older” than their parents. In most other cells, the telomerase gene is repressed.His team screens plant extracts to dislodge repressor proteins on the telomerase gene “dimmer switch,” aiming to partially turn it back on.Partial activation ≠ reversal, but it can slow telomere shortening (slowing aging). He believes stronger activators that can win the “tug-of-war” and lengthen telomeres meaningfully could arrive in ~1–3 years if progress continues.Andrews licensed several top nutraceutical fractions that, in his assays, induce telomerase expression modestly and include antioxidants/anti-inflammatories to reduce accelerated shortening.Notable: a turmeric fraction without curcumin (their strongest inducer), plus pomegranate, skullcap root, “gal nut,” and others. No “proprietary blend” label—ingredients are listed individually.He stresses Telo-Vital slows aging; occasional anecdotal reversals (hair/vision/sleep) may occur when tissues have critically short telomeres that are easier to re-lengthen.Do something daily. Consistent, enjoyable endurance-style movement can lower inflammation/oxidative stress; stop before it stops being fun.What can accelerate shortening: frequent senolytics (create gaps → more cell division), high alcohol (liver turnover), growth-hormone/“immune boosters” that drive cell division, and chronic inflammation/oxidative stress.What helps slow acceleration: anti-inflammatory/antioxidant strategies, better glucose control (he mentions a product that “converts sugar to fiber”), mitochondrial support like urolithin A and NAD/Niagen (NR).Product: Telo-Vital (Touchstone Essentials) — site: thegoodinside.comDr. Andrews (science questions): BAndrews@SierraSci.comHe can share recommended YouTube talks on telomeres/telomerase and aging.Bottom line: Telomere shortening is a central, measurable driver of aging. Today's tools may slow that process; Andrews is racing to make meaningful lengthening practical next.If you're interested in online personal training or being a guest on my podcast, "Over 40 Fitness Hacks," you can reach me at brad@over40fitnesshacks.com or visit my website at:www.Over40FitnessHacks.comAdditionally, check out my Yelp reviews for my local business, Evolve Gym in Huntington Beach, at https://bit.ly/3GCKRzV

In this episode, Dr. Bill Andrews joins Dr. Buck Joffrey to discuss the critical role of telomeres and telomerase in aging and cellular health. He explains how telomeres shorten with each cell division, leading to aging and cellular senescence. Dr. Andrews emphasizes the importance of inducing telomerase to potentially reverse aging and shares insights from his research on telomerase inducers. He also addresses the challenges in longevity research, the relationship between telomeres and the hallmarks of aging, and the potential of gene therapy. The conversation concludes with a discussion on lifestyle factors that can influence aging and the future of aging research. Learn more about Dr. Bill Andrews: https://sierrasci.com/dr-bill-andrews/ - Download Dr. Buck Joffrey's FREE ebook, Living Longer for Busy People: https://ru01tne2.pages.infusionsoft.net/?affiliate=0 Book a FREE longevity coaching consultation with Dr. Buck Joffrey: https://coaching.longevityroadmap.com/

BUFFALO, NY — July 15, 2025 — A new #research paper was #published in Aging (Aging-US) Volume 17, Issue 6, on June 5, 2025, titled “Senescence caused by telomerase inactivation in myeloid, mesenchymal, and endothelial cells has distinct effects on cancer progression.” In this study, first author Joseph Rupert, along with corresponding author Mikhail G. Kolonin and colleagues from The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, McGovern Medical School, at The University of Texas Health Sciences Center at Houston, investigated how aging-related changes in different cell types affect cancer progression. By turning off telomerase in specific cell populations in mice, the researchers discovered that cell aging, or senescence, can slow primary tumor growth but also trigger unexpected effects. This work sheds light on the complex relationship between aging cells and cancer and may help guide future anti-cancer strategies. The team used genetically modified mice to deactivate telomerase, the enzyme that maintains chromosome ends, specifically in immune, connective tissue, and blood vessel cells. This caused these cells to enter a state of senescence, where they stop dividing and release inflammatory signals. The researchers then implanted breast, prostate, and pancreatic cancer cells into the mice and tracked how tumors developed. They found that when telomerase was inactivated in immune cells or connective tissue cells, tumors grew more slowly. However, these tumors showed signs of increased tissue damage and potential aggressiveness. Interestingly, when telomerase was turned off in endothelial cells, which cover blood vessels, tumors shrank and became poorly supplied with blood, leading to oxygen deprivation. In the case of pancreatic cancer cells, this low-oxygen environment made them more likely to spread to the liver, highlighting a potential risk of targeting these cells. “[…] this study shows that senescence and metabolic dysfunction resulting from telomerase inactivation in distinct cells in the tumor microenvironment have different effects on tumor growth and metastasizing of carcinomas.” This research provides important insights into how aging cells within the tumor microenvironment (TME) influence cancer behavior. While senescence in certain cell types can help suppress tumor growth, it may also create conditions that favor cancer metastasis. These findings highlight the need to consider cell type-specific effects when developing therapies that target senescent cells. By mapping how different cell populations contribute to cancer progression in aging tissues, this study opens the door for more precise approaches to prevent both tumor growth and spread. DOI - https://doi.org/10.18632/aging.206268 Corresponding author - Mikhail G. Kolonin - mikhail.g.kolonin@uth.tmc.edu Video short - https://www.youtube.com/watch?v=py8wFKj7enE Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206268 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, senescence, telomerase, myeloid, mesenchymal, endothelial To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

Today I'm speaking with Liz Parrish, the founder and CEO of BioViva, on the Longevity Optimization Podcast. In this episode, we explore groundbreaking advancements in gene therapy and its potential to cure age-related diseases. Liz shares her personal journey that led to the creation of BioViva, providing insights into the mechanisms of gene therapy and the current landscape of approved therapies. Our conversation delves into the hallmarks of aging, the role of specific genes like follistatin and telomerase, and the future of gene therapy as a preventative measure for health optimization.Liz Parrish is a pioneering figure in the field of gene therapy, dedicated to advancing the science of longevity and health optimization. Throughout our discussion, she addresses the ethical considerations surrounding gene editing and the implications for future generations. We also discuss the significance of gene therapy in combating aging, the role of telomeres in longevity, and the misconceptions about telomerase and cancer. Additionally, Liz explores the potential benefits of hyperbaric oxygen therapy and shares her personal experiences with gene therapy. The conversation touches on skincare, the philosophy of longevity, and the empowerment of women through advancements in gene therapy, highlighting the transformative potential of these innovations for future health.Let's be friends!Instagram: https://www.instagram.com/kaylabarnes/?hl=enTikTok: https://www.tiktok.com/@femalelongevityX: https://x.com/femalelongevityWebsite: https://kaylabarnes.comJoin Female Longevity Community: https://kayla-barnes-lentz.circle.so/checkout/become-a-member Follow Liz ParrishFollow Her on IG: https://www.instagram.com/lizlparrish/Timestamps00:00 Introduction to Gene Therapy and Longevity03:10 The Birth of BioViva and Personal Motivation06:05 Advancements in Gene Therapy and Regenerative Medicine08:49 Understanding Gene Therapy: Mechanisms and Applications11:56 Current Approved Gene Therapies and Their Impact15:08 Exploring the Hallmarks of Aging17:54 The Role of Folistatin and Telomerase in Aging21:04 Preventative Medicine and Gene Therapy24:02 Future of Gene Therapy and Embryo Editing27:08 The Ethics of Gene Editing and Parental Choices29:54 Preparing for a Multi-Planetary Future39:40 Exploring the Future of Space Travel40:08 The Importance of Safe Space Habitation41:06 Gene Therapy and Aging: A Deeper Dive42:52 Telomeres and Their Role in Longevity46:00 Cancer and Telomerase: Debunking Myths47:55 Hyperbaric Oxygen Therapy: Potential Benefits51:11 Balancing Regeneration and Cellular Division53:26 Pioneering Gene Therapy: A Personal Journey58:27 Measuring the Impact of Gene Therapy01:03:11 Skincare and Longevity: A Personal Approach01:10:24 Philosophy of Longevity: Balancing Life and Health01:14:05 Empowerment Through Gene Therapy for Women

In this final episode of our three-part series, we welcome back Dr. Bill Andrews, world-renowned telomere scientist and founder of Sierra Sciences. If you've been captivated by the journey through telomere science so far, you won't want to miss this deep dive into the future of telomerase research and its groundbreaking potential to reverse ageing at the genetic level. In this episode, Dr. Andrews reflects on the progress made in telomere science and shares his latest insights on how telomerase activation could become a mainstream therapy for longevity and disease prevention. He also unpacks the challenges, opportunities, and what lies ahead in the quest for cellular rejuvenation. Key Discussion Points:  Telomerase Activation – Practical Applications & Next Steps What widespread telomerase activation could mean for ageing and chronic disease prevention. How telomerase therapies might revolutionise healthcare in the next decade.  New Discoveries in Telomere Research The most recent advancements and promising compounds for telomerase activation. Understanding the role of telomeres in age-related diseases and how targeting them may prevent or reverse these conditions.  Balancing Safety & Innovation Regulatory and safety considerations for bringing telomerase activators to market. How to stay informed and support the development of telomerase-based therapies.  Longevity Science & Society – What's Next? The ethical and societal implications of dramatically extending human lifespan. Addressing skepticism and dispelling myths around telomerase research. What You'll Learn in This Episode: ✅ The difference between theoretical longevity interventions and those closest to clinical application. ✅ How telomerase research aligns with other emerging fields of longevity science. ✅ Why understanding telomeres is key to unlocking better healthspan and longer life. ✅ The real-world implications of reversing cellular aging and how you can be part of the movement. About Dr. Bill Andrews: Dr. Andrews is a molecular biologist, biotech pioneer, and ultramarathon runner who has dedicated over 30 years to the study of telomeres and telomerase. He holds more than 50 U.S. patents related to telomerase activation and continues to push the boundaries of what's possible in longevity science through his work at Sierra Sciences. Dr. Andrews has been featured in Popular Science, The Today Show, and documentaries like The Immortalists,  where he co-stars with Dr. Aubrey de Grey.

