Podcasts about Longo

In this episode, you'll learn: How Dr. Melissa Longo discovered chiropractic and why it changed her life Why there isn't just one “right” way to build a successful chiropractic practice The story behind Melissa's transition to a streamlined home-based practice model How simplifying your practice can increase freedom, profitability, and flexibility Why understanding your values and lifestyle goals is critical to designing your practice How chiropractors can reduce stress by eliminating unnecessary complexity The importance of building systems that support the life you want outside the practice How coaching and mentorship can help chiropractors rethink their business models Why success should be defined on your own terms—not someone else's Key Takeaway The most successful chiropractors aren't necessarily those who build the biggest practices—they're the ones who build practices that align with their values, lifestyle, and purpose. Resources Mentioned Learn more about Dr. Melissa Longo:https://drmelissalongo.com Listen to Dr. Longo's podcast:Rockstar Doctor Life Subscribe & Connect If you enjoyed this episode, be sure to subscribe to The Successful Chiro Podcast for more conversations designed to help chiropractors grow better practices and better lives.

Defesa Civil - Boletim Previsão do Tempo para 11/03

Host Carter Yates and senior writer Mike Craven break down all things Texas CFB. (INTRO – 5:45) Craven is in a social media bunker after rating Texas State's Brad Jackson ahead of Marcel Reed (5:45 – 21:45) Why Texas Tech is NOT a national title contender in 2026 (21:45 – 36:00) Who is the best in 2026? TCU, Houston or SMU? (36:00 – END) Phil Longo and Scott Abell year one grades Learn more about your ad choices. Visit megaphone.fm/adchoices

We are pleased to welcome Dr Valter Longo to this episode of Living Well with MS. Dr Longo is the scientist behind the Fasting Mimicking Diet. He is a bio-gerontologist and cell biologist serves as a professor at the USC Davis School of Gerontology and as the director of the USC Longevity Institute. He is the creator of the fasting-mimicking diet, a program that claims to mimic the effects of periodic fasting. To read Dr Longo's full bio, click here.  Originally broadcast in 2020, this episode has been edited to remove out-of-date content and reuploaded in 2026 to ensure it remains relevant and useful. 02:08 Today's rising fascination with fasting diets  03:50 Main differences between the fasting-mimicking diet and other fasting diets  05:03 Diving into blue zones, where a higher percentage of the population lives to 100  06:55 The correlation between the centenarians and people who are fasting   11:04 Does fast mimicking help people with MS live better and longer?  14:03 The different types of fast-mimicking diets including 5:2, 16:8 and occasional water fasting  24:54 What should we eat between fasts?  29:28 What is the ProLon diet, and for those on a budget, how can peopel get some of the benefits on their own? 

We found a cheat code for learning Spanish using Claude and Anki (without studying grammar). Plus, the Cult Brand marketing framework that turns customers into superfans.In this episode, Andrew reveals why he is moving to Mexico City and going all in on his startup. Sean breaks down how he scaled his agency to 18 employees and the specific Positioning Strategy he uses to charge premium prices.Links:Andrew's Twitter: @AndrewAskinsAndrew's website: https://www.andrewaskins.com/MetaMonster: https://metamonster.ai/Slackletter: https://slackletter.com/Sean's Twitter: @seanqsunMiscreants: http://miscreants.com/Margins: http://margins.so/Sean's website: https://seanqsun.com/For more information about the podcast, check out https://www.smalleffortspod.com/Transcript:00:00:00,000 --> 00:00:05,200I've had several situations where I just like make stupid mistakes. I feel very envious of the00:00:05,200 --> 00:00:10,800ability to like, spend all your time and energy on like one thing, we kind of made a mistake that I00:00:10,800 --> 00:00:15,200think I've seen a lot of people make. Ever felt like you're stuck making the same mistakes or on00:00:15,200 --> 00:00:20,480the verge of something big but held back? Today we explore founder struggles, mistakes, burnout, and00:00:20,480 --> 00:00:25,239focusing on real growth. We'll discuss creating content for people, not algorithms, and staying00:00:25,240 --> 00:00:29,640grounded in what matters. I'm Andrew Askins, founder of meta monster, and I'm Sean's son00:00:29,640 --> 00:00:34,000founder of miscreants. Let's dive into the journey. Like I think a lot of founders like, identify that800:00:34,000 --> 00:00:38,559by accident and build a product around that. I don't give it. AI thinks I'm stupid. AI already900:00:38,560 --> 00:00:43,199knows I'm stupid. You are selling a methodology where your solution is the only product that1000:00:43,200 --> 00:00:47,240actually fits said methodology. Learning a language is a lot of work. Demand is a fluid1100:00:47,240 --> 00:00:52,600substance. My biggest thing is like social anxiety of picking up and making mistakes. Every small1200:00:52,600 --> 00:00:54,400move is how we can.1300:00:59,970 --> 00:01:06,489How's your Spanish going? Pretend I was in Spanish. Um.1400:01:07,050 --> 00:01:13,769Not something smart. So menos lento is is muy, uh. Muy Modesto.1500:01:13,809 --> 00:01:20,729Muy, muy Modesto. Um, I, uh, I have been texting a lot in Spanish lately, so, like, my1600:01:20,730 --> 00:01:27,449reading and writing has been getting a lot better. Faster than my speaking and listening. Um,1700:01:27,449 --> 00:01:33,009I still, I was just hanging out with a bunch of friends last night. Um, and to be fair, uh, four of1800:01:33,010 --> 00:01:39,650my friends, um, were were ganging up on one of their boyfriends. And so it was,1900:01:39,809 --> 00:01:46,689uh, there was a lot of very rapid Spanish, um, and a lot of, like, g. Longo slang flying around, so,2000:01:46,730 --> 00:01:51,089like, not the easiest to understand, but I was just, like, I was just sitting back laughing, like, I2100:01:51,089 --> 00:01:55,929don't understand any of this. Although, interestingly enough, understood everything at the2200:01:55,929 --> 00:02:02,830same time. You know, like the universal language. It was pretty obvious what was happening. Nice.2300:02:03,550 --> 00:02:10,470Also, I heard you have a new, uh, nickname in Mexico City. Yeah, we don't need to go into that.2400:02:10,470 --> 00:02:17,270That's fine. I feel like. Yeah. Okay. All right. Fine. Am I? My friends, Rosa and Wyatt. Uh,2500:02:17,270 --> 00:02:23,710Rosa's from here. Um. Uh, and, uh, she's dating my my good friend Wyatt. Um,2600:02:23,750 --> 00:02:30,629and one night, I may have had a little too much fun, and, uh, they had to take care of me a bit,2700:02:30,630 --> 00:02:37,630and I got got dubbed El Polito clause. Um, which means, uh, the little colored chick.2800:02:37,830 --> 00:02:44,589Um, the the backstory is in Mexico City. Like, I don't know, 10 or 20 years2900:02:44,589 --> 00:02:49,550ago. Uh, there used to be markets everywhere where you could get these little baby chicks that had3000:02:49,550 --> 00:02:55,710been dyed like neon colors. And the dye was very bad for the chicks. And so, um, you would, like, buy3100:02:55,710 --> 00:03:01,319them for your kid, and they would inevitably die within two weeks. Um, and so they were like, just3200:03:01,320 --> 00:03:08,240very hard to keep alive. And so, Polito declares, is a, uh, is a joke you3300:03:08,240 --> 00:03:14,720make about someone when they can't take care of themselves, when they when they need, need help. You3400:03:14,720 --> 00:03:20,319know, I don't think you told me. Did I not give you the context? No, that was way more morbid than I3500:03:20,320 --> 00:03:27,320thought. I thought it was just like. Like it meant, like ugly duckling or like. I mean, it kind of does.3600:03:27,320 --> 00:03:33,640It has a morbid start, but it basically just means, like, are you dumb little thing you need, like,3700:03:34,440 --> 00:03:40,839we got you. It's okay. Um,3800:03:41,600 --> 00:03:48,159sorry. I'm just. I'm trying to imagine I got it all in neon, baby chick. Oh.3900:03:49,240 --> 00:03:56,179Um. Oh, that's. Did you find them? Yeah, yeah, yeah, yeah, they're kind of like peeps, you know? they're4000:03:56,179 --> 00:04:02,979like poop colored. Yeah, but, like living beings. Yeah. So very, very. Oh, wow. Okay. They4100:04:02,979 --> 00:04:09,899got. All right. Next topic. Um. One thing I've been doing, though, that's been fun. Um,4200:04:10,099 --> 00:04:15,499so to try to work on my Spanish, I there's this app that all the, like, language learning nerds use4300:04:15,500 --> 00:04:22,499called Anki. Um, it's a spaced repetition flashcard app. So basically you practice words and then like4400:04:22,499 --> 00:04:26,858when you get them right, it's depending on how easy or hard it was. It'll like space out how4500:04:26,859 --> 00:04:30,859often it shows it to you. So like as you learn words you see them less often. The new words4600:04:30,859 --> 00:04:36,699you're struggling with. You see them more often. Um, and so I've been wanting to use Anki for a really4700:04:36,700 --> 00:04:41,379long time. Um, but like, their interface is atrocious. It's a great app. It's all open source,4800:04:41,379 --> 00:04:46,339but it's like the most painful thing to enter stuff. And they have this, like, incredible4900:04:46,339 --> 00:04:53,299community of, um, of like people who publish free decks of words. But every deck I found, I5000:04:53,299 --> 00:04:59,309was just like, I like this isn't what I want to learn. Like, this isn't helpful. Um, and so I've been5100:04:59,310 --> 00:05:04,789wanting to create my own deck for a long time, and I was like, kind of like, maybe I'll just vibe code5200:05:04,790 --> 00:05:08,789something....

