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In this “Ask Me Anything” (AMA) episode, Peter dives back into the increasingly popular topic of GLP-1 agonists, such as Ozempic and Mounjaro, which have garnered widespread attention for their ability to promote weight loss. Peter covers the latest findings in this rapidly evolving landscape, including new insights into their long-term efficacy, side effects, and what happens when the drug is discontinued. Peter also explores their impact on body composition and how resistance training interacts with these treatments. Additionally, he compares different GLP-1 receptor agonists and discusses promising new drugs in the pipeline. Finally, Peter addresses questions about the role of compounding pharmacies in the GLP-1 agonist market, compares oral vs. injectable options, and provides key considerations for anyone deciding whether to use a GLP-1 agonist for weight loss.

If you’re not a subscriber and are listening on a podcast player, you’ll only be able to hear a preview of the AMA. If you’re a subscriber, you can now listen to this full episode on your private RSS feed or our website at the AMA #64 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.

We discuss:

• The rapidly evolving landscape of GLP-1 agonists [2:15];
• The mechanism of GLP-1 agonists, their origin as diabetes treatments, and how they evolved into weight-loss drugs [6:45];
• Overview of new data and open questions related to the benefits and risks of GLP-1 agonists [10:30];
• New insights into the long-term safety of GLP-1 agonists, side effects, and more [16:45];
• The long-term efficacy of GLP-1 agonists, financial barriers, and more [19:45];
• The mechanisms behind GLP-1 agonists' ability to promote weight loss [22:00];
• New data on body weight changes after discontinuing the drug [26:00];
• Effects of GLP-1 agonists on lean mass and body composition, and the role of protein and resistance training in preserving muscle [31:30];
• Semaglutide vs. tirzepatide: comparing benefits and side effects [36:30];
• How compounding pharmacies affect availability of GLP-1 drugs and the types of formulations that are available [39:15];
• How do oral formulations of GLP-1 drugs compare to injectable formulations? [44:15];
• How do sublingual (under tongue) formulations of GLP-1 drugs compare to injectable formulations? [46:15];
• Guidance for using compounding pharmacies to purchase GLP-1 agonists [47:15];
• Data on retatrutide—a promising new triple receptor agonist in the pipeline [50:15];
• Can GLP-1 agonists be beneficial for sleep apnea and immune function? [57:00];
• Potential neuroprotective benefits of GLP-1 agonists: impact on dementia risk [1:00:45];
• Exploring why GLP-1 agonists may reduce the risk of cancer, kidney disease, and cardiovascular disease [1:04:00];
• How GLP-1 agonists might boost fertility in women [1:10:15];
• Early indications that GLP-1 agonists may help treat substance abuse disorders [1:12:00];
• Potential health risks of GLP-1 agonists: addressing thyroid cancer concerns and the unknowns due to lack of data [1:14:00];
• Examining the potential link between GLP-1 agonists and increased depression or suicidal ideation [1:16:00];
• Major remaining questions: the effects of cyclic use, rebound appetite, impact on adolescents' development, and more [1:19:30];
• Key considerations when deciding whether to use a GLP-1 agonist for weight loss [1:23:45]; and
• More.

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In this quarterly podcast summary (QPS) episode, Peter summarizes his biggest takeaways from the last three months of guest interviews on the podcast. Peter shares key insights from each episode, covering diverse topics such as liver health with Julia Wattacheril, heart rate variability with Joel Jamieson, artificial intelligence with Zak Kohane, klotho for brain health with Dena Dubal, and lactate and lactate metabolism with George Brooks. Additionally, Peter shares any personal behavioral adjustments or modifications to his patient care practices that have arisen from these engaging discussions.

If you’re not a subscriber and are listening on a podcast player, you’ll only be able to hear a preview of the AMA. If you’re a subscriber, you can now listen to this full episode on your private RSS feed or our website at the episode #319 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.

We discuss:

• Overview of topics, and the positive feedback on the quarterly podcast summary format [2:00];
• Julia Wattacheril episode: liver health and disease [4:00];
• Noninvasive methods to diagnose liver conditions, and how to manage and improve liver health [16:00];
• Joel Jamieson episode: heart rate variability (HRV) for training and health [27:15];
• Practical tools for measuring HRV and how it informs training and recovery decisions [37:00];
• Zak Kohane episode: artificial intelligence and medicine [47:15];
• The current role of AI in medicine and how it could revolutionize medicine in the future [53:45];
• The limitations and concerns pertaining to AI [1:00:15];
• Dena Dubal episode: the potential benefits of klotho for brain health [1:05:00];
• Animal studies on klotho and brain health [1:11:00];
• Genetics-based variations in klotho levels in humans and their impact on cognition, disease risk, and longevity [1:14:15];
• Testing klotho levels, the significance of the KL-VS variant, the role of exercise in increasing klotho, and more [1:17:30];
• The potential of klotho as a treatment for cognitive decline and Alzheimer's disease [1:23:15];
• George Brooks episode: a new paradigm to think about lactate and lactate metabolism [1:27:45];
• The potential for lactate infusions to aid in brain recovery following a head injury [1:34:00];
• The relationship between lactate and cancer, and the impact of exercise on lactate levels and cancer risk [1:36:30]; and
• More.

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Tadej Pogačar is a three-time Tour de France champion and one of the most dominant cyclists of his generation. In this episode, he shares insights into his 2020 Tour de France victory, his historic 2024 season winning both the Giro d’Italia and Tour de France, and the struggles he faced in 2022 and 2023. He also dives into his training regimen, nutrition, and the key metrics he tracks, like power, VAM, and heart rate variability. Tadej offers a glimpse into his goals for the future and what it takes to stay at the top of the sport.

We discuss:

• 2020 Tour de France win [4:30];
• Learning from previous mistakes [8:45];
• Training: simulating steep climbs and other challenging race conditions [10:30];
• Tadej’s historic 2024 season and what contributed to his success [12:30];
• Nutrition for optimal performance: offseason diet and carbohydrate intake during intense training sessions [15:30];
• Training metrics: heart rate, power output, VAM, and HRV, and his approach to zone 2 training [18:15];
• Epic climbs in the Tour de France, mindset after challenging stages, and rebuilding confidence after the 2023 Tour [25:45];
• Racing dynamics, media criticism, and Tadej’s reflections on racing records [32:15];
• Training in the off-season [39:00]; and
• More.

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Marty Makary, a Johns Hopkins surgeon and New York Times bestselling author, returns to The Drive to discuss his latest book, Blind Spots: When Medicine Gets It Wrong, and What It Means for Our Health. In this episode, Marty explores how a new generation of doctors is challenging long-held medical practices by asking critical new questions. He discusses the major problems of groupthink and cognitive dissonance in the medical community and delves into several of the "blind spots" raised in the book, including treatments for appendicitis, the peanut allergy