In this riveting second installment of our three-part series, Dr. Bill Andrews, one of the world's foremost experts in telomere science, returns to dive deeper into the groundbreaking research on telomerase activation. If you were fascinated by Part 1, this episode takes the conversation to the next level—exploring cutting-edge advancements, the latest discoveries, and what it truly means to reverse cellular aging. Dr. Andrews, founder of Sierra Sciences, has dedicated his career to decoding the mechanisms behind telomere shortening and how activating telomerase could hold the key to longevity. This episode unpacks new breakthroughs in telomerase research and the practical applications that could change the way we approach aging and disease prevention. Key Discussion Points:

In this fascinating first installment of a three-part series, we dive deep into the groundbreaking world of telomere science with Dr. Bill Andrews, a pioneering researcher in the field of ageing and longevity. Known for his revolutionary work on telomeres and their role in cellular aging, Dr. Andrews shares insights into how his research is paving the way for the ultimate goal: curing aging. Dr. Andrews, the founder of Sierra Sciences, has dedicated his life to understanding the root causes of ageing at the molecular level. This episode covers the basics of telomeres, the science behind their shortening, and why maintaining telomere length is essential for longevity and disease prevention. Key Discussion Points: What Are Telomeres? Telomeres are protective caps at the ends of chromosomes that safeguard our genetic material during cell division. As we age, telomeres shorten, leading to cellular dysfunction and ageing. Why Telomeres Matter in Aging: Telomere shortening is a major driver of ageing and age-related diseases. Dr. Andrews explains the link between telomeres and cellular senescence, inflammation, and chronic illnesses. Dr. Bill Andrews' Mission: The story behind Sierra Sciences, a biotechnology company dedicated to discovering drugs that activate the telomerase enzyme. Telomerase can rebuild and lengthen telomeres, potentially reversing cellular aging. The Science of Telomerase Activation: Current progress in identifying compounds that safely activate telomerase. Challenges and breakthroughs in the quest to develop anti-ageing therapies. Ethics and Implications of Curing Aging: Dr. Andrews discusses the societal, ethical, and philosophical implications of extending human lifespan. Addressing misconceptions about anti-ageing science. What You Will Learn: The fundamental role of telomeres in ageing and disease. How telomerase activation could revolutionise health and longevity. The current state of telomere research and its future potential. The challenges and ethical questions surrounding anti-ageing technologies. Don't miss the next episode in this series, where Dr. Andrews delves deeper into telomerase activation and the latest breakthroughs in curing aging. Subscribe to "Pushing the Limits" and share this episode with anyone passionate about health, science, and longevity! Bio: Dr. Bill Andrews is a molecular biologist, inventor, and renowned expert in the field of telomere science. He has over three decades of experience in biotech, including significant contributions to telomerase research. Dr. Andrews holds over 50 U.S. patents related to telomerase activation and has authored numerous scientific papers. Through his work at Sierra Sciences, he aims to unlock the secrets of human longevity and help people live healthier, longer lives. As a scientist, athlete, and executive, Bill continually pushes the envelope and challenges convention. He has been featured in Popular Science, The Today Show, and numerous documentaries on the topic of life extension including, most recently, the movie The Immortalists in which he co-stars with Dr. Aubrey de Grey.  Bill has been a medical researcher in biotech since 1981, focusing on cancer, heart disease, and inflammation research, though his passion has always been ageing. In the early-to-mid 1990s, while at Geron Corporation, Bill led the research to discover both the RNA and protein components of the human enzyme called telomerase. This enzyme is responsible for preventing telomeres from shortening in human reproductive cells, and this is why our children are born younger than we are even though they come from our old cells. Inducing this enzyme to lengthen telomeres in all our cells, not just our reproductive cells, to reverse aging and declining health due to aging, is the principal goal of Sierra Sciences and Sierra Holdings. Website: https://sierrasci.com/ The Immortalists Movie: https://theimmortalists.com/watch/ Best Choice Medicine petition, that you can sign today: https://www.bestchoicemedicine.com/  

Women drink less... if you ask them to visualize alcohol? Also, the yucky trick gossipers use to make you think they're kind — and why iron in red meat may be causing cancer (in your bottom).

Telomeres are structures made from DNA sequences and proteins, and they are found at the ends of chromosomes. In effect, they cap and protect the end of a chromosome. Telomerase is an enzyme that adds DNA to the ends of chromosomes, and it is reactivated in most cancers. Most human tumors not only express telomerase but also have very short telomeres. This makes telomerase a prime target for cancer therapies. MAIA Biotechnology is focused on the pioneering approach of telomere targeting through its lead therapeutic strategy, THIO. Currently, MAIA is making strides with THIO in a phase 2 clinical trial aimed at combating high-risk non-small cell lung cancer (NSCLC). THIO targets telomerase, thus disrupting cancer cells' vital structures, leading to their rapid demise. To tell us about MAIA's groundbreaking work, and the relationships between telomeres, telomerase and cancer, is the CEO and chairman of the company, Vlad Vitoc.01:16-02:13: About MAIA Biotechnology02:13-06:24: What is the role of telomerase in cancer?06:24-07:02: Do other factors affect telomeres?07:02-08:42: How does your therapy, THIO, work?08:42-09:08: Safety of THIO09:08-10:54: How is it administered?10:54-11:04: Are there other companies working on this?11:04-12;14: What else is in the MAIA pipeline?12:14-17:18: MAIA clinical trials17:18-18:19: Could THIO be a preventative treatment?18:19-19:46: Is there a lot of research on telomeres and telomerase?19:46-21:06: Are there cancers that are not telomerase positive?21:06-21:41: What is the future for telomere-targeting therapies?21:41-23:14: Are there any challenges?23:14-25:40: Is word spreading about your treatments?Interested in being a sponsor of an episode of our podcast? Discover how you can get involved here! Stay updated by subscribing to our newsletter

Das neue Molekül TAC ist eine Sensation! Wie es uns verjüngen könnte und was die Telomere überhaupt sind, erkläre ich euch in dieser kurzen Bonusfolge. Das Spannende Interview mit Prof. Dr. Lennard Rudolph könnt ihr euch hier anhören: https://link.stayoung.de/STY-131 Du interessierst dich für Gesunde Langlebigkeit (Longevity) und möchtest ein Leben lang gesund und fit bleiben, dann folge mir auch auf den sozialen Kanälen bei Instagram, TikTok, Facebook oder Youtube. https://www.instagram.com/nina.ruge.official https://www.tiktok.com/@nina.ruge.official https://www.facebook.com/NinaRugeOffiziell https://www.youtube.com/channel/UCOe2d1hLARB60z2hg039l9g   Disclaimer: Ich bin keine Ärztin und meine Inhalte ersetzen keine medizinische Beratung. Bei gesundheitlichen Fragen wende dich bitte an deinen Arzt/deine Ärztin.   STY-131

“My long-term goal is to model the pathways involved in human aging in order to develop therapeutic interventions. I organize an annual aging conference in the Midwestern United States with the dual goal of promoting the aging as an adaptation theory and promoting the aging as a disease mindset. The conference website is curing-aging.com.” Check out these other great views as well:Interview with Aubrey De Grey: https://youtu.be/DHvoPlcWwg4Interview with George Church: https://youtu.be/yNplpykf0B4Interview with Lisa Fabiny-Kiser: https://youtu.be/bE5jEGE5-OMInterview with Matt Kaeberlein: https://youtu.be/9QJ_ak3a05QInterview with Nir Barzilai : https://youtu.be/LuOAShcjOt0Interview with Michael Levin : https://youtu.be/5XvDdbYzwf8. PODCAST INFO:The Learning With Lowell show is a series for the everyday mammal. In this show we'll learn about leadership, science, and people building their change into the world. The goal is to dig deeply into people who most of us wouldn't normally ever get to hear. The Host of the show – Lowell Thompson- is a lifelong autodidact, serial problem solver, and founder of startups. LINKSSpotify: https://open.spotify.com/show/66eFLHQclKe5p3bMXsCTRHRSS: https://www.learningwithlowell.com/feed/podcast/Youtube: https://www.youtube.com/channel/UCzri06unR-lMXbl6sqWP_-QYoutube clips: https://www.youtube.com/channel/UC-B5x371AzTGgK-_q3U_KfAWebsite: https://www.learningwithlowell.com David Katz linkshttps://www.linkedin.com/in/davidwarrenkatz/https://www.youtube.com/watch?v=zhbOo_INMwg&t=65s&ab_channel=CuringAginghttps://www.curing-aging.com/ Timestamps00:00 start00:20 Programed aging hypothesis explained01:20 Michael Levin / bioelectricity02:15 Telomerase / concerns around copies of copies04:15 Ability for immortality in animals04:44 Immortal jellyfish06:02 Butterfly brains06:40 Programmed aging in practice for therapies07:16 FDA aging as a disease08:33 Curing aging objectionable09:15 We need to work against our bodies10:18 Fasting / Michael Rae / Caloric restriction11:55 Highly against Richard Dawkins selfish gene and ideas around evolution13:20 Start of slides13:50 Why do we age / David's argument18:20 Different types of aging23:20 Induce damage to test hypothesis25:10 David St Clair work26:20 Evolution has consistently selected for aging29:20 Aging and cancer30:00 exponential population growth31:00 Evolution as an ecological thing32:00 Animals getting bigger and smaller on small island / evolution as multivariable equation35:11 Mole Rats and rats36:25 people who get castrated live longer37:22 Bryan Johnson / interfering with body38:00 Testosterone / women live longer39:22 Mechanism of the body working against itself40:15 Easy interventions / keeping track of time for puberty, death, etc44:30 Squirrels having a year long internal clock46:00 Uniform life events / aging clock / evidence that convinces people50:50 ATF4 Pathway / muscle mass52:00 Not even trying to make therapies ATF454:40 Developing therapies against the body55:30 VCs at conference56:10 Exploring this hypothesis58:40 Tricking body to “think” it's younger59:10 Aubrey De Grey like hallmarks of aging clock1:00:00 Epigenetic clocks / biologic clocks01:01:30 Disrupting dreams / sleep01:02:50 Sleep affecting aging01:04:08 People who stop sleeping die within a number of weeks01:04:40 Does the biological clock have state and turning it back01:10:20 Steel man argument against the Programed aging hypothesis01:10:55 A good case for the clock / time of day, year, and stage of year01:13:00 Dolphins and sleep01:13:30 Target therapy with this theory01:15:40 Children's hospital01:16:05 Kids better able to fight off cancer / medicine divided01:17:11 PhD Tensor decomposition presentation / fundamental relationship of matrices01:18:40 implications and pushback for the tensor decomposition01:19:30 What are the trade offs / stop measuring algorithms based off complexity01:21:18 Real life example / chromosomes01:24:30 SENS and the human genome li...

A new drug is approved for MDS. While some will likely benefit from this new agent, the more enticing news is that inhibiting telomerase may be an attractive target for many malignancies.