Confira nosso podcast inovador, gerado por Inteligência Artificial! Os episódios são criados a partir dos artigos do site Giro Financeiro, trazendo informações valiosas diretamente para você.Artigo: Educação Financeira para Funcionários: Benefícios a Longo PrazoO podcast aborda a educação financeira no trabalho como uma ferramenta estratégica para promover o bem-estar dos colaboradores e o sucesso das empresas. Ao oferecer programas que ensinam sobre orçamento pessoal, investimentos e fundos de reserva, as organizações conseguem reduzir o estresse financeiro e aumentar a produtividade e retenção de talentos.Acesse o nosso artigo em texto: https://tinyurl.com/4mfmy4unCÓDIGOS DE INDICAÇÃO CARTÃO DE CRÉDITOhttps://bit.ly/3RuEZ21GRUPO GRATUITO NO WHATSAPPhttps://tinyurl.com/5n79dtkmLivros sobre Educação Financeira https://amzn.to/47uuEY2Nosso site https://girofinanceiro.com.br/Canal do Youtube https://tinyurl.com/43jux7mr

Faça Amigos ao Longo da Jornada - Luis Felipe (Pipe) by Chácara Primavera

Faça Amigos ao Longo da Jornada - Mike Goheen by Chácara Primavera

Esse conteúdo é uma parceria entre RW Cast e RFI.

Giacomo Orlando “Chi è il mio prossimo? Quando l'amore diventa scomodo” Luca 10: 25-29 Maurizio Longo “Dare quando sembra di non avere” 1 Re 17: 12-15 1 Re 17: 12 1 Re 17: 15 1 Re 17: 12 2 Re 4: 2 Matteo 15 :34-37 Biagio Narducci “Io non sono degno” Luca 7: 1-10 Geani Daragiu “Custodisci il tuo Eden” Genesi 2: 15 Proverbi 4 :23 1 Timoteo 4 :14 Isaia 58: 11 --Guarda Canale 245 | Tivùsat 454 | Sky 854Scopri di più su www.paroledivita.org/linkinbio

No FIRE e na construção de portefólio, não há uma receita certa: nem entre pessoas, nem para a mesma pessoa ao longo dos anos. Links úteis Artigo: Vendi alguns ETF Artigo: Porque escolhi investir apenas no VWCE Pontos de venda do livro: FIRE com obrigações ⁠⁠⁠⁠⁠⁠⁠⁠Todos os pontos de venda do livro⁠⁠⁠⁠⁠⁠⁠⁠ "Conquista a tua liberdade financeira" Novas partilhas em ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠@damadeouros.pt⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠www.damadeouros.com⁠⁠ Learn more about your ad choices. Visit megaphone.fm/adchoices

The episode explains how pole dancers can get stronger using progressive overload, defined as gradually increasing training stress so the body adapts during rest and the same demands become easier over time. It outlines adaptation timelines: neurological and cardiovascular changes can occur quickly (sometimes within a session for neuro drills), noticeable strength gains typically appear after about 3–6 weeks, connective tissue (tendons/ligaments) adapts around the 3-month mark, and bone density changes occur closer to 6 months. Rosy emphasizes easing back into training—especially after a break or postpartum—avoiding self-punishment, and prioritizing rest because adaptation happens during recovery. It describes ways to increase load for pole and bodyweight training: increase training frequency while keeping at least 1–2 rest days per week, increase repetitions, use time-based conditioning like a “pole treadmill” (repeated climbs/descents for time), increase resistance via weights/bands or by selecting harder bodyweight progressions, and use isometrics by holding longer or increasing tension. It notes that muscle damage is not necessarily required for positive adaptation and references Felipe Damas' work (primarily in hypertrophy research), while clarifying the focus is strength training rather than bodybuilding. The episode also explains that the body responds to chronic life stress similarly to training stress, which can hinder strength gains, and encourages stress reduction and enjoyable movement.Citations:SELYE H. (1950). Stress and the general adaptation syndrome. British medical journal, 1(4667), 1383–1392. https://doi.org/10.1136/bmj.1.4667.1383Monti, E., Franchi, M. V., Badiali, F., Quinlan, J. I., Longo, S., & Narici, M. V. (2020). The Time-Course of Changes in Muscle Mass, Architecture and Power During 6 Weeks of Plyometric Training. Frontiers in physiology, 11, 946. https://doi.org/10.3389/fphys.2020.00946Damas, F., Phillips, S. M., Vechin, F. C., & Ugrinowitsch, C. (2015). A review of resistance training-induced changes in skeletal muscle protein synthesis and their contribution to hypertrophy. Sports Medicine, 45(6), 801–807.Damas F, Phillips SM, Libardi CA, Vechin FC, Lixandrão ME, Jannig PR, et al. (September 2016). "Resistance training-induced changes in integrated myofibrillar protein synthesis are related to hypertrophy only after attenuation of muscle damage". The Journal of Physiology. 594 (18): 5209–22. doi:10.1113/JP272472. PMC 5023708. PMID 27219125Ahola, R., Korpelainen, R., Vainionpää, A., Leppäluoto, J., & Jämsä, T. (2009). Time-course of exercise and its association with 12-month bone changes. BMC musculoskeletal disorders, 10, 138. https://doi.org/10.1186/1471-2474-10-138Plotkin, D., Coleman, M., Van Every, D., Maldonado, J., Oberlin, D., Israetel, M., Feather, J., Alto, A., Vigotsky, A. D., & Schoenfeld, B. J. (2022). Progressive overload without progressing load? The effects of load or repetition progression on muscular adaptations. PeerJ, 10, e14142. https://doi.org/10.7717/peerj.14142Chapters:00:00 Get Stronger for Pole: What We're Covering Today00:55 Membership Shout-Out + How My Training Programs Work02:24 Progressive Overload 101 (Stress → Rest → Adapt)03:50 Adaptation Timelines: Nervous System, Cardio, Strength05:53 Long-Game Gains: Tendons, Ligaments & Bone Density06:59 Coming Back to Pole: Patience, Rest, and Consistency08:01 How to Add Load in Pole Training (Frequency, Reps, Resistance)11:12 Isometrics & Bodyweight Progressions (Making Moves Harder)14:48 Wrap-Up: Stress Management, Keep Showing Up

Nouveaux pilotes, un brin déjantés, à bord de la Libre Antenne sur RMC ! Jean-Christophe Drouet et Julien Cazarre prennent le relais. Après les grands matchs, quand la lumière reste allumée pour les vrais passionnés, place à la Libre Antenne : un espace à part, entre passion, humour et dérision, débats enflammés, franc-parler et second degré. Un rendez-vous nocturne à la Cazarre, où l'on parle foot bien sûr, mais aussi mauvaise foi, vannes, imitations et grands moments de radio imprévisibles !