In this podcast, Thomas Czech, Distinguished Professor at the University of Colorado, Boulder, with a lineage of remarkable contributions on RNA, ribozyme, and telomeres, discuss why RNA is so incredibly versatile.Video snippet from our conversation. Full videos of all Ground Truths podcasts can be seen on YouTube here. The audios are also available on Apple and Spotify.Transcript with links to the audio and external linksEric Topol (00:07):Well, hello, this is Eric Topol from Ground Truths, and it's really a delight for me to welcome Tom Cech who just wrote a book, the Catalyst, and who is a Nobel laureate for his work in RNA. And is at the University of Colorado Boulder as an extraordinary chemist and welcome Tom.Tom Cech (00:32):Eric, I'm really pleased to be here.The RNA GuyEric Topol (00:35):Well, I just thoroughly enjoyed your book, and I wanted to start out, if I could, with a quote, which gets us right off the story here, and let me just get to it here. You say, “the DNA guy would need to become an RNA guy. Though I didn't realize it at the time, jumping ship would turn out to be the most momentous decision in my life.” Can you elaborate a bit on that?Tom Cech (01:09):As a graduate student at Berkeley, I was studying DNA and chromosomes. I thought that DNA was king and really somewhat belittled the people in the lab next door who were working on RNA, I thought it was real sort of second fiddle material. Of course, when RNA is acting just as a message, which is an important function, a critical function in all life on earth, but still, it's a function that's subservient to DNA. It's just copying the message that's already written in the playbook of DNA. But little did I know that the wonders of RNA were going to excite me and really the whole world in unimaginable ways.Eric Topol (02:00):Well, they sure have, and you've lit up the world well before you had your Nobel Prize in 1989 was Sid Altman with ribozyme. And I think one of the things that struck me, which are so compelling in the book as I think people might know, it's divided in two sections. The first is much more on the biology, and the second is much more on the applications and how it's changing the world. We'll get into it particularly in medicine, but the interesting differentiation from DNA, which is the one trick pony, as you said, all it does is store stuff. And then the incredible versatility of RNA as you discovered as a catalyst, that challenging dogma, that proteins are supposed to be the only enzymes. And here you found RNA was one, but also so much more with respect to genome editing and what we're going to get into here. So I thought what we might get into is the fact that you kind of went into the scum of the pond with this organism, which by the way, you make a great case for the importance of basic science towards the end of the book. But can you tell us about how you, and then of course, many others got into the Tetrahymena thermophila, which I don't know that much about that organism.Tom Cech (03:34):Yeah, it's related to Tetrahymena is related to paramecium, which is probably more commonly known because it's an even larger single celled animal. And therefore, in an inexpensive grade school microscope, kids can look through and see these ciliated protozoa swimming around on a glass slide. But I first learned about them when I was a postdoc at MIT and I would drive down to Joe Gall's lab at Yale University where Liz Blackburn was a postdoc at the time, and they were all studying Tetrahymena. It has the remarkable feature that it has 10,000 identical copies of a particular gene and for a higher organism, one that has its DNA in the nucleus and does its protein synthesis in the cytoplasm. Typically, each gene's present in two copies, one from mom, one from dad. And if you're a biochemist, which I am having lots of stuff is a real advantage. So 10,000 copies of a particular gene pumping out RNA copies all the time was a huge experimental advantage. And that's what I started working on when I started my own lab at Boulder.Eric Topol (04:59):Well, and that's where, I guess the title of the book, the Catalyst ultimately, that grew into your discovery, right?Tom Cech (05:08):Well, at one level, yes, but I also think that the catalyst in a more general conversational sense means just facilitating life in this case. So RNA does much more than just serve as a biocatalyst or a message, and we'll get into that with genome editing and with telomerase as well.The Big Bang and 11 Nobel Prizes on RNA since 2000Eric Topol (05:32):Yes, and I should note that as you did early in the book, that there's been an 11 Nobel prize awardees since 2000 for RNA work. And in fact, we just had Venki who I know you know very well as our last podcast. And prior to that, Kati Karikó, Jennifer Doudna who worked in your lab, and the long list of people working RNA in the younger crowd like David Liu and Fyodor Urnov and just so many others, we need to have an RNA series because it's just exploding. And that one makes me take you back for a moment to 2007. And when I was reading the book, it came back to me about the Economist cover. You may recall almost exactly 17 years ago. It was called the Biology's Big Bang – Unravelling the secrets of RNA. And in that, there was a notable quote from that article. Let me just get to that. And it says, “it is probably no exaggeration to say that biology is now undergoing its neutron moment.”(06:52):This is 17 years ago. “For more than half a century the fundamental story of living things has been a tale of the interplay between genes, in the form of DNA, and proteins, which is genes encode and which do the donkey work of keeping living organisms living. The past couple of years, 17 years ago, however, has seen the rise and rise of a third type of molecule, called RNA.” Okay, so that was 2007. It's pretty extraordinary. And now of course we're talking about the century of biology. So can you kind of put these last 17 years in perspective and where we're headed?Tom Cech (07:34):Well, Eric, of course, this didn't all happen in one moment. It wasn't just one big bang. And the scientific community has been really entranced with the wonders of RNA since the 1960s when everyone was trying to figure out how messenger RNA stored the genetic code. But the general public has been really kept in the dark about this, I think. And as scientists, were partially to blame for not reaching out and sharing what we have found with them in a way that's more understandable. The DNA, the general public's very comfortable with, it's the stuff of our heredity. We know about genetic diseases, about tracing our ancestry, about solving crimes with DNA evidence. We even say things like it's in my DNA to mean that it's really fundamental to us. But I think that RNA has been sort of kept in the closet, and now with the mRNA vaccines against Covid-19, at least everyone's heard of RNA. And I think that that sort of allowed me to put my foot in the door and say, hey, if you were curious about the mRNA vaccines, I have some more stories for you that you might be really interested in.RNA vs RNAEric Topol (09:02):Yeah, well, we'll get to that. Maybe we should get to that now because it is so striking the RNA versus RNA chapter in your book, and basically the story of how this RNA virus SARS-CoV-2 led to a pandemic and it was fought largely through the first at scale mRNA nanoparticle vaccine package. Now, that takes us back to some seminal work of being able to find, giving an mRNA to a person without inciting massive amount of inflammation and the substitution of pseudouridine or uridine in order to do that. Does that really get rid of all the inflammation? Because obviously, as you know, there's been some negativism about mRNA vaccines for that and also for the potential of not having as much immune cell long term activation. Maybe you could speak to that.Tom Cech (10:03):Sure. So the discovery by Kati Karikó and Drew Weissman of the pseudouridine substitution certainly went a long way towards damping down the immune response, the inflammatory response that one naturally gets with an RNA injection. And the reason for that is that our bodies are tuned to be on the lookout for foreign RNA because so many viruses don't even mess with DNA at all. They just have a genome made of RNA. And so, RNA replicating itself is a danger sign. It means that our immune system should be on the lookout for this. And so, in the case of the vaccination, it's really very useful to dampen this down. A lot of people thought that this might make the mRNA vaccines strange or foreign or sort of a drug rather than a natural substance. But in fact, modified nucleotides, nucleotides being the building blocks of RNA, so these modified building blocks such as pseudoU, are in fact found in natural RNAs more in some than in others. And there are about 200 modified versions of the RNA building blocks found in cells. So it's really not an unusual modification or something that's all that foreign, but it was very useful for the vaccines. Now your other question Eric had to do with the, what was your other question, Eric?Eric Topol (11:51):No, when you use mRNA, which is such an extraordinary way to get the spike protein in a controlled way, exposed without the virus to people, and it saved millions of lives throughout the pandemic. But the other question is compared to other vaccine constructs, there's a question of does it give us long term protective immunity, particularly with T cells, both CD8 cytotoxic, maybe also CD4, as I know immunology is not your main area of interest, but that's been a rub that's been put out there, that it isn't just a weaning of immunity from the virus, but also perhaps that the vaccines themselves are not as good for that purpose. Any thoughts on that?Tom Cech (12:43):Well, so my main thought on that is that this is a property of the virus more than of the vaccine. And respiratory viruses are notoriously hard to get long-term immunity. I mean, look at the flu virus. We have to have annual flu shots. If this were like measles, which is a very different kind of virus, one flu shot would protect you against at least that strain of flu for the rest of your life. So I think the bad rap here is not the vaccine's fault nearly as much as it's the nature of respiratory viruses.RNA And Aging Eric Topol (13:27):No, that's extremely helpful. Now, let me switch to an area that's really fascinating, and you've worked quite a bit on the telomerase story because this is, as you know, being pursued quite a bit, has thought, not just because telomeres might indicate something about biologic aging, but maybe they could help us get to an anti-aging remedy or whatever you want to call it. I'm not sure if you call it a treatment, but tell us about this important enzyme, the role of the RNA building telomeres. And maybe you could also connect that with what a lot of people might not be familiar with, at least from years ago when they learned about it, the Hayflick limit.Tom Cech (14:22):Yes. Well, Liz Blackburn and Carol Greider got the Nobel Prize for the discovery of telomerase along with Jack Szostak who did important initial work on that system. And what it does is, is it uses an RNA as a template to extend the ends of human chromosomes, and this allows the cell to keep dividing without end. It gives the cell immortality. Now, when I say immortality, people get very excited, but I'm talking about immortality at the cellular level, not for the whole organism. And in the absence of a mechanism to build out the ends of our chromosomes, the telomeres being the end of the chromosome are incompletely replicated with each cell division. And so, they shrink over time, and when they get critically short, they signal the cell to stop dividing. This is what is called the Hayflick limit, first discovered by Leonard Hayflick in Philadelphia.(15:43):And he, through his careful observations on cells, growing human cells growing in Petri dishes, saw that they could divide about 50 times and then they wouldn't die. They would just enter a state called senescence. They would change shape, they would change their metabolism, but they would importantly quit dividing. And so, we now see this as a useful feature of human biology that this protects us from getting cancer because one of the hallmarks of cancer is immortality of the tumor cells. And so, if you're wishing for your telomeres to be long and your cells to keep dividing, you have to a little bit be careful what you wish for because this is one foot in the door for cancer formation.Eric Topol (16:45):Yeah, I mean, the point is that it seems like the body and the cell is smart to put these cells into the senescent state so they can't divide anymore. And one of the points you made in the book that I think is worth noting is that 90% of cancers have the telomerase, how do you say it?Tom Cech (17:07):Telomerase.Eric Topol (17:08):Yeah, reactivate.Tom Cech (17:09):Right.Eric Topol (17:10):That's not a good sign.Tom Cech (17:12):Right. And there are efforts to try to target telomerase enzyme for therapeutic purposes, although again, it's tricky because we do have stem cells in our bodies, which are the exception to the Hayflick limit rule. They do still have telomerase, they still have to keep dividing, maybe not as rapidly as a cancer cell, but they still keep dividing. And this is critical for the replenishment of certain worn out tissues in our such as skin cells, such as many of our blood cells, which may live only 30 days before they poop out. That's a scientific term for needing to be replenished, right?Eric Topol (18:07):Yeah. Well, that gets me to the everybody's, now I got the buzz about anti-aging, and whether it's senolytics to get rid of these senescent cells or whether it's to rejuvenate the stem cells that are exhausted or work on telomeres, all of these seem to connect with a potential or higher risk of cancer. I wonder what your thoughts are as we go forward using these various biologic constructs to be able to influence the whole organism, the whole human body aging process.Tom Cech (18:47):Yes. My view, and others may disagree is that aging is not an affliction. It's not a disease. It's not something that we should try to cure, but what we should work on is having a healthy life into our senior years. And perhaps you and I are two examples of people who are at that stage of our life. And what we would really like is to achieve, is to be able to be active and useful to society and to our families for a long period of time. So using the information about telomerase, for example, to help our stem cells stay healthy until we are, until we're ready to cash it in. And for that matter on the other side of the coin, to try to inhibit the telomerase in cancer because cancer, as we all know, is a disease of aging, right? There are young people who get cancer, but if you look at the statistics, it's really heavily weighted towards people who've been around a long time because mutations accumulate and other damage to cells that would normally protect against cancer accumulates. And so, we have to target both the degradation of our stem cells, but also the occurrence of cancer, particularly in the more senior population. And knowing more about RNA is really helpful in that regard.RNA DrugsEric Topol (20:29):Yeah. Well, one of the things that comes across throughout the book is versatility of RNA. In fact, you only I think, mentioned somewhere around 12 or 14 of these different RNAs that have a million different shapes, and there's so many other names of different types of RNAs. It's really quite extraordinary. But one of the big classes of RNAs has really hit it. In fact, this week there are two new interfering RNAs that are having extraordinary effects reported in the New England Journal on all the lipids, abnormal triglycerides and LDL cholesterol, APOC3. And can you talk to us about this interfering the small interfering RNAs and how they become, you've mentioned in the book over 400 RNAs are in the clinic now.Tom Cech (21:21):Yeah, so the 400 of course is beyond just the siRNAs, but these, again, a wonderful story about how fundamental science done just to understand how nature works without any particular expectation of a medical spinoff, often can have the most phenomenal and transformative effects on medicine. And this is one of those examples. It came from a roundworm, which is about the size of an eyelash, which a scientist named Sydney Brenner in England had suggested would be a great experimental organism because the entire animal has only about a thousand cells, and it's transparent so we can look at, see where the cells are, we can watch the worm develop. And what Andy Fire and Craig Mello found in this experimental worm was that double-stranded RNA, you think about DNA is being double-stranded and RNA as being single stranded. But in this case, it was an unusual case where the RNA was forming a double helix, and these little pieces of double helical RNA could turn off the expression of genes in the worm.(22:54):And that seemed remarkable and powerful. But as often happens in biology, at least for those of us who believe in evolution, what goes for the worm goes for the human as well. So a number of scientists quickly found that the same process was going on in the human body as a natural way of regulating the expression of our genes, which means how much of a particular gene product is actually going to be made in a particular cell. But not only was it a natural process, but you could introduce chemically synthesized double helical RNAs. There are only 23 base pairs, 23 units of RNA long, so they're pretty easy to chemically synthesize. And that once these are introduced into a human, the machinery that's already there grabs hold of them and can be used to turn off the expression of a disease causing RNA or the gene makes a messenger RNA, and then this double-stranded RNA can suppress its action. So this has become the main company that is known for doing this is Alnylam in Boston, Cambridge. And they have made quite a few successful products based on this technology.Eric Topol (24:33):Oh, absolutely. Not just for amyloidosis, but as I mentioned these, they even have a drug that's being tested now, as you know that you could take once or twice a year to manage your blood pressure. Wouldn't that be something instead of a pill every day? And then of course, all these others that are not just from Alnylam, but other companies I wasn't even familiar with for managing lipids, which is taking us well beyond statins and these, so-called PCSK9 monoclonal antibodies, so it's really blossoming. Now, the other group of RNA drugs are antisense drugs, and it seemed like they took forever to warm up, and then finally they hit. And can you distinguish the antisense versus the siRNA therapeutics?Tom Cech (25:21):Yes, in a real general sense, there's some similarity as well as some differences, but the antisense, what are called oligonucleotides, whoa, that's a big word, but oligo just means a few, right? And nucleotides is just the building blocks of nucleic acid. So you have a string of a few of these. And again, it's the power of RNA that it is so good at specifically base pairing only with matching sequences. So if you want to match with a G in a target messenger RNA, you put a C in the antisense because G pairs with C, if you want to put an A, if want to match with an A, you put a U in the antisense because A and U form a base pair U is the RNA equivalent of T and DNA, but they have the same coding capacity. So any school kid can write out on a notepad or on their laptop what the sequence would have to be of an antisense RNA to specifically pair with a particular mRNA.(26:43):And this has been, there's a company in your neck of the woods in the San Diego area. It started out with the name Isis that turned out to be the wrong Egyptian God to name your company after, so they're now known as Ionis. Hopefully that name will be around for a while. But they've been very successful in modifying these antisense RNAs or nucleic acids so that they are stable in the body long enough so that they can pair with and thereby inhibit the expression of particular target RNAs. So it has both similarities and differences from the siRNAs, but the common denominator is RNA is great stuff.RNA and Genome EditingEric Topol (27:39):Well, you have taken that to in catalyst, the catalyst, you've proven that without a doubt and you and so many other extraordinary scientists over the years, cumulatively. Now, another way to interfere with genes is editing. And of course, you have a whole chapter devoted to not just well CRISPR, but the whole genome editing field. And by the way, I should note that I forgot because I had read the Codebreaker and we recently spoke Jennifer Doudna and I, that she was in your lab as a postdoc and you made some wonderful comments about her. I don't know if you want to reflect about having Jennifer, did you know that she was going to do some great things in her career?Tom Cech (28:24):Oh, there was no question about it, Eric. She had been a star graduate student at Harvard, had published a series of breathtaking papers in magazines such as Science and Nature already as a graduate student. She won a Markey fellowship to come to Colorado. She chose a very ambitious project trying to determine the molecular structures of folded RNA molecules. We only had one example at the time, and that was the transfer RNA, which is involved in protein synthesis. And here she was trying these catalytic RNAs, which we had discovered, which were much larger than tRNA and was making great progress, which she finished off as an assistant professor at Yale. So what the general public may not know was that in scientific, in the scientific realm, she was already highly appreciated and much awarded before she even heard anything about CRISPR.Eric Topol (29:38):Right. No, it was a great line you have describing her, “she had an uncanny talent for designing just the right experiment to test any hypothesis, and she possessed more energy and drive than any scientist I'd ever met.” That's pretty powerful. Now getting into CRISPR, the one thing, it's amazing in just a decade to see basically the discovery of this natural system to then be approved by FDA for sickle cell disease and beta thalassemia. However, the way it exists today, it's very primitive. It's not actually fixing the gene that's responsible, it's doing a workaround plan. It's got double strand breaks in the DNA. And obviously there's better ways of editing, which are going to obviously involve RNA epigenetic editing, if you will as well. What is your sense about the future of genome editing?Tom Cech (30:36):Yeah, absolutely, Eric. It is primitive right now. These initial therapies are way too expensive as well to make them broadly applicable to the entire, even in a relatively wealthy country like the United States, we need to drive the cost down. We need to get them to work, we need to get the process of introducing them into the CRISPR machinery into the human body to be less tedious and less time consuming. But you've got to start somewhere. And considering that the Charpentier and Doudna Nobel Prize winning discovery was in 2012, which is only a dozen years ago, this is remarkable progress. More typically, it takes 30 years from a basic science discovery to get a medical product with about a 1% chance of it ever happening. And so, this is clearly a robust RNA driven machine. And so, I think the future is bright. We can talk about that some more, but I don't want to leave RNA out of this conversation, Eric. So what's cool about CRISPR is its incredible specificity. Think of the human genome as a million pages of text file on your computer, a million page PDF, and now CRISPR can find one sentence out of that million pages that matches, and that's because it's using RNA, again, the power of RNA to form AU and GC base pairs to locate just one site in our whole DNA, sit down there and direct this Cas9 enzyme to cut the DNA at that site and start the repair process that actually does the gene editing.Eric Topol (32:41):Yeah, it's pretty remarkable. And the fact that it can be so precise and it's going to get even more precise over time in terms of the repair efforts that are needed to get it back to an ideal state. Now, the other thing I wanted to get into with you a bit is on the ribosome, because that applies to antibiotics and as you call it, the mothership. And I love this metaphor that you had about the ribosome, and in the book, “the ribosome is your turntable, the mRNA is the vinyl LP record, and the protein is the music you hear when you lower the needle.” Tell us more about the ribosome and the role of antibiotics.Tom Cech (33:35):So do you think today's young people will understand that metaphor?Eric Topol (33:40):Oh, they probably will. They're making a comeback. These records are making a comeback.Tom Cech (33:44):Okay. Yes, so this is a good analogy in that the ribosome is so versatile it's able to play any music that you feed at the right messenger RNA to make the music being the protein. So you can have in the human body, we have tens of thousands of different messenger RNAs. Each one threads through the same ribosome and spills out the production of whatever protein matches that mRNA. And so that's pretty remarkable. And what Harry Noller at UC Santa Cruz and later the crystallographers Venki Ramakrishnan, Tom Steitz, Ada Yonath proved really through their studies was that this is an RNA machine. It was hard to figure that out because the ribosome has three RNAs and it has dozens of proteins as well. So for a long time people thought it must be one of those proteins that was the heart and soul of the record player, so to speak.RNA and Antibiotics(34:57):And it turned out that it was the RNA. And so, when therefore these scientists, including Venki who you just talked to, looked at where these antibiotics docked on the ribosome, they found that they were blocking the key functional parts of the RNA. So it was really, the antibiotics knew what they were doing long before we knew what they were doing. They were talking to and obstructing the action of the ribosomal RNA. Why is this a good thing for us? Because bacterial ribosomes are just enough different from human ribosomes that there are drugs that will dock to the bacterial ribosomal RNA, throw a monkey wrench into the machine, prevent it from working, but the human ribosomes go on pretty much unfazed.Eric Topol (36:00):Yeah, no, the backbone of our antibiotics relies on this. So I think people need to understand about the two subunits, the large and the small and this mothership, and you illuminate that so really well in the book. That also brings me to phage bacteria phage, and we haven't seen that really enter the clinic in a significant way, but there seems to be a great opportunity. What's your view about that?Tom Cech (36:30):This is an idea that goes way back because since bacteria have their own viruses which do not infect human cells, why not repurpose those into little therapeutic entities that could kill, for example, what would we want to kill? Well, maybe tuberculosis has been very resistant to drugs, right? There are drug resistant strains of TB, yes, of TB, tuberculosis, and especially in immunocompromised individuals, this bug runs rampant. And so, I don't know the status of that. It's been challenging, and this is the way that biomedicine works, is that for every 10 good ideas, and I would say phage therapy for bacterial disease is a good idea. For every 10 such ideas, one of them ends up being practical. And the other nine, maybe somebody else will come along and find a way to make it work, but it hasn't been a big breakthrough yet.RNA, Aptamers and ProteinsEric Topol (37:54):Yeah, no, it's really interesting. And we'll see. It may still be in store. What about aptamers? Tell us a little bit more about those, because they have been getting used a lot in sorting out the important plasma proteins as therapies. What are aptamers and what do you see as the future in that regard?Tom Cech (38:17):Right. Well, in fact, aptamers are a big deal in Boulder because Larry Gold in town was one of the discoverers has a company making aptamers to recognize proteins. Jack Szostak now at University of Chicago has played a big role. And also at your own institution, Jerry Joyce, your president is a big aptamer guy. And you can evolution, normally we think about it as happening out in the environment, but it turns out you can also make it work in the laboratory. You can make it work much faster in the laboratory because you can set up test tube experiments where molecules are being challenged to perform a particular task, like for example, binding to a protein to inactivate it. And if you make a large community of RNA molecules randomly, 99.999% of them aren't going to know how to do this. What are the odds? Very low.(39:30):But just by luck, there will be an occasional molecule of RNA that folds up into a shape that actually fits into the proteins active sighting throws a monkey wrench into the works. Okay, so now that's one in a billion. How are you going to find that guy? Well, this is where the polymerase chain reaction, the same one we use for the COVID-19 tests for infection comes into play. Because if you can now isolate this needle in a haystack and use PCR to amplify it and make a whole handful of it, now you've got a whole handful of molecules which are much better at binding this protein than the starting molecule. And now you can go through this cycle several times to enrich for these, maybe mutagen it a little bit more to give it a little more diversity. We all know diversity is good, so you put a little more diversity into the population and now you find some guy that's really good at recognizing some disease causing protein. So this is the, so-called aptamer story, and they have been used therapeutically with some success, but diagnostically certainly they are extremely useful. And it's another area where we've had success and the future could hold even more success.Eric Topol (41:06):I think what you're bringing up is so important because the ability to screen that tens of thousands of plasma proteins in a person and coming up with as Tony Wyss-Coray did with the organ clocks, and this is using the SomaLogic technology, and so much is going on now to get us not just the polygenic risk scores, but also these proteomic scores to compliment that at our orthogonal, if you will, to understand risk of people for diseases so we can prevent them, which is fulfilling a dream we've never actually achieved so far.Tom Cech (41:44):Eric, just for full disclosure, I'm on the scientific advisory board of SomaLogic in Boulder. I should disclose that.Eric Topol (41:50):Well, that was smart. They needed to have you, so thank you for mentioning that. Now, before I wrap up, well, another area that is a favorite of mine is citizen science. And you mentioned in the book a project because the million shapes of RNA and how it can fold with all hairpin terms turns and double stranded and whatever you name it, that there was this project eteRNA that was using citizen scientists to characterize and understand folding of RNA. Can you tell us about that?RNA Folding and Citizen ScienceTom Cech (42:27):So my friend Rhiju Das, who's a professor at Stanford University, sort of adopted what had been done with protein folding by one of his former mentors, David Baker in Seattle, and had repurposed this for RNA folding. So the idea is to come up with a goal, a target for the community. Can you design an RNA that will fold up to look like a four pointed cross or a five pointed star? And it turned out that, so they made it into a contest and they had tens of thousands of people playing these games and coming up with some remarkable solutions. But then they got a little bit more practical, said, okay, that was fun, but can we have the community design something like a mRNA for the SARS-CoV-2 spike protein to make maybe a more stable vaccine? And quite remarkably, the community of many of whom are just gamers who really don't know much about what RNA does, were able to find some solutions. They weren't enormous breakthroughs, but they got a several fold, several hundred percent increase in stability of the RNA by making it fold more tightly. So I just find it to be a fascinating approach to science. Somebody of my generation would never think of this, but I think for today's generation, it's great when citizens can become involved in research at that level.Eric Topol (44:19):Oh, I think it's extraordinary. And of course, there are other projects folded and others that have exemplified this ability for people with no background in science to contribute in a meaningful way, and they really enjoy, it's like solving a puzzle. The last point is kind of the beginning, the origin of life, and you make a pretty strong case, Tom, that it was RNA. You don't say it definitively, but maybe you can say it here.RNA and the Origin of LifeTom Cech (44:50):Well, Eric, the origin of life happening almost 4 billion years ago on our primitive planet is sort of a historical question. I mean, if you really want to know what happened then, well, we don't have any video surveillance of those moments. So scientists hate to ever say never, but it's hard to sort of believe how we would ever know for sure. So what Leslie Orgel at the Salk Institute next to you taught me when I was a starting assistant professor is even though we'll never know for sure, if we can recapitulate in the laboratory plausible events that could have happened, and if they make sense chemically and biologically, then that's pretty satisfying, even if we can never be absolutely sure. That's what a number of scientists have done in this field is to show that RNA is sort of a, that all the chemistry sort of points to RNA as being something that could have been made under prebiotic conditions and could have folded up into a way that could solve the greatest of all chicken and egg problems, which came first, the informational molecule to pass down to the next generation or the active molecule that could copy that information.(46:32):So now that we know that RNA has both of those abilities, maybe at the beginning there was just this RNA world RNA copying itself, and then proteins came along later, and then DNA probably much more recently as a useful but a little bit boring of genetic information, right?Eric Topol (46:59):Yeah. Well, that goes back to that cover of the Economist 17 years ago, the Big Bang, and you got me convinced that this is a pretty strong story and candidate. Now what a fun chance to discuss all this with you in an extraordinary book, Tom. Did I miss anything that you want to bring up?Tom Cech (47:21):Eric, I just wanted to say that I not only appreciate our conversation, but I also appreciate all you are doing to bring science to the non-scientist public. I think people like me who have taught a lot of freshmen in chemistry, general chemistry, sort of think that that's the level that we need to aim at. But I think that those kids have had science in high school year after year. We need to aim at the parents of those college freshmen who are intelligent, who are intellectually curious, but have not had science courses in a long time. And so, I'm really joining with you in trying to avoid jargon as much as possible. Use simple language, use analogies and metaphors, and try to share the excitement of what we're doing in the laboratory with the populace.Eric Topol (48:25):Well, you sure did that it was palpable. And I thought about it when I read the book about how lucky it would be to be a freshman at the University of Boulder and be having you as the professor. My goodness. Well, thank you so much. This has been so much fun, Tom, and I hope everybody's going to get out there and read the Catalyst to get all the things that we didn't even get a chance to dive into. But this has been great and look forward to future interactions with you.Tom Cech (48:53):Take care, Eric.*********************Thanks for listening or reading this edition of Ground Truths.Please share this podcast with your friends and network. That tells me you found it informative and makes the effort in doing these worthwhile.All Ground Truths newsletters and podcast are free. Voluntary paid subscriptions all go to support Scripps Research. Many thanks for that—they greatly helped fund our summer internship programs for 2023 and 2024.Thanks to my producer Jessica Nguyen and Sinjun Balabanoff for audio and video support at Scripps Research.Note: you can select preferences to receive emails about newsletters, podcasts, or all I don't want to bother you with an email for content that you're not interested in. Get full access to Ground Truths at erictopol.substack.com/subscribe