A projeção de queda está estimada em 23%, com o greening aumentando a severidade da situação

Entidade de produtores faz manifesto sobre a situação do setor e reforça que pecuaristas de leite já trabalham com prejuízo

Global City Church is a missions initiative that contains a fellowship of local churches that empower global leaders to advance the gospel. Instead of missionaries coming to us for help, we are going to help the missionaries! In this video, hear from 3 gospel-advancing men on how to be a gospel-advancing church. Find out more at https://kenosha.church/globalcitychurch

No quadro PECUÁRIA LEITEIRA , nono mês seguido que queda nos preços do leite pagos ao produtor; No HORA DO HARAS , o encontro dos criadores de Quarto de Milha que vai acontecer em Campinas-SP

STOP intermittent fasting if you think it automatically keeps you young. In this episode, you'll learn why short-term fasting results can mislead long-term aging outcomes, and how duration, frequency, refeeding, and protein intake determine whether fasting supports longevity or quietly accelerates decline. Watch this episode on YouTube for the full video experience: https://www.youtube.com/@DaveAspreyBPR Host Dave Asprey sits down with Valter Longo, one of the world's leading longevity researchers with over 30 years of experience studying aging, nutrition, and disease prevention. Dr. Longo is the Director of the Longevity Institute at the University of Southern California's Leonard Davis School of Gerontology and the Director of the Longevity and Cancer Program at IFOM, the Italian Foundation for Cancer Research Institute of Molecular Oncology in Milan. He is the author of the bestselling book The Longevity Diet and was named one of TIME Magazine's 50 most influential people in health care for his research on fasting-mimicking diets. Together, Dave Asprey and Dr. Longo explain why many people focus too heavily on short-term effects and extrapolate them incorrectly across a lifetime. They break down how intermittent fasting differs biologically from multi-day fasting, why five-day fasting cycles trigger deeper cellular changes, and how insulin, IGF-1, mTOR, and growth hormone shape aging, regeneration, and disease risk over time. The conversation covers protein and amino acid intake, muscle preservation, frailty risk, and the tradeoffs between strength, function, and longevity. They explore ketosis, fasting-mimicking diets, stem cell activation, mitochondrial function, neuroplasticity, and why equilibrium and cycling matter more than constant restriction. Dave and Valter also discuss supplements, nootropics, creatine, carnivore-style eating, metabolism, sleep optimization, and how AI may eventually personalize fasting and nutrition based on individual biology rather than population averages. You'll learn: • Why short-term fasting benefits do not predict long-term longevity • How fasting duration changes gene expression and cellular regeneration • The difference between intermittent fasting and multi-day fasting • How protein and amino acids influence mTOR, IGF-1, and aging • Why muscle, strength, and longevity must be balanced, not maximized • When ketosis overlaps with fasting and when it does not • Why supplements can disrupt biological equilibrium • How AI could support future personalization in fasting and nutrition Dave Asprey is a four time New York Times bestselling author, founder of Bulletproof Coffee, and the father of biohacking. With over 1,000 interviews and 1 million monthly listeners, The Human Upgrade is the top podcast for people who want to take control of their biology, extend their longevity, and optimize every system in the body and mind. Each episode features cutting edge insights in health, performance, neuroscience, supplements, nutrition, hacking, emotional intelligence, and conscious living. Thank you to our sponsors! • BEYOND Conference 2026 | Register now with code DAVE300 for $300 off at https://beyondconference.com/• AquaTru | Go to https://aquatruwater.com/daveasprey and save $100 on all AquaTru water purifiers.• Caldera + Lab | A small habit with big results. Go to https://CalderaLab.com/DAVE and use code DAVE for 20% off your first order.• Timeline | Go to https://timeline.com/Dave for 20% off.Dave Asprey is a four-time New York Times bestselling author, founder of Bulletproof Coffee, and the father of biohacking. With over 1,000 interviews and 1 million monthly listeners, The Human Upgrade brings you the knowledge to take control of your biology, extend your longevity, and optimize every system in your body and mind. Each episode delivers cutting-edge insights in health, performance, neuroscience, supplements, nutrition, biohacking, emotional intelligence, and conscious living. New episodes are released every Tuesday, Thursday, Friday, and Sunday (BONUS). Dave asks the questions no one else will and gives you real tools to become stronger, smarter, and more resilient. Keywords: intermittent fasting longevity, fasting mimicking diet, fasting and aging science, biohacking fasting podcast, longevity fasting research, protein restriction longevity, amino acids aging, mTOR IGF-1 longevity, mitochondria aging science, neuroplasticity fasting, ketosis fasting science, metabolism longevity podcast, anti-aging fasting, functional medicine longevity, supplements fasting debate, nootropics brain optimization, muscle frailty aging, sleep optimization longevity, AI personalized nutrition, carnivore diet longevity debate, Dave Asprey fasting, Valter Longo longevity, longevity diet podcast, human performance aging Resources: • Learn More About Valter's Work At: https://valterlongo.com/ • Join My Fasting Challenge: https://daveasprey.com/#14-day • Get My 2026 Biohacking Trends Report: https://daveasprey.com/2026-biohacking-trends-report/ • Join My Low-Oxalate 30-Day Challenge: https://daveasprey.com/2026-low-ox-reset/ • Dave Asprey's Latest News | Go to https://daveasprey.com/ to join Inside Track today. • Danger Coffee: https://dangercoffee.com/discount/dave15 • My Daily Supplements: SuppGrade Labs (15% Off) • Favorite Blue Light Blocking Glasses: TrueDark (15% Off) • Dave Asprey's BEYOND Conference: https://beyondconference.com • Dave Asprey's New Book – Heavily Meditated: https://daveasprey.com/heavily-meditated • Upgrade Collective: https://www.ourupgradecollective.com • Upgrade Labs: https://upgradelabs.com Timestamps: 0:00 Introduction & Aging Fundamentals 4:36 Fasting Mimicking Diet Overview 7:03 Insulin, IGF-1 & mTOR 11:03 Body Fat & Fasting Frequency 17:08 The Protein Debate 20:22 Blue Zones & Centenarian Evidence 23:10 Amino Acids & Leucine 30:30 Growth Hormone & Longevity 34:01 Five-Day Fasting Benefits 40:55 Personalization & AI 42:29 Plant-Based Concerns 49:07 Fasting Risks & Limits 53:05 Supplements & Equilibrium 1:03:05 Ranking Longevity Pathways 1:05:05 Modern Environmental Challenges 1:16:21 Final Thoughts See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

Phil Longo, head football coach at Sam Houston State, joins the show to share why Drake Maye always stood out as a quarterback and competitor. From recruiting him out of high school to coaching him at North Carolina, Longo explains Maye's athleticism, intelligence, and relentless competitiveness, along with what separates great quarterbacks from the rest and how those traits show up on the biggest stage. #nfl #newengland #patriots #newenglandpatriots #superbowl #drakemaye Learn more about your ad choices. Visit megaphone.fm/adchoices

Arthur Grynbaum revisita sua trajetória no Grupo Boticário, cinco anos após sua primeira entrevista para o podcast. Em um novo bate-papo com Mariana Amaro, em mais um episódio Do Zero ao Topo, ele fala da aceleração digital no pós-pandemia à transição de CEO para o conselho, além de revelar decisões difíceis, crescimento global e os dilemas de liderar no curto prazo sem perder o futuro de vista.