Ronald DePinho, M.D., explains how telomerase, typically linked to telomere maintenance, serves as a transcriptional co-activator in the brain. Epigenetic repression of TERT, the gene for telomerase, occurs with aging, contributing to aging hallmarks like cellular senescence and inflammation. DePinho's team developed a compound that reactivates TERT, which, when administered to mice, reverses age-related changes. It restores cognitive function, reduces amyloid plaque, and alleviates inflammation. This suggests that maintaining TERT levels can counteract age-related cognitive decline and neurodegeneration, offering potential for treating neurodegenerative diseases like Alzheimer's. DePinho's work expands our understanding of telomerase's multifaceted role in aging and neurodegeneration, holding promise for interventions against these age-related processes. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 39071]

Ronald DePinho, M.D., explains how telomerase, typically linked to telomere maintenance, serves as a transcriptional co-activator in the brain. Epigenetic repression of TERT, the gene for telomerase, occurs with aging, contributing to aging hallmarks like cellular senescence and inflammation. DePinho's team developed a compound that reactivates TERT, which, when administered to mice, reverses age-related changes. It restores cognitive function, reduces amyloid plaque, and alleviates inflammation. This suggests that maintaining TERT levels can counteract age-related cognitive decline and neurodegeneration, offering potential for treating neurodegenerative diseases like Alzheimer's. DePinho's work expands our understanding of telomerase's multifaceted role in aging and neurodegeneration, holding promise for interventions against these age-related processes. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 39071]

Ronald DePinho, M.D., explains how telomerase, typically linked to telomere maintenance, serves as a transcriptional co-activator in the brain. Epigenetic repression of TERT, the gene for telomerase, occurs with aging, contributing to aging hallmarks like cellular senescence and inflammation. DePinho's team developed a compound that reactivates TERT, which, when administered to mice, reverses age-related changes. It restores cognitive function, reduces amyloid plaque, and alleviates inflammation. This suggests that maintaining TERT levels can counteract age-related cognitive decline and neurodegeneration, offering potential for treating neurodegenerative diseases like Alzheimer's. DePinho's work expands our understanding of telomerase's multifaceted role in aging and neurodegeneration, holding promise for interventions against these age-related processes. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 39071]

Ronald DePinho, M.D., explains how telomerase, typically linked to telomere maintenance, serves as a transcriptional co-activator in the brain. Epigenetic repression of TERT, the gene for telomerase, occurs with aging, contributing to aging hallmarks like cellular senescence and inflammation. DePinho's team developed a compound that reactivates TERT, which, when administered to mice, reverses age-related changes. It restores cognitive function, reduces amyloid plaque, and alleviates inflammation. This suggests that maintaining TERT levels can counteract age-related cognitive decline and neurodegeneration, offering potential for treating neurodegenerative diseases like Alzheimer's. DePinho's work expands our understanding of telomerase's multifaceted role in aging and neurodegeneration, holding promise for interventions against these age-related processes. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 39071]

Ronald DePinho, M.D., explains how telomerase, typically linked to telomere maintenance, serves as a transcriptional co-activator in the brain. Epigenetic repression of TERT, the gene for telomerase, occurs with aging, contributing to aging hallmarks like cellular senescence and inflammation. DePinho's team developed a compound that reactivates TERT, which, when administered to mice, reverses age-related changes. It restores cognitive function, reduces amyloid plaque, and alleviates inflammation. This suggests that maintaining TERT levels can counteract age-related cognitive decline and neurodegeneration, offering potential for treating neurodegenerative diseases like Alzheimer's. DePinho's work expands our understanding of telomerase's multifaceted role in aging and neurodegeneration, holding promise for interventions against these age-related processes. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 39071]

Ronald DePinho, M.D., explains how telomerase, typically linked to telomere maintenance, serves as a transcriptional co-activator in the brain. Epigenetic repression of TERT, the gene for telomerase, occurs with aging, contributing to aging hallmarks like cellular senescence and inflammation. DePinho's team developed a compound that reactivates TERT, which, when administered to mice, reverses age-related changes. It restores cognitive function, reduces amyloid plaque, and alleviates inflammation. This suggests that maintaining TERT levels can counteract age-related cognitive decline and neurodegeneration, offering potential for treating neurodegenerative diseases like Alzheimer's. DePinho's work expands our understanding of telomerase's multifaceted role in aging and neurodegeneration, holding promise for interventions against these age-related processes. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 39071]

Ronald DePinho, M.D., explains how telomerase, typically linked to telomere maintenance, serves as a transcriptional co-activator in the brain. Epigenetic repression of TERT, the gene for telomerase, occurs with aging, contributing to aging hallmarks like cellular senescence and inflammation. DePinho's team developed a compound that reactivates TERT, which, when administered to mice, reverses age-related changes. It restores cognitive function, reduces amyloid plaque, and alleviates inflammation. This suggests that maintaining TERT levels can counteract age-related cognitive decline and neurodegeneration, offering potential for treating neurodegenerative diseases like Alzheimer's. DePinho's work expands our understanding of telomerase's multifaceted role in aging and neurodegeneration, holding promise for interventions against these age-related processes. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 39071]

Ronald DePinho, M.D., explains how telomerase, typically linked to telomere maintenance, serves as a transcriptional co-activator in the brain. Epigenetic repression of TERT, the gene for telomerase, occurs with aging, contributing to aging hallmarks like cellular senescence and inflammation. DePinho's team developed a compound that reactivates TERT, which, when administered to mice, reverses age-related changes. It restores cognitive function, reduces amyloid plaque, and alleviates inflammation. This suggests that maintaining TERT levels can counteract age-related cognitive decline and neurodegeneration, offering potential for treating neurodegenerative diseases like Alzheimer's. DePinho's work expands our understanding of telomerase's multifaceted role in aging and neurodegeneration, holding promise for interventions against these age-related processes. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 39071]

Ronald DePinho, M.D., explains how telomerase, typically linked to telomere maintenance, serves as a transcriptional co-activator in the brain. Epigenetic repression of TERT, the gene for telomerase, occurs with aging, contributing to aging hallmarks like cellular senescence and inflammation. DePinho's team developed a compound that reactivates TERT, which, when administered to mice, reverses age-related changes. It restores cognitive function, reduces amyloid plaque, and alleviates inflammation. This suggests that maintaining TERT levels can counteract age-related cognitive decline and neurodegeneration, offering potential for treating neurodegenerative diseases like Alzheimer's. DePinho's work expands our understanding of telomerase's multifaceted role in aging and neurodegeneration, holding promise for interventions against these age-related processes. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 39071]

Ronald DePinho, M.D., explains how telomerase, typically linked to telomere maintenance, serves as a transcriptional co-activator in the brain. Epigenetic repression of TERT, the gene for telomerase, occurs with aging, contributing to aging hallmarks like cellular senescence and inflammation. DePinho's team developed a compound that reactivates TERT, which, when administered to mice, reverses age-related changes. It restores cognitive function, reduces amyloid plaque, and alleviates inflammation. This suggests that maintaining TERT levels can counteract age-related cognitive decline and neurodegeneration, offering potential for treating neurodegenerative diseases like Alzheimer's. DePinho's work expands our understanding of telomerase's multifaceted role in aging and neurodegeneration, holding promise for interventions against these age-related processes. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 39071]

In this weeks episode of "Pushing the Limits" Lisa gets to talk to a world leading anti-aging and longevity expert Dr Bill Lawrence who himself is 77 years old but has the telomere length (we explain what that aging biomarker in the show) of someone in their thirties. Dr. Lawrence has a Jurisprudence Degree (UCLA-Law), an MS in Psychology and a Ph.D. in Nutrition. Since 1990 his focus has been on slowing and reversing human biological aging. He has developed numerous science-based protocols focused on optimal aging for health professionals and individual clients.   Presently Dr. Lawrence is the administrator of two clinical studies to determine if human biological age can be reversed in collaboration with Dr Vladimir Khavinson of the Saint-Petersburg Institute of Bioregulation and Gerontology Dr Lawrence shares in this episode a presentation of the current study data (note the trial is still ongoing) and the exciting proof we can now REVERSE aging and promote long and healthier lives and reduce our risk of morbidity and mortality using Bioregulators  The science behind this is impressive and it's human trials. Dr Lawrence is reinforcing through his findings the research of Professor Khavinson who has been working on Bioregulators and doing the research on these for over 5 decades. I am excited to share this cutting edge information with you and to get going myself on the Bioregulators. BIO BILL LAWRENCE JD. MS, Ph.D. Dr. Lawrence is an American biogerontologist with a Jurisprudence Degree (UCLA-Law), an MS in Psychology, and a Ph.D. in Nutritional Science. For three decades, his focus has been human longevity research and interventions for optimal life and healthspan. He is the administrator of two Russian and American longevity clinical studies: Telomerase activation and DNA/Methylation modification. These studies use Khavinson Peptide Bioregulators developed by Prof. Vladimir Khavinson of the St. Petersburg Institute, for organ regeneration, mortality reduction and reversal of human aging biomarkers. In his presentation, Dr. Lawrence, as a scientist, will report  clinical study data and, as an attorney, evidence confirming Peptide Bioregulators are the only proven interventions supported by human studies that accomplish the above.  Dr. Lawrence is chronologically 77. His average telomere length, or “Cellular Age” is equivalent to a 23-year-old. His “Epigenetic Age” measured by the Horvath Epigenetic Clock (DNA/Methylation) reports a fifty percent reduction of all-cause mortality risk compared to his same-age peers.   Health Optimisation and Life Coaching with Lisa Tamati Lisa offers solution focused coaching sessions to help you find the right answers to your challenges. Topics Lisa can help with:  Lisa is a Genetics Practitioner, Health Optimisation Coach, High Performance and Mindset Coach. She is a qualified Ph360 Epigenetics coach and a clinician with The DNA Company and has done years of research into brain rehabilitation, neurodegenerative diseases and biohacking. She has extensive knowledge on such therapies as hyperbaric oxygen,  intravenous vitamin C, sports performance, functional genomics, Thyroid, Hormones, Cancer and much more. Testing Options Comprehensive Thyroid testing DUTCH Hormone testing Adrenal Testing Organic Acid Testing Microbiome Testing Cell Blueprint Testing Epigenetics Testing DNA testing Basic Blood Test analysis She can help you navigate the confusing world of health and medicine and can advocate for you. She can also advise on the latest research and where to get help if mainstream medicine hasn't got the answers you are searching for whether you are facing challenges from cancer to gut issues, from depression and anxiety, weight loss issues, from head injuries to burn out. Book you consultation with Lisa    Join our Patron program and support the show Pushing the Limits' has been free to air for over 8 years. Providing leading edge information to anyone who needs it. But we need help on our mission.  Please join our patron community and get exclusive member benefits (more to roll out later this year) and support this educational platform for the price of a coffee or two You can join by going to  Lisa's Patron Community   Lisa's Anti-Aging and Longevity Supplements  Lisa has spent years curating a very specialised range of exclusive longevity, health optimising supplements from leading scientists, researchers and companies all around the world.  This is an unprecedented collection. The stuff Lisa wanted for her mum but couldn't get in NZ. Check out the range at her LongLifeLabs shop   Subscribe to our popular Youtube channel  with over 600 videos, millions of views, a number of full length documentaries, and much more. You don't want to miss out on all the great content on our Lisa's youtube channel. Youtube   Order Lisa's Books My latest book Relentless chronicles the inspiring journey of 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. Order your copy here:  RELENTLESS - How A Mother & Daughter Defied The Odds   Our NMN Bio Flagship Longevity Range A range by molecular biologist Dr Elena Seranova NMN: Nicotinamide Mononucleotide, an NAD+ precursor 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, decreases dramatically 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 Aging We offer powerful third-party tested NAD+ boosting supplements so you can start your healthy ageing journey today. Shop now:  shop.lisatamati.com  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 Boost Your NAD+ Levels — Healthy Ageing: Redefined Cellular Health Energy & Focus Bone Density Skin Elasticity DNA Repair Cardiovascular Health Brain Health Metabolic Health Listen to the episodes with Dr Seranova on the show: https://www.lisatamati.com/podcast--dr-elena-seranova/ https://www.lisatamati.com/podcast--dr-elena-seranova-part-3/   Perfect Amino Supplement by Dr David Minkoff Introducing PerfectAmino PerfectAmino is an amino acid supplement that is 99% utilised by the body to make protein. PerfectAmino is 3-6x the protein of other sources with almost no calories. 100% vegan and non-GMO. The coated PerfectAmino tablets are a slightly different shape and have a natural, non-GMO, certified organic vegan coating on them so they will glide down your throat easily. Fully absorbed within 20-30 minutes! No other form of protein comes close to PerfectAminos Listen to the episode with Dr MInkoff here:  Ketone Products by HVMN The world's best  exogenous Ketone IQ Listen to the episode with Dr Latt Mansor Lisa's  ‘Fierce' Sports Jewellery Collection For Lisa's gorgeous and inspiring sports jewellery collection, 'Fierce', go to Jewellery   For Vielight Device Vielight brain photobiomodulation devices combine electrical engineering and neuroscience. To find out more about photobiomodulation, current studies underway and already completed and for the devices mentioned in this video go to www.vielight.com Use code "tamati" at checkout to get a 10% discount on any of their devices.   Enjoyed This Podcast? If you did, subscribe and share it with your friends! If you enjoyed tuning in, then leave us a review and share this with your family and friends. Have any questions? You can contact my team 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. Donate $3 to help Lisa and her team produce more great content https://www.buymeacoffee.com/LisaT To pushing the limits, Lisa and team

BILL LAWRENCE JD. MS, Ph.D.Dr. Lawrence is an American biogerontologist with a Jurisprudence Degree (UCLA-Law), an MS in Psychology, and a Ph.D. in Nutritional Science. For three decades, his focus has been human longevity research and interventions for optimal life and healthspan. Dr. Lawrence has been affiliated with the St. Petersburg Institute of Bioregulation and Gerontology (Russia) since 2015. He administers two Russian and American longevity clinical studies: Telomerase activationand DNA/Methylation modification.These studies use Khavinson Peptide Bioregulators, developed by Prof. Vladimir Khavinson of the St. Petersburg Institute, to reverse human aging.

In 2009 a new enzyme within the human DNA & chromosomes was discovered. It was this enzyme (Telomerase) that now shows us how cells break down and how we can slow that process extending the average human lifespan well into 120+ years. My website with free audio download of my book: https://ungraduated.com Ungraduated Book for purchase: https://www.amazon.com/Ungraduated-Finding-dropping-outdated-systems-ebook/dp/B09SXCBY6R/ref=sr_1_1?crid=28QTYUU7T5BN4&keywords=ungraduated+book&qid=1655499090&sprefix=ungraduate%2Caps%2C122&sr=8-1 Join the Ungraduated Living Community: https://www.facebook.com/groups/454790476338234