No quadro PROTEÍNAS ANIMAIS a suinocultura no RS incia o ano com ritmo mais lento e leve pressão nos preços, mas cenário é positivo

A bold reimagining of life that bridges science, philosophy, cybernetics, and the complexities of biological existence The Organism Is a Theory: Giuseppe Longo on Biology, Mathematics, and AI (Giuseppe Longo and Adam Nocek, 2026) is an intriguing synthesis of decades of interdisciplinary research by eminent mathematician and biological scientist Giuseppe Longo. A unique collaboration between Longo and philosopher of technology Adam Nocek, the volume confronts foundational issues in the history of mathematics, computer science, physics, and theoretical biology. Challenging conventional approaches that apply computational and formalist models to the biological world, Longo reveals how the limitations of these models hinder the understanding of organismic complexity, development, and evolution. Through a critique of dominant scientific paradigms, he emphasizes the need for a new biological theory that accounts for the temporal and spatial intricacies of life. Enhanced by Nocek's comprehensive introduction and a fascinating three-part interview with Longo, The Organism Is a Theory offers a bold rethinking of the biosciences, integrating the work of Alan Turing, Bernhard Riemann, Henri Poincaré, Kurt Gödel, and others into Longo's vision of critical biology. Bridging scientific and philosophical discourses, this book creatively applies insights from mathematics, physics, and computing into the study of the organism to present a new theoretical approach to understanding biological complexity that resists reductive mechanistic and informatic explanations. Retail e-book files for this title are screen-reader friendly with image accompanied by short alt text and/or extended description. Learn more about your ad choices. Visit megaphone.fm/adchoices Support our show by becoming a premium member! https://newbooksnetwork.supportingcast.fm/science-technology-and-society

A bold reimagining of life that bridges science, philosophy, cybernetics, and the complexities of biological existence The Organism Is a Theory: Giuseppe Longo on Biology, Mathematics, and AI (Giuseppe Longo and Adam Nocek, 2026) is an intriguing synthesis of decades of interdisciplinary research by eminent mathematician and biological scientist Giuseppe Longo. A unique collaboration between Longo and philosopher of technology Adam Nocek, the volume confronts foundational issues in the history of mathematics, computer science, physics, and theoretical biology. Challenging conventional approaches that apply computational and formalist models to the biological world, Longo reveals how the limitations of these models hinder the understanding of organismic complexity, development, and evolution. Through a critique of dominant scientific paradigms, he emphasizes the need for a new biological theory that accounts for the temporal and spatial intricacies of life. Enhanced by Nocek's comprehensive introduction and a fascinating three-part interview with Longo, The Organism Is a Theory offers a bold rethinking of the biosciences, integrating the work of Alan Turing, Bernhard Riemann, Henri Poincaré, Kurt Gödel, and others into Longo's vision of critical biology. Bridging scientific and philosophical discourses, this book creatively applies insights from mathematics, physics, and computing into the study of the organism to present a new theoretical approach to understanding biological complexity that resists reductive mechanistic and informatic explanations. Retail e-book files for this title are screen-reader friendly with image accompanied by short alt text and/or extended description. Learn more about your ad choices. Visit megaphone.fm/adchoices Support our show by becoming a premium member! https://newbooksnetwork.supportingcast.fm/technology

A bold reimagining of life that bridges science, philosophy, cybernetics, and the complexities of biological existence The Organism Is a Theory: Giuseppe Longo on Biology, Mathematics, and AI (Giuseppe Longo and Adam Nocek, 2026) is an intriguing synthesis of decades of interdisciplinary research by eminent mathematician and biological scientist Giuseppe Longo. A unique collaboration between Longo and philosopher of technology Adam Nocek, the volume confronts foundational issues in the history of mathematics, computer science, physics, and theoretical biology. Challenging conventional approaches that apply computational and formalist models to the biological world, Longo reveals how the limitations of these models hinder the understanding of organismic complexity, development, and evolution. Through a critique of dominant scientific paradigms, he emphasizes the need for a new biological theory that accounts for the temporal and spatial intricacies of life. Enhanced by Nocek's comprehensive introduction and a fascinating three-part interview with Longo, The Organism Is a Theory offers a bold rethinking of the biosciences, integrating the work of Alan Turing, Bernhard Riemann, Henri Poincaré, Kurt Gödel, and others into Longo's vision of critical biology. Bridging scientific and philosophical discourses, this book creatively applies insights from mathematics, physics, and computing into the study of the organism to present a new theoretical approach to understanding biological complexity that resists reductive mechanistic and informatic explanations. Retail e-book files for this title are screen-reader friendly with image accompanied by short alt text and/or extended description. Learn more about your ad choices. Visit megaphone.fm/adchoices Support our show by becoming a premium member! https://newbooksnetwork.supportingcast.fm/new-books-network

A bold reimagining of life that bridges science, philosophy, cybernetics, and the complexities of biological existence The Organism Is a Theory: Giuseppe Longo on Biology, Mathematics, and AI (Giuseppe Longo and Adam Nocek, 2026) is an intriguing synthesis of decades of interdisciplinary research by eminent mathematician and biological scientist Giuseppe Longo. A unique collaboration between Longo and philosopher of technology Adam Nocek, the volume confronts foundational issues in the history of mathematics, computer science, physics, and theoretical biology. Challenging conventional approaches that apply computational and formalist models to the biological world, Longo reveals how the limitations of these models hinder the understanding of organismic complexity, development, and evolution. Through a critique of dominant scientific paradigms, he emphasizes the need for a new biological theory that accounts for the temporal and spatial intricacies of life. Enhanced by Nocek's comprehensive introduction and a fascinating three-part interview with Longo, The Organism Is a Theory offers a bold rethinking of the biosciences, integrating the work of Alan Turing, Bernhard Riemann, Henri Poincaré, Kurt Gödel, and others into Longo's vision of critical biology. Bridging scientific and philosophical discourses, this book creatively applies insights from mathematics, physics, and computing into the study of the organism to present a new theoretical approach to understanding biological complexity that resists reductive mechanistic and informatic explanations. Retail e-book files for this title are screen-reader friendly with image accompanied by short alt text and/or extended description. Learn more about your ad choices. Visit megaphone.fm/adchoices Support our show by becoming a premium member! https://newbooksnetwork.supportingcast.fm/science

A bold reimagining of life that bridges science, philosophy, cybernetics, and the complexities of biological existence The Organism Is a Theory: Giuseppe Longo on Biology, Mathematics, and AI (Giuseppe Longo and Adam Nocek, 2026) is an intriguing synthesis of decades of interdisciplinary research by eminent mathematician and biological scientist Giuseppe Longo. A unique collaboration between Longo and philosopher of technology Adam Nocek, the volume confronts foundational issues in the history of mathematics, computer science, physics, and theoretical biology. Challenging conventional approaches that apply computational and formalist models to the biological world, Longo reveals how the limitations of these models hinder the understanding of organismic complexity, development, and evolution. Through a critique of dominant scientific paradigms, he emphasizes the need for a new biological theory that accounts for the temporal and spatial intricacies of life. Enhanced by Nocek's comprehensive introduction and a fascinating three-part interview with Longo, The Organism Is a Theory offers a bold rethinking of the biosciences, integrating the work of Alan Turing, Bernhard Riemann, Henri Poincaré, Kurt Gödel, and others into Longo's vision of critical biology. Bridging scientific and philosophical discourses, this book creatively applies insights from mathematics, physics, and computing into the study of the organism to present a new theoretical approach to understanding biological complexity that resists reductive mechanistic and informatic explanations. Retail e-book files for this title are screen-reader friendly with image accompanied by short alt text and/or extended description. Learn more about your ad choices. Visit megaphone.fm/adchoices

This episode of Vermont Viewpoint was published 01/19/2026.