Today, we get to explore gene therapy, and the possibilities for longevity with someone who is not only an expert in the field, but who actually tested the longevity gene therapy on herself. Elizabeth Parrish is an entrepreneur and founder and CEO of BioViva Sciences.LINK:Elizabeth Parrish - LIBioViva Science - WebsiteBioViva Science - YTTIMESTAMPS:01:04 - BioViva Sciences01:26 - Gene Therapy03:08 - Aging and Longevity03:25 - Cellular Level05:01 - Cellular Degeneration07:13 - Plasma Plasmapheresis08:46 - Beta thalassemia10:48- Alzheimer14:53 - Intra Nasal Spray15:36 - Cytomegalovirus34:03 - BioViva-science.com34:28 - info@BioViva-science.com----------#telomereattrition #genomicinstability #BioVivaScience #ElizabethParrish #longevity #info@BioViva-science.com #aging #genetherapy #Telomerase #stemcells#robertlufkinmd #drlufkin #robertlufkin #stephensideroff #drsideroff #stephensideroffphd #healthlongevitysecrets #pathlongevity*** CHECK OUT ROB AND STEVE'S MASTERCLASSES ***https://pathlongevity.com/masterclass*** CONNECT WITH ROBERT LUFKIN MD ON SOCIAL MEDIA ***Web: https://robertlufkinmd.com/Twitter: https://twitter.com/robertlufkinmdYoutube: https://www.youtube.com/RobertLufkinMDInstagram: https://www.instagram.com/robertlufkinmd/*** CONNECT WITH STEPHEN SIDEROFF PHD ON SOCIAL MEDIA ***Facebook: https://www.facebook.com/stephen.sideroffTwitter: https://twitter.com/DrSideroffInstagram: https://www.instagram.com/drstephensideroff/LinkedIn: https://www.linkedin.com/in/drstephensideroff/*** SPONSORSHIPS & BRANDS ***We do work with sponsors and brands. If you are interested in working with us for your health industry product or service, please contact us at:https://pathlongevity.com/contact-us/ NOTE: This is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have. Never disregard professional medical advice or delay in seeking it because of something you have seen here. Robert Lufkin MD may at any time and at its sole discretion change or replace the information available on this channel. To the extent permitted by mandatory law, Robert Lufkin MD shall not be liable for any direct, incidental, consequential, indirect or punitive damages arising out of access to or use of any content available on this channel, including viruses, regardless of the accuracy or completeness of any such content.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.09.527879v1?rss=1 Authors: Jensen, G. S., Beaulieu, A. N., Curtis, C. D., Passarelli, J., Blaszkiewicz, M., Thomas, S., Morin, T., Willows, J. W., Greco, C. W., Brennan, C. J., Aniapam, C., Caron, L., Alves, M. J., Lynes, M. D., Carlone, D. L., Breault, D. T., Townsend, K. L. Abstract: Telomerase reverse transcriptase (TERT) is expressed by quiescent adult stem cells (ASC) in numerous adult murine and human tissues, but has never been explored in the adult brain. Here, we demonstrate that TERT+ cells in the adult mouse brain represent a novel population of multipotent ASCs that are localized to numerous classical neuro/gliogenic niches (including the ventricular-subventricular zone, hypothalamus, and olfactory bulb), as well as more recently described regions of adult brain plasticity such as the meninges and choroid plexus. Using a direct-reporter mouse line, we found that TERT+ cells expressed known neural stem cell markers such as Nestin and Sox2, but not markers of committed stem/progenitor cells, nor markers of mature neuronal or glial cells. TERT+ ASCs rarely expressed the proliferation marker Ki67, and in vitro TERT+ cells lost TERT expression when activated by growth factors, together indicating a quiescent phenotype similar to what has been observed in other tissues. When cultured, TERT+ cells behaved like neural stem cells by forming neurospheres, which could proliferate and become more metabolically active once stimulated by growth factors. TERT+ cells were observed in numerous brain niches, particularly near the ventricles and cerebrospinal fluid barriers, but notably, TERT+ cells were never observed in the hippocampus. Lineage tracing of TERT+ cells in adult transgenic mice (mTERTrtTA::oTET-Cre::RosamTmG) revealed large-scale expansion of TERT+ progeny and differentiation to diverse cell types in multiple brain regions. For example, lineage-traced cells expressed markers of mature neurons, oligodendrocytes, astrocytes, ependymal cells, and choroid epithelial cells, thus demonstrating the striking multipotency of this stem cell population in basal tissue turnover of the adult brain. Together, these data demonstrate that TERT+ cells represent a novel population of multipotent stem cells that contribute to basal plasticity and regeneration in the adult mouse brain. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.19.524780v1?rss=1 Authors: Estep, K. N., Tobias, J. W., Fernandez, R. J., Beveridge, B. M., Johnson, F. B. Abstract: Although mechanisms of telomere protection are well-defined in differentiated cells, it is poorly understood how stem cells sense and respond to telomere dysfunction. Recent efforts have characterized the DNA damage response (DDR) following progressive telomere erosion in human pluripotent cells, yet the broader impact of telomeric double-strand breaks (DSBs) in these cells is poorly characterized. Here, we report on DNA damage signaling, cell cycle, and transcriptome-level changes in human induced pluripotent stem cells (iPSCs) in response to telomere-internal DSBs. We engineered a novel human iPSC line with a targeted doxycycline-inducible TRF1-FokI fusion protein to acutely induce DSBs at telomeres. Using this model, we demonstrate that TRF1-FokI DSBs activate an ATR-dependent DDR in iPSCs, in contrast to an established ATM-dependent response to telomeric FokI breaks in differentiated cells. ATR activation leads to a potent cell cycle arrest in G2, which we show is p53-independent and can be rescued by treatment with an ATR inhibitor. Telomere lengths are remarkably well-maintained in the face of persistent TRF1-FokI induction. Using CRISPR-Cas9 to cripple the catalytic domain of telomerase, we show that telomerase is largely dispensable for survival and telomere length maintenance following telomeric breaks, which instead appear to be repaired by a mechanism bearing hallmarks of lengthening mediated by homologous recombination, so-called alternative lengthening of telomeres (ALT). Our findings suggest a previously unappreciated role for ALT in telomere maintenance in telomerase-positive iPSCs and reveal distinct iPSC-specific responses to targeted telomeric damage. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.12.02.518927v1?rss=1 Authors: Stout, A. J., Arnett, M. J., Chai, K. M., Guo, T., Liao, L., Mirliani, A. B., Rittenberg, M. L., Shub, M., White, E. C., Yuen, J. S. K., Zhang, X., Kaplan, D. L. Abstract: For cultured meat to succeed at scale, muscle cells from food-relevant species must be expanded in vitro in a rapid and reliable manner to produce millions of metric tons of biomass annually. Toward this goal, genetically immortalized cells offer substantial benefits over primary cells, including rapid growth, escape from cellular senescence, and consistent starting cell populations for production. Here, we develop genetically immortalized bovine satellite cells (iBSCs) via constitutive expression of bovine Telomerase reverse transcriptase (TERT) and Cyclin-dependent kinase 4 (CDK4). These cells achieve over 120 doublings at the time of publication and maintain their capacity for myogenic differentiation. They therefore offer a valuable tool to the field, enabling further research and development to advance cultured meat. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Jennifer Bradley wants you to look and feel good, with a new line of skin care and makeup products made without harmful ingredients and produced with ethical practices. To see these new products in action, visit https://jenniferbradley.com

Kathleen Collins, winner of the 2022 Earl and Thressa Stadtman Distinguished Scientist Award, presented her lecture, "Telomerase holoenzymes" on Monday, April 4, at the 2022 ASBMB Annual Meeting, held in conjunction with Experimental Biology, in Philadelphia. Learn more about her work: https://www.asbmb.org/asbmb-today/people/122121/telomerase-studies-led-collins-to-discoveries.

Dr. Jens Bjørheim is the Chief Medical Officer at Ultimovacs which is taking advantage of the environment for R&D in the science around cancer vaccines in the Oslo region of Norway. Ultimovacs is working with peptide vaccines and long peptides. These peptides will drive for a specific subgroup of immune cells called the CD4 cells, or the helper cells, which coordinate the immune attack against infection and cancer. Jens explains, "In some patients, they do not have the sufficient number or repertoire of immune cells that are needed to kill off the whole tumor. And we believe that adding T-cells or immune cells that can recognize specific things in the tumors, like in our case, an enzyme called telomerase, can benefit the patients in the future. So the checkpoint inhibitors on one side, they allow the immune system to kill off the cancer. On the other side, the immune system sometimes needs more help. There need to be more T-cells and more differentiation among the T-cells to really cure people from cancer." "In our vaccine, we have sequences from an enzyme called telomerase. Why do we target telomerase? Well, in all cancers, they need to have a strategy for eternal cell division, and 85% to 90% of all cancers have turned on this enzyme, telomerase, which allows them, at least in theory, to divide forever. So this is an essential enzyme for the tumor cells. They cannot turn off this enzyme because if they do so, they cannot divide anymore, so we are targeting one of the core and essential features of the cancer." @Ultimovacs #Ultimovacs #Telomerase #Immunotherapy #CD4Cells #CancerVaccine #Cancer #CheckpointInhibitor Ultimovacs.com Download the transcript here

Dr. Jens Bjørheim is the Chief Medical Officer at Ultimovacs which is taking advantage of the environment for R&D in the science around cancer vaccines in the Oslo region of Norway. Ultimovacs is working with peptide vaccines and long peptides. These peptides will drive for a specific subgroup of immune cells called the CD4 cells, or the helper cells, which coordinate the immune attack against infection and cancer. Jens explains, "In some patients, they do not have the sufficient number or repertoire of immune cells that are needed to kill off the whole tumor. And we believe that adding T-cells or immune cells that can recognize specific things in the tumors, like in our case, an enzyme called telomerase, can benefit the patients in the future. So the checkpoint inhibitors on one side, they allow the immune system to kill off the cancer. On the other side, the immune system sometimes needs more help. There need to be more T-cells and more differentiation among the T-cells to really cure people from cancer." "In our vaccine, we have sequences from an enzyme called telomerase. Why do we target telomerase? Well, in all cancers, they need to have a strategy for eternal cell division, and 85% to 90% of all cancers have turned on this enzyme, telomerase, which allows them, at least in theory, to divide forever. So this is an essential enzyme for the tumor cells. They cannot turn off this enzyme because if they do so, they cannot divide anymore, so we are targeting one of the core and essential features of the cancer." @Ultimovacs #Ultimovacs #Telomerase #Immunotherapy #CD4Cells #CancerVaccine #Cancer #CheckpointInhibitor Ultimovacs.com Listen to the podcast here

Astragalus Membranaceus Die Heilpflanze Astragalus Membranaceus ist in der traditionellen chinesischen Medizin (TCM) seit Tausenden von Jahren bekannt, und findet ihren Einsatz als natürliches Heilmittel bei Allergien und Diabetes. Auch als vielfältiges Stärkungsmittel setzen die Chinesen den Astragalus Membranaceus ein. Ursprünglich stammt die Pflanze aus der Mongolei, kam dann über den Norden Chinas in die Volksmedizin der Chinesen, die ihn als Huang Qi als Stärkungsmittel verwenden. Auch die Abwehrkräfte stärkt Astragalus, weshalb gerade bei Epidemien das Präparat vermehrt verwendet wird. Auch hilft Astragalus Membranaceus dabei, die DNA vor krebsverursachenden Mutanten zu schützen, hält uns also in Schuss, verhindert Krankheiten. Das Heilmittel wurde schon von der deutschen Naturheilerin Hildegard von Bingen verwendet, fand seine anfängliche Verwendung in Europa schon vor langer Zeit. Ich persönlich nehme die Heilpflanze Astragalus Membranaceus aber aus anderen Gründen ein. Durch ein Molekül ist die Pflanze in der Lage, die Telomerase zu aktivieren, was Astragalus Membranaceus für das Anti-Aging interessant macht, das Altern des Körpers also bremsen kann. Mir geht es nicht darum, dass ich Hundert Jahre alt werde, sondern ich möchte meine Gesundheit erhalten, solange es geht, weshalb ich viel Zeit und eigene Forschung in die Erprobung und Verwendung der Nahrungsergänzungsmittel stecke von denen ich glaube, dass sie bei der Verwirklichung meiner Ziele hilfreich sein könnten. Wie Körperzellen altern ist bekannt, ihre Teilung hört nach ca. 50 mal auf, eine Erneuerung ist dann nicht mehr möglich, die Zeit ist abgelaufen. Sie sterben, wir sterben sozusagen auf Raten, wenn unsere biologische Uhr zu ihrem Ende kommt. Von verschiedenen Wissenschaftlern werden die Telomere als diese innere Uhr angesehen, die mit Astragalus Membranaceus die einige Lebenszeit verlängern helfen. Die gute Wirkung auf den Blutzucker- und Cholesterinspiegel (durch die durch das Heilmittel verminderte Cholesterinaufnahme im Darm) machen Astragalus Membranaceus für mich zu einem meiner persönlichen Superfoods, das ich täglich einnehme. Auch enthält das Naturheilmittel wichtige Aminosäuren, Fettsäuren und Mineralstoffe, die unserem Körper dabei helfen, fit und gesund zu bleiben. Seit ich dieses Superfood einnehme ist meine Haut deutlich besser geworden, Falten werden geglättet (trotz meiner fast 60 Lebensjahre habe ich keine einzige Falte, vielleicht deshalb), das Bindegewebe erscheint vital und gestrafft. Nach den Vorstellungen der traditionellen chinesischen Medizin TCM stärkt Astragalus Membranaceus das Qi, die von den Chinesen so verehrte Lebenskraft (etwa auch durch Qi Gong, das ich auch täglich trainiere). Auch deshalb habe ich dieses Superfood in mein Programm aufgenommen, ich fühle mich durch die regelmässige Einnahme deutlich gestärkt. Der Weg ist das Ziel! hier lesen Sie Teil 1 der Serie "meine Superfoods" click Jeder Mensch ist der Urheber seiner eigenen Gesundheit oder Krankheit - Buddha - Ehrenname des Siddharta Gautama - 560 bis 480 vor dem Jahr Null Copyright: https://shaolin-rainer.de Bitte laden Sie sich auch meine App "Buddha-Blog" aus den Stores von Apple und Android.