Most stress is not caused by the moment. It is caused by the inner patterns we keep repeating. In Healthy Mind, Healthy Life, host Sayan sits down with Debbie Longo to unpack how these hidden patterns shape stress, emotions, and daily choices. This episode is for anyone stuck in anxiety loops, people-pleasing, overthinking, or burnout, even when life looks “fine.” You will learn how to spot the real driver behind the behavior, pause before spiraling, and use simple tools like breathwork, meditation, and support to feel calmer and more grounded. About the Guest: Debbie Longo is a coach who shares insights from her lived experience and 25 years working with clients. She focuses on identifying the roots behind everyday stress patterns and helping people shift them through practical, simple changes. Key Takeaways: Notice the repeated stress trigger, not just the stressful event Learned behaviors often start in childhood, but they can also come from adult loss or trauma Treat the root cause (like ego or fear), not only the visible symptom When you feel “off,” stop, find quiet, and name what you are choosing instead Use daily breathing or a simple meditation practice to regulate your nervous system If you feel stuck, get support from a coach or professional you trust How to Connect With the Guest: Website: https://lifeinbloomny.net/  LinkedIn: Debbie Longo Podcast: Behavioral Profit Upcoming: Life Coach for Anybody Want to be a guest on Healthy Mind, Healthy Life? DM on PM - Send me a message on PodMatch DM Me Here: https://www.podmatch.com/hostdetailpreview/avik Disclaimer: This video is for educational and informational purposes only. The views expressed are the personal opinions of the guest and do not reflect the views of the host or Healthy Mind By Avik™️. We do not intend to harm, defame, or discredit any person, organization, brand, product, country, or profession mentioned. All third-party media used remain the property of their respective owners and are used under fair use for informational purposes. By watching, you acknowledge and accept this disclaimer. Healthy Mind By Avik™️ is a global platform redefining mental health as a necessity, not a luxury. Born during the pandemic, it's become a sanctuary for healing, growth, and mindful living. Hosted by Avik Chakraborty, storyteller, survivor, and wellness advocate. With over 6000+ episodes and 200K+ global listeners, we unite voices, break stigma, and build a world where every story matters.

Welcome to "Random Fit" and the latest episode, “Part I: The Goldilocks Principle of Fitness – Finding Your ‘Just Right' for Change.” If you've ever wondered why some fitness routines work wonders for some and knock others out—or why making smart choices with food, exercise, and recovery matters more than ever—this is the episode you can't afford to miss. Join award-winning hosts and industry pros Wendy Batts, and Ken Miller, as they launch their five-part “Fitness Fairy Tales” series by digging into the famous Goldilocks Principle. Discover how fairy tale wisdom helps you cut through overwhelming health advice and zero in on the optimal “just right” zone to spark real, lasting body transformation. Curious about high-intensity interval training (HIIT), intermittent fasting, cold showers, sauna sessions, and weightlifting? Wendy and Ken break down the science behind hormesis—how the right dose of challenge can make you stronger, fitter, and healthier, while too much or too little can leave you stuck or even injured. You'll get actionable insights on maximizing your health span—not just lifespan—so you're thriving, not just surviving. Get the inside scoop on cellular adaptation, muscle growth, recovery secrets, and holistic well-being so you feel and perform better, longer. Perfect for fitness enthusiasts, trainers, and anyone seeking practical health tips grounded in real science and informed coaching.Get ready to transform the way you think about fitness, forever! Episode References: Godfrey, R. J., et al. (2008). The exercise-induced growth hormone response in athletes. Sports Medicine, 38(2), 167–193.Longo, V. D., & Mattson, M. P. (2014). Fasting: molecular mechanisms and clinical applications. Cell Metabolism, 19(2), 181–192.  If you like what you just consumed, leave us a 5-star review, and share this episode with a friend to help grow our NASM health and wellness community! The content shared in this podcast is solely for educational and entertainment purposes. It is not intended to be a substitute for professional advice, diagnosis, or treatment. Always seek out the guidance of your healthcare provider or other qualified professional. Any opinions expressed by guests and hosts are their own and do not necessarily reflect the views of NASM. Introducing NASM One, the membership for trainers and coaches. For just $35/mo., get unlimited access to over 300 continuing education courses, 50% off additional certifications and specializations, EDGE Trainer Pro all-in-one coaching app to grow your business, unlimited exam attempts and select waived fees. Stay on top of your game and ahead of the curve as a fitness professional with NASM One. Click here to learn more. https://bit.ly/4ddsgrm

On this episode of The Curious Builder Podcast, Mark Williams chats with his good friend Vincent Longo about all things building, balancing work and family, and learning from the ones that got away (including a wild story where Vince literally got knocked to the ground by fate!). They swap stories about growing their businesses, keeping family first, and even throw in some fun ideas like gap years and house signing parties. To top it off, Vince gives us some live play-by-play while he bids—and hilariously loses—on a house during the podcast. Support the show - https://www.curiousbuilderpodcast.com/shop See our upcoming live events - https://www.curiousbuilderpodcast.com/events The host of the Curious Builder Podcast is Mark D. Williams, the founder of Mark D. Williams Custom Homes Inc. They are an award-winning Twin Cities-based home builder, creating quality custom homes and remodels — one-of-a-kind dream homes of all styles and scopes. Whether you're looking to reimagine your current space or start fresh with a new construction, we build homes that reflect how you live your everyday life. Sponsors for the Episode:  Pella Website: https://www.pella.com/ppc/professionals/why-wood/  Sauna Camp Website: https://www.saunacamps.com/ Where to find the Guest:  Website: https://longocustombuilders.com Instagram: https://www.instagram.com/longocustombuilders/ YouTube: https://www.youtube.com/@buildingbrewsandbbq  Where to find the Host:  Website - https://www.mdwilliamshomes.com/  Podcast Website - https://www.curiousbuilderpodcast.com Instagram - https://www.instagram.com/markdwilliams_customhomes/  Facebook - https://www.facebook.com/MarkDWilliamsCustomHomesInc/  LinkedIn - https://www.linkedin.com/in/mark-williams-968a3420/  Houzz - https://www.houzz.com/pro/markdwilliamscustomhomes/mark-d-williams-custom-homes-inc

What if life isn't hard — but the way we perceive it makes it feel that way?

PAULO REZZUTTI e JOÃO PEDRO RANGEL são historiadores. Eles vão bater um papo sobre fake news mais famosas da história mundial. O Vilela pode dizer se foram fake news ou não, já que esteve presente na maioria delas.

NESTA EDIÇÃO. Restauração prometida por Trump na Venezuela indica que intervenção deve ser longa. China pode ficar mais reticente em fazer negócios na América Latina, indicam especialistas. Produção brasileira de petróleo chega a 4,9 milhões de boe/dia em novembro. ***Locução gerada por IA

Professor Matthew Longo. Longo details the geopolitical backdrop of 1989, focusing on Hungarian Prime Minister Miklós Németh. He explains Németh's clash with Romania's Ceaușescu and a pivotal, secret meeting with Gorbachev, where Németh received tacit approval to dismantle the Iron Curtain's physical border defenses. 1960S

Professor Matthew Longo. Longo shifts focus to "radical nobodies," specifically activists Ferenc and Maria, who conceived the Pan-European Picnic. He describes their audacious, naive plan to host a party at the lethal Iron Curtainborder near Sopron, intending to celebrate European togetherness and unwittingly sparking a major historical event. NOVEMBER 1961 BERLIN

Professor Matthew Longo. Longo describes the tension at the campsite where East German refugees, monitored by Stasi agents, gathered. He recounts the chaotic border breakthrough, highlighting the moral choice of Hungarian guards who allowed refugees to cross into Austria rather than shooting, marking a bloodless victory for freedom. 2016 GERMANY

Professor Matthew Longo. Reflecting on the site thirty years later, Longo discusses the philosophical implications of freedom using Isaiah Berlin and Hannah Arendt. He contrasts Western "negative liberty" with the solidarity desired by East Germans, noting how the former borderland has transformed into an unremarkable green belt. 1985 CZECH FRONTIER

Show notes: (0:00) Intro (0:56) Dr. Longo's surprising path from music student to aging expert (2:00) Early yeast studies and the 10x lifespan breakthrough (3:56) Launching the Fasting Mimicking Diet and supporting clinical trials (6:15) The dangers of long-term calorie restriction and yo-yo dieting (12:18) Why 12-hour fasting is safer than 16+ hours (18:22) Key differences in fasting for women (20:52) What's actually in the Fasting Mimicking Diet (23:41) How often to do it and who benefits most (28:47) Regenerating organs with stem cells and fasting (34:55) The Longevity Diet (38:11) Legumes, protein levels, and real-world advice (45:08) Fasting and cancer: what early research shows (48:15) Where to learn more from Dr. Longo (49:00) Outro   Who is Dr. Valter Longo?   Dr. Valter Longo is the Edna M. Jones Professor of Gerontology and Biological Sciences and Director of the Longevity Institute at the USC Leonard Davis School of Gerontology, a leading center for aging and disease research. Trained in biochemistry at the University of North Texas and UCLA, with postdoctoral work under longevity pioneers Roy Walford and Caleb Finch, Dr. Longo has built a multidisciplinary research career spanning genetics, immunology, endocrinology, and molecular biology. His laboratory has identified key genetic pathways that regulate aging and demonstrated how targeting these pathways can reduce disease risk and progression in both animal models and humans, including novel dietary and genetic strategies that protect healthy cells while making cancer cells more vulnerable to treatment.   Dr. Longo is widely known for developing the fasting mimicking diet, a five-day periodic dietary intervention shown in randomized clinical trials to reduce markers associated with aging and chronic disease, while promoting stem cell–based regeneration and longevity. His work has earned numerous prestigious awards, including the Glenn Award for Aging Research, and in 2018 he was named one of Time Magazine's 50 most influential people in health care. Deeply committed to public health and accessibility, Dr. Longo donates all proceeds from his bestselling books, including The Longevity Diet and Fasting Cancer, to research and education through his foundations in Milan and Los Angeles, advancing affordable strategies to prevent disease and extend healthy lifespan. Connect with Dr. Longo: Website: https://valterlongo.com/                 https://l-nutra.com/ Facebook: https://www.facebook.com/profvalterlongo/ IG: https://www.instagram.com/prof_valterlongo/   Grab a copy: https://tinyurl.com/4h4mspmt                        https://tinyurl.com/j23u989b Links and Resources: Peak Performance Life Peak Performance on Facebook Peak Performance on Instagram

Mike sits down with Lawrence Longo, a serial food and hospitality entrepreneur whose journey from hidden menu curator to restaurant empire builder has reshaped how people connect through food. Lawrence shares how his early obsession with experience over ego led him from launching Off the Menu — a community built around secret dishes and insider dining — to reviving Irv's Burgers, expanding Prince St. Pizza nationwide, and building a hospitality group that's redefining what "premium fast food" really means. They dive into the lessons learned from scaling beloved brands without losing their soul, the role of storytelling and community in hospitality, and what travel and culture have taught Lawrence about simplicity, obsession, and belonging. This episode isn't just about food — it's about the universal language of connection, the places that shape us, and the people who keep showing up for what feels real. Chapters: 00:00 – From hidden menus to hospitality visionary 05:00 – The story behind Off the Menu and food as connection 10:00 – Reviving Irv's Burgers and honoring old-school soul 15:00 – Expanding Prince St. Pizza without losing authenticity 20:00 – Scaling restaurants while keeping local roots 25:00 – Simplicity, obsession, and the power of hospitality 30:00 – Partner alignment and trusting local voices 35:00 – The community mindset behind every concept 40:00 – The travel that shaped a hospitality entrepreneur 45:00 – What it really means to build brands people love

Nicola Longo MD, PhD, and Mark Roberts, MD Nicola Longo MD, PhDProfessor and Vice Chair of Human Genetics,Allen and Charlotte Ginsburg Chair in Precision Genomic Medicine,Division of Clinical Genetics, Department of Human Genetics,University of California at Los Angeles (UCLA), Los Angeles, CA, USAMark Roberts, MDProfesor and Consultant Neurologist,University of Manchester, Manchester, UKResearch Lead for Adult Metabolic Medicine at Salford Care Organisation, Manchester, UKDrs. Longo and Roberts discuss the current status of gene therapies in rare neuromuscular disorders in this eight-part podcast series. This is derived from the symposium that was presented at World Symposium 2025 in San Diego, California on February 4th through 7th, 2025 and is intended for healthcare professionals only. This podcast includes information about investigational compounds that do not yet have a regulatory approval or authorization for a specific indication. The safety and efficacy of the agents under investigation have not been established and contents of this podcast shall not be used in any manner to directly or indirectly promote or sell the product for unapproved uses. The views, thoughts, and opinions expressed in this presentation belong solely to the author and are subject to change without notice.The contents of this presentation do not constitute an endorsement of any product or indication by Astellas. In this part, Dr. Roberts will discuss vectors, different strategies, modes of administration and targets in gene replacement therapies.Mark Roberts, MDNow in the broader sense, gene replacement therapy seeks to actually deliver genetic material directly into the host cell to influence gene expression. In the most simple idea, one of course has a vector, this is most commonly but not exclusively a virus, which can then be given intravenously for example, and can hope to potentially correct the condition within the individual cells using novel transgenes. Suitable candidate conditions for this as examples of genetic conditions are now well understood. And crucially, this applies not only towards some more recessive, but dominant and even accident conditions.Across the piece, one can see for example, mitochondrial problems, spinal muscular atrophy as is well known, X-linked myotubular myopathy, Duchenne muscular dystrophy, a very common condition affecting one in 3000 male individuals, Pompe disease of course, an important focus of the meeting here, but other very common conditions, for example, cystic fibrosis, immunological conditions and perhaps obviously very crucial in early work on gene therapy, hemophilia.Let's now think about the approaches to gene therapy. One can seek to work at the DNA level and gene replacement. In essence, one is trying to put a new transgene through into the nucleus that will ultimately be transcribed and translated and produce the important functional protein that is lost. Gene editing which is a very exciting new technology or CRISPR technology actually seeks to actually modify in vivo the actual mutations that are responsible for the pathogenic production of abnormal proteins and correcting these and actually producing a more normalized protein.But of course there are also RNA approaches where one seeks to actually repair the mRNA transcripts copied from the mutated gene. For example, this may be a novel approach that could be extremely useful in myotonic dystrophy, a multisystem condition. When we talk about the viral vectors, predominantly we're talking about viruses. Those such as adenoviruses and AAV viruses which have the virtue of not integrating into the host genome or at least not in a large amount, and those which deliberately seek to integrate into host genome such as retroviral or lentiviral systems that may be particularly useful for ex vivo systems.There are of course other ways to get genetic payloads into the nucleus, various polymers, nanoparticles and even cell penetrating peptides. Nanoparticles in particular is certainly on the ascendant. That being said, in a recent review of the clinical trials in gene therapy, it was certainly the viral vectors that stood out both in direct gene replacement with lentivirus and AAV, but also actually as delivery systems, for example, for gene editing. An example of what one is seeking to do with AAV, so of course one seeking to remove the native DNA, insert the new transgene directly into the vector and of course keen to make sure that there's a high transmission into the capsid producing a recombinant AAV, which then can be given as a treatment and hopefully produce a therapeutic increase in the functional protein that is deficit in the disorder.In the next part, Dr. Roberts will discuss immune responses and other safety concerns related to gene therapies.

Nicola Longo MD, PhD, and Mark Roberts, MDNicola Longo MD, PhDProfessor and Vice Chair of Human Genetics,Allen and Charlotte Ginsburg Chair in Precision Genomic Medicine,Division of Clinical Genetics, Department of Human Genetics,University of California at Los Angeles (UCLA), Los Angeles, CA, USAMark Roberts, MDProfesor and Consultant Neurologist,University of Manchester, Manchester, UKResearch Lead for Adult Metabolic Medicine at Salford Care Organisation, Manchester, UKDrs. Longo and Roberts discuss the current status of gene therapies in rare neuromuscular disorders in this 8-part podcast series. This is derived from the symposium that was presented at World Symposium 2025 in San Diego, California on February 4th-7th 2025 and is intended for healthcare professionals only.This podcast includes information about investigational compounds that do not yet have a regulatory approval or authorization for a specific indication. The safety and efficacy of the agents under investigation have not been established and contents of this podcast shall not be used in any manner to directly or indirectly promote or sell the product for unapproved uses.The views, thoughts, and opinions expressed in this presentation belong solely to the author and are subject to change without notice. The contents of this presentation do not constitute an endorsement of any product or indication by Astellas. In this part, Dr. Roberts will discuss immune responses and other safety concerns related to gene therapies.Mark Roberts, MDUndoubtedly, the immune system is a major issue in these patients. It would be fantastic if we could immunotolerize our patients and indeed prevent the rejection of the therapy. We've talked about the fact that these are viral vectors and of course there may be high seroprevalence of antibodies to these viral vectors, and it's very important in the pre-screening of patients who might be eligible to understand that at the beginning. These of course can have developed over the years and of course can be part of immunological memory and therefore extremely difficult and probably impractical to actually shift.On giving the treatment though as I think we're all aware there is this problem of the innate immunity and potential therefore for acute toxicities and then a learned or adaptive response with cytotoxic T cells and antibodies which may of course become high tighter neutralizing antibodies and potentially antibodies not only against the viral vector, even the functional protein, even the transgene are all theoretical possibilities with time. The capsid, the transgene, and even the protein product can all potentially induce an immunological event. Of course, all of these would lead to both potential patient changes and then a lack of efficacy of the treatment.Indeed, there have been some serious and indeed fatal problems in the gene therapy development program as I think we're all aware. Though many of these are thankfully been overcome. Spinal muscular atrophy has a gene therapy which is licensed, but there were early patients who actually had significant problems. A patient of just 6 months of age who developed kidney failure, two other patients who actually developed liver failure.In Duchenne muscular dystrophy, a very common condition, again there were significant issues and crucially in these patients who all have cardiomyopathy, it was heart failure and cardiac arrest that were big concerns and pulmonary edema and this was seen even with a CRISPR-based technology and is perhaps is best known but has been addressed the excellent myotubular myopathy patients, four patients died and crucially quite a long time after the gene therapy emphasizing the need to monitor these patients extremely carefully and these patients died of cholestatic liver failure albeit that they had a degree of liver dysfunction.That's changed our screening of course of patients, we're now all looking in myotubular patients for liver involvement and Rett syndrome as well. Now these immunoprophylaxis treatment regimes to hopefully try and reduce the immunological reaction against the gene are certainly evolving.This is just a summary of some of the other immunosuppressive regimes used in other disorders, for example, spinal muscular atrophy, but Pompe and MPS as examples of LSDs. Certainly these regimes will continue to evolve and are going to be very important in seeking to make sure that these treatments are effective. It reminds me somewhat of what's happened with enzyme replacement therapy that the use of these immunological strategies in infants has revolutionized the utility of those treatments in early patients.In the next part, Dr. Roberts will discuss lessons learned from gene therapy trials.

Nicola Longo MD, PhD, and Mark Roberts, MDNicola Longo MD, PhDProfessor and Vice Chair of Human Genetics,Allen and Charlotte Ginsburg Chair in Precision Genomic Medicine,Division of Clinical Genetics, Department of Human Genetics,University of California at Los Angeles (UCLA), Los Angeles, CA, USAMark Roberts, MDProfessor and Consultant Neurologist,University of Manchester, Manchester, UKResearch Lead for Adult Metabolic Medicine at Salford Care Organisation, Manchester, UKDrs.Longo and Roberts discussed the current status of gene therapies in rare neuromuscular disorders in this eight-part podcast series. This is derived from the symposium that was presented at World Symposium 2025 in San Diego, California on February 4th through 7th, 2025 and is intended for healthcare professionals only.This podcast includes information about investigational compounds that do not yet have a regulatory approval or authorization for a specific indication. The safety and efficacy of the agents under investigation have not been established and contents of this podcast shall not be used in any manner to directly or indirectly promote or sell the product for unapproved uses. The views, thoughts, and opinions expressed in this presentation belong solely to the author and are subject to change without notice. The contents of this presentation do not constitute an endorsement of any product or indication by Astellas.In this part, Dr. Roberts will discuss lessons learned from gene therapy trials.Mark Roberts, MDWhen we think about the challenges of actually doing clinical trials with these gene therapies, there's a huge development stage in terms of picking the right viral vector with the right surface receptor. That's a major piece of work. That can often take years. The preclinical work is obviously very important as indeed is understanding the natural history because it's really not practical to do placebo-controlled trials of gene therapies.In contrast to other studies, when we turn to phase 1 and phase 2, you'll notice that the patient numbers are often quite small. One is having to think carefully about surrogate measurements of response. Especially when in phase 3 studies, we may be thinking about withdrawing the existing, for example, enzyme replacement therapy because we believe the gene therapy will then be effective.That's just a few snapshots of where we've come and there's a lot more work to be done.In the next part, Dr. Longo will discuss the current treatment landscape and limitations in lysosomal disorders.

Nicola Longo MD, PhD, and Mark Roberts, MDDrs. Longo and Roberts discuss the current status of gene therapies in rare neuromuscular disorders in this eight-part podcast series. This is derived from the symposium that was presented at WORLDSymposium 2025 in San Diego, California on February 4th-7th 2025 and is intended for healthcare professionals only.This podcast includes information about investigational compounds that do not yet have a regulatory approval or authorization for a specific indication. The safety and efficacy of the agents under investigation have not been established and contents of this podcast shall not be used in any manner to directly or indirectly promote or sell the product for unapproved uses.The views, thoughts, and opinions expressed in this presentation belong solely to the author and are subject to change without notice. The contents of this presentation do not constitute an endorsement of any product or indication by Astellas. In this part, Dr. Longo will discuss the current treatment landscape and limitations in lysosomal disorders.Nicola Longo MD, PhDWhat I want to do today, is just place gene replacement therapy within the current landscape of lysosomal storage disorder treatment therapy. Gene therapy obviously has the potential of treating lysosomal disorder to correct the root cause of lysosomal storage disorder. The gene is defective, and what happen is that you can potentially either fix the gene or bypass the lack of the genetic product. But there are already therapies that are existing and are functioning. Obviously, in many cases, the lysosomal disorder is caused by defective production of an enzyme, which is defective.We can either replace the enzyme with enzyme replacement therapy, or provide chaperone for specific mutations that retain the synthesis of the enzyme, that however is not very functional. Another avenue that it is being reported is the utilization of substrate reduction therapy. A substrate accumulates, you prevent the synthesis of the substrate to reduce the accumulation of toxic material. What we know now is that this is not enough to produce many lysosomal disorders. In many cases, the lysosomal disorder result sometime in impairment of intracellular trafficking, and sometime in the function of other organelles.At the end, it results in the activation of the macrophagic system and inflammation. Already we have some therapy acting at this level. The end result of lysosomal storage disorder, there will be cell suffering and cell death, leading to a progression of the disease, and morbidity and mortality. Now, what therapy do we have available already? Obviously, hematopoietic stem cell transplantation has been around for quite some time.It has been the same thing that we do with gene therapy, except that instead of reintroducing the gene of the subject, we place gene of a subject who is not affected of the disease. This therapy has been proven effective in cases of MPS-1 and alpha-mannosidosis. But in many cases this has to be given way before symptoms start to be affected.Enzyme replacement therapy has been around for quite some time, starting with Gaucher disease, and now that it is available for a list of diseases that are there, so it's like Fabry, Gaucher, Pompe, different types of mucopolysaccharidosis, alpha-mannosidosis, acid lipase deficiency, 1 neuronal ceroid lipofuscinosis, and Niemann-Pick type A and B.Obviously the advantage of this therapy, they give back the enzyme that it is defective. But the disadvantage that many time they cannot enter specialized areas such as the brain. There is already the second generation of enzyme replacement therapy that it is available. With this second generation, some of the newer drugs are more effective in terms of cellular uptake, or in terms of having a prolonged half-life and prolonged activity.Then there are pharmacological chaperone therapy, and the one which is FDA approved is migalastat for Fabry disease, under study is ambroxol for Gaucher disease. The disadvantage of this therapy that only a selected number of mutations respond to this therapy.Substrate reduction therapy has been introduced for Gaucher disease many years ago with miglustat, and it was followed by eliglustat. Both of them are effective, and some of them more effective than other, simply because of the fewer side effects of eliglustat as compared to miglustat. But at the same time, eliglustat does not pass the blood brain barrier.Finally, the newer agents that are already administered, N-acetyl-L-leucine and arimoclomol, both approved for Niemann-Pick type C, they act more on the downstream effect of the lysosomal storage disorder, either by stabilizing neuronal cell activity or by reducing the inflammation that is present in the brain.In the next part, Dr. Longo will discuss gene replacement therapy in lysosomal disorders.

Nicola Longo MD, PhDProfessor and Vice Chair of Human Genetics,Allen and Charlotte Ginsburg Chair in Precision Genomic Medicine,Division of Clinical Genetics, Department of Human Genetics,University of California at Los Angeles (UCLA), Los Angeles, CA, USAMark Roberts, MDProfessor and Consultant Neurologist,University of Manchester, Manchester, UKResearch Lead for Adult Metabolic Medicine at Salford Care Organisation, Manchester, UKDrs. Longo and Roberts discussed the current status of gene therapies in rare neuromuscular disorders in this eight part podcast series. This is derived from the symposium that was presented at World Symposium 2025, in San Diego, California, on February 4th through 7th, 2025, and is intended for healthcare professionals only. This podcast includes information about investigational compounds that do not yet have a regulatory approval or authorization for a specific indication. The safety and efficacy of the agents under investigation have not been established, and contents of this podcast shall not be used in any manner to directly or indirectly promote or sell the product for unapproved uses. The views, thoughts and opinions expressed in this presentation belong solely to the author and are subject to change without notice. The contents of this presentation do not constitute an endorsement of any product or indication by Astellas. In this part, Dr. Longo will discuss gene replacement therapy in lysosomal disorders.Nicola Longo MD, PhDLet's go back a second to gene therapy. Gene therapy obviously has the potential of answering many of the questions that we still have open in lysosomal disorder because they could restore the activity of the lysosome pretty much in the whole body, or at least in multiple tissues. As you have seen, gene therapy can be done ex vivo where we take cells from the affected patient, we correct the gene, or we put an extra gene that it is functional. Then we put them back by doing a bone marrow transplant, basically creating space for the cells that have been genetically modified to correct the lysosomal defect. The biggest approach this is done usually by lentiviruses that they integrate inside the genome.

Nicola Longo MD, PhDProfessor and Vice Chair of Human Genetics,Allen and Charlotte Ginsburg Chair in Precision Genomic Medicine,Division of Clinical Genetics, Department of Human Genetics,University of California at Los Angeles (UCLA), Los Angeles, CA, USAMark Roberts, MDProfessor and Consultant Neurologist,University of Manchester, Manchester, UKResearch Lead for Adult Metabolic Medicine at Salford Care Organisation, Manchester, UKDrs. Longo and Roberts discussed the current status of gene therapies in rare neuromuscular disorders in this eight-part podcast series. This is derived from the symposium that was presented at World Symposium 2025 in San Diego, California on February 4th through 7th, 2025, and is intended for healthcare professionals only. This podcast includes information about investigational compounds that do not yet have a regulatory approval or authorization for a specific indication. The safety and efficacy of the agents under investigation have not been established and contents of this podcast shall not be used in any manner to directly or indirectly promote or sell the product for unapproved uses. The views, thoughts, and opinions expressed in this presentation belong solely to the author and are subject to change without notice. The contents of this presentation do not constitute an endorsement of any product or indication by Astellas. In this part, Dr. Longo will discuss ongoing gene therapies in lysosomal disorders.Nicola Longo MD, PhDI'm going to present to discuss some example of ongoing gene therapy for lysosomal disorder. There are gene therapy in development for both Fabry disease and some of this involve ex vivo gene therapy, many others involve systemic administration with an AAV, Gaucher disease type 1 that affect the periphery, and Gaucher disease type 2, where the replacement should occur within the central nervous system because this condition affects the brain. There is already one approved gene therapy for lysosomal disorder, which is for the early onset metachromatic leukodystrophy. This has been approved both in Europe and now even in the United States, which consists of ex vivo gene therapy with the administration of an extra gene that restore the function of the defective enzyme. Now there are many others that are ongoing for the same indication. There are gene therapy programs for GM1 and GM2 gangliosidosis, and at least one for Krabbe disease. It is important to know that some of these condition are actually included in the recommended uniform screening panel. Basically, we would have access to patients in a timely manner for some of these conditions. Then there are several gene therapy under development for the mucopolysaccharidoses, including MPS-IH, MPS-II, MPS-IIIA and MPS-IV.There are different type of lysosomal disorders, the one caused by mutation, integral membrane protein, not enzyme within the lysosome, but protein that are present on the membrane of the lysosome. This gene therapy that have been tested, it is for cystinosis, that it is caused by a defective lysosomal and for Danon disease, which is caused by a deficiency of an integral membrane part. Finally, one lysosomal disorder, which obviously seems a metabolic condition, but it is really not, is glycogen storage disease type 2 or Pompe disease, in which there is the intralysosomal accumulation of glycogen. There are several ongoing clinical trials to try to correct the problem in this condition.Now, I'm going to discuss some of the most advanced program in the lysosomal storage disorder. This include one for Fabry, which is on an accelerated approval pathway with phase 1 and 2 data, one for Gaucher disease type 1. Obviously, I'm going to discuss the one that has been already approved for metachromatic leukodystrophy. There is one for Hunter syndrome, and the difference of the one for Hunter syndrome, it is an example of the direct administration of gene therapy within the central nervous system.Finally, there is one ongoing for glycogen storage disease type 2 or Pompe disease in adult patients. In gene therapy for metachromatic leukodystrophy, it was the first gene therapy approved for lysosomal disorder in human, and this requires harvesting the CD34 cell from affected patient and then introducing the [inaudible 00:04:32] gene back in this cell, and then placing them back inside the patient again. This has been very effective in patients who were treated early, and obviously, the treatment needs to occur before there is irreversible brain damage in this patient.In the next part, Dr. Roberts and Longo will discuss treatment with gene therapies.

When Lawrence Longo launched the Off the Menu app, he was not envisioning becoming one of the most prolific restaurateurs in Los Angeles. Yet a decade later, that's exactly where we are. Lawrence is responsible for the birth of Prince St. Pizza in Los Angeles, rescuing beloved stalwart Irv's Burgers, launching Tacos 1986 & even pioneering the smashburger craze with Burgers Never Say Die. Truly a fascinating character with a unique & fun origin story.

Renee Fitton is a registered dietitian, entrepreneur, and expert in nutrition, longevity, and healthcare innovation. She specializes in fasting-mimicking diets, cellular renewal, and bridging scientific research with practical health applications.  She is the Director of Education & Healthcare Sales at ProLon, where she develops sales strategies, educates healthcare practitioners on nutrition and longevity science, and promotes fasting-mimicking diets. She also serves as a Medical Science Liaison (since April 2023). 0.00:    Renee's background as a longevity dietician 8.00:    The power of diet 10.00:  The power of Fasting 14.00:  Why Fasting Mimicking diets are so powerful (Dr. Longo) 21.00: How Fasting Mimicking has insignificant muscle loss 26.00:  How to eat healthy 31.00:  Intermittent fasting (AM versus PM) 41.00: Ideal Evening Meal before athletic events 45.00:  Supporting autophagy and cellular cleanup only in longer fasts 50.00:  Coming off a longer fast/ fasting mimicking diet 56.00:  Meat for athletic performance vs longevity 1.01.00: Different protein powder sources (and L-Protein) Renee on IG: @fitonnutrition Prolon website: https://prolonlife.com/ Until next time, love and good vibes.  Podcast Website: https://enterthelionheart.com/ Check out the latest episode here: Apple Podcast: https://podcasts.apple.com/us/podcast/enter-the-lionheart/id1554904704 Spotify: https://open.spotify.com/show/4tD7VvMUvnOgChoNYShbcI