Episode 15: Liz Parrish is the CEO of BioViva, a company whose goal is to genetically modify humans so that the body continuously stays in a state of homeostasis, as well as a graduate from Buckinghamshire University for her International MBA. In this episode, she provides insight on the work BIoViva is doing, various gene therapies, her acts as a pioneer, statins, telomerase, the benefits and deficits of medical tourism, and present and future technologies that can help extend life.

Episode 689: Telomerase

Episode 689: Telomerase

It was a privilege to meet Professor George Birkmayer back in 2010 at the Dubai Congress of Anti-Aging Medicine. I was so thrilled to attend his lecture about “the secret of our life energy: NADH” who presented me with his book “NADH: The Biological Hydrogen – The Secret of Our Life Energy” Professor George Birkmayer, M.D., Ph.D., is the developer of stabilized NADH, and the discoverer of the therapeutic effect of NADH, also known as Coenzyme-1, which exhibits  energizing effects for all bodily functions and organs. He is a world-renowned biochemical researcher and was the Medical Director of the Birkmayer Institute for Parkinson's Therapy, which has treated thousands of patients suffering from Parkinson's disease after having studied the biochemical connections between Parkinson and NADH . The more NADH a cell has available, the more energy it can produce, the better it functions and the longer the cell (and the entire organism) lives. Though NADH is present in our foods, we take in only marginal amounts of it from our daily diet. Most of the NADH is destroyed during the cooking process. The situation would not be greatly improved even if our diet consisted mostly of raw meat and fish, as the NADH present in these foods is degraded within seconds by the acid environment produced by the gastric juices in the stomach. Highlights of our conversation: 1. Biological Functions of NADH. 2. How it was created as a tablet form to be bioavailable on the human organism. 3. Health benefits of NADH. 4. NADH is also used for improving athletic endurance and treating chronic fatigue syndrome (CFS). NADH Rapid, formulated by Professor Birkmayer how rapidly it can enhance energy levels. 5. How long a person can maintain heightened energy levels after taking NADH Rapid? 6. How does it affect sleep? The regulation of Circadian Rhythm. 7. Who can take NADH? How long can someone take it? 8. NADH can interact with Telomerase enzyme in order to stop, slow or reverse the telomere shortening that happens as we age. 9. Maintenance of a healthy weight with NADH Kilow.

Schlechte Ernährung, Alkohol und Rauchen, viel Stress und wenig Sport – Daniela lebt alles andere als gesund und macht sich kaum Gedanken über das Altwerden. Bis jetzt. Kann die Wissenschaft ihr helfen, jung zu bleiben?

What can our collective telomeres tell us about our lives, our health and our longevity? We’ll back up a step, and talk about what they are and the fascinating role they play in our wellbeing. We hit on lots more topics – including purpose, perseverating, and conscientiousness. Let’s walk and connect!   LET’S TALK THE WALK! Wellness While Walking Facebook page Wellness While Walking on Instagram Wellness While Walking on Twitter Wellness While Walking website for show notes and other information Coach Carolyn on Clubhouse: @stepstowellness wellnesswhilewalking@gmail.com   RESOURCES AND SOURCES (some links may be affiliate links)   Telomeres and Healthy Aging The Telomere Effect, Dr. Elizabeth Blackburn and Dr. Elissa Epel How to Find Purpose and Better Sleep, fridaymagazine.ae Study of Astronaut Twins Hints at Spaceflight Health Effects, nationalgeographic.com At Home Telomere Testing Is Not a Reliable Marker of Aging, Researcher Says, sciencenews.org   DISCLAIMER Neither I nor most of my podcast guests are doctors or healthcare professionals of any kind, and nothing on this podcast or associated content should be considered medical advice. The information provided by Wellness While Walking Podcast and associated material, by Whole Life Workshop and by Bermuda Road Wellness LLC is for informational and entertainment purposes only. It is not intended to be a substitute for professional medical advice, diagnosis or treatment. Always seek the advice of your physician or other qualified health care provider with any questions you may have regarding a medical condition or treatment, and before undertaking a new health care regimen, including walking.     Thanks for listening to Wellness While Walking, a walking podcast.  

Colleagues, if you’ve been following me for any time, you’ve heard me speak frequently about aging as the top driver of chronic disease. In today’s interview, I dive into evidence-based integrative protocols to slow down and reverse the aging process. My guest, Dr. Joseph Cleaver MD, is a Fellow of the American Board of Anti-aging and Regenerative Medicine, is board-certified in internal medicine, a rheumatologist, on faculty at A4M and MMI and has authored and published a wealth of research and scholarly articles. He founded Paradigm Wellness Medical Group in Dallas and Sonoma Valley, California, AND he is Medical Director at Boutique Wellness in Winston, North Carolina. Folks, you’ll want to be ready to take notes during this interview, as Dr. Cleaver shares his personalized senolytic protocols specific to patient phenotypes. Listen, share, and leave a starred rating, if you wouldn't mind! Thanks for listening. ~DrKF

Jung, frisch und fit bleiben bis ins hohe Alter. Davon träumt wohl jeder. Dieser Traum rückt nach neuesten Studien ein ganzes Stück weit näher. In unserem Körper gibt es nämlich ein bestimmtes Enzym (Telomerase), dass die Chromosomen auch im reiferen Alter noch einmal wachsen lässt. Klingt erst mal kompliziert, ist aber ganz simpel, wie Du in dieser Folge lernen wirst. Durch die richtige Ernährung können wir das "Jungbrunnen-Enzym" aktivieren. Neugierig geworden? Dann höre jetzt unsere neue Folge!

Imagine a time in the not to distant future when Alzheimer's no longer exists. The search for the fountain of youth has largely been a work of science fiction. But science is on the cusp of a revolutionary breakthrough. Dr. Michael Fossel is a physician and an expert in the science of cell aging and human aging. WSIU's Jeff Williams recently talked with Dr. Fossel about his book The Telomerase Revolution for this edition of In The Author's Voice.

Join Dr. Dan as he welcomes William Andrews, PhD, the worlds leading researcher and expert on telomeres. He is the CEO of Sierra Science, a company that is dedicated to curing aging. He is also featured in the critically acclaimed documentary: The Immortalists. Topics discussed: What are telomers and telomerase? How do we test our levels? What can we do to optimize our telomeres? What supplements support this process?

Stephen Euin Cobb is today's featured speaker. Topic: A full explanation of the final results of my "TA-65 Evaluation Project" which I started nearly a year ago. In this episode I describe in detail the immunology blood test results for my mother and myself which were taken at the end of the evaluation period, and compare them with the immunology blood test results taken at the start the evaluation period. To bring everyone up to speed on my TA-65 evaluation project, I provide a thorough summary of the project itself. And I explain the miscellaneous benefits I and my mother have observed. These benefits include changes in: arthritis pain, frequency and vividness of dreams, as well as fingernail thickness and growth rate. TA-65 has been shown in clinical trials to successfully lengthen telomeres, which are fundamental to the health of cells. TA-65 is produced only by TASciences, Inc. Hosted by Stephen Euin Cobb, this is the July 18, 2012 episode of The Future And You. [Running time: 40 minutes] Stephen Euin Cobb is an author, futurist, magazine writer and host of the award-winning podcast The Future And You. A contributing editor for Space and Time Magazine; he is also a regular contributor for Robot, H+, Grim Couture and Port Iris magazines; and he spent three years as a columnist and contributing editor for Jim Baen's Universe Magazine. He is an artist, essayist, game designer, transhumanist, and is on the Advisory Board of The Lifeboat Foundation. His novels include Bones Burnt Black, Plague at Redhook and Skinbrain. Announcement: For a limited time, one of my novels is on sale. The Kindle edition of Skinbrain (Cerebrodermus Fantastica), my most recent and most futuristic novel, has been reduced to just $2.99. That's right, under three bucks for what I consider my best novel.

Stephen Euin Cobb (your host) gives his opinion on a variety of future topics. Topics: how popular science fiction movies effect decision making within our civilization; immortality through nanotechnology; movies such as: Blade Runner, Terminator, Minority Report, and Gattica; virtual realities (such as Second Life and World of Warcraft); why human augmentation may be inevitable; the widespread resistance to human augmentation which exists already; the creation of human organs using 3D printers which print with living cells; the de Vinchi surgical machine; the novel Rollback (by Robert J. Sawyer); Life Extension and Age Reversing; measurable loss of function in the various organs of the body; the likely availability of life extension technologies, and the effect they may have on the future of civilization. This is the November 16, 2011 episode of The Future And You. [Running time: 42 minutes]. This interview of Stephen Euin Cobb was recorded using Skype on October 15, 2011, and was conducted by Richard Buxton (a screenwriter and film student in London) as part of Richard's research for his thesis, which concerns the cumulative effect science fiction movies have on civilization. Richard Buxton studied Fine Art at Central St Martins in London, and completed an MA in Production Design for Film & TV at Kingston University. Currently he is working toward a Film Making Degree at SAE Institute London with an emphasis in screenwriting. Part of that work will be his thesis which concerns the effect which science fiction films have had on society. He writes for Tracksounds (a website dedicated to film scores) and has appeared on SoundCast (a podcast of interviews and commentary about film scores). Stephen Euin Cobb is an author, futurist, magazine writer and host of the award-winning podcast The Future And You. He is also a artist, essayist, game designer, transhumanist, and is on the Advisory Board of the Lifeboat Foundation. Three years a columnist and contributing editor for Jim Baen's Universe Magazine, he has also become a regular contributor at Robot Magazine, H+ Magazine, Space and Time Magazine: and has written for Digit, Grim Couture and Port Iris magazines. His novels include: Bones Burnt Black, Plague at Redhook and Skinbrain.  News Item: CBS News reports that Ridding body of old "zombie" cells slows aging process, study shows. Mayo Clinic scientists may have hit upon a way to slow the aging process. The key, they report in a tantalizing new study, is purging the body of senescent cells - old "zombie" cells that no longer work as they should.

Richard Buxton (a screenwriter and film student in London) is our featured guest. Topic: Trends in movies and the movie making industry. Richard Buxton studied Fine Art at Central St Martins in London, and completed an MA in Production Design for Film & TV at Kingston University. Currently he is working toward a Film Making Degree at SAE Institute London with an emphasis in screenwriting. Part of that work will be his thesis which concerns the effect which science fiction films have had on society. He writes for Tracksounds (a website dedicated to film scores) and has appeared on Soundcast (a podcast of interviews and commentary about film scores). Hosted by Stephen Euin Cobb, this is the November 9, 2011 episode of The Future And You. [Running time: 28 minutes]. This is the second half of an interview recorded using Skype on October 15, 2011.   News Items: [1] DARPA plans to put 1,000 3-D printers (rapid fabrication devices) into high schools across the United States as a way to encourage American young people to go into engineering and particularly manufacturing, and to help high schoolers build STEM skills. [2] A Georgia Tech team has received a $3 million grant to explore how bacteria interact on a molecular level to form networks. The research may one day guide the design of nanodevices able to communicate with one another and accomplish tasks at the nanolevel of one billionth of a meter in size, which could lead to future breakthroughs in nanorobotics. [3] Military personal, academics, and diplomats met in Virginia October 25-28 for Unified Quest, a seminar war game to explore the geostrategic environment of the future. “The purpose of this symposium is about plausible strategic landscapes,” said Col. Kevin Felix, director of the Army's Future Warfare Division. “The four working groups were given wide latitude to work towards 2028, and it was about bringing in the right folks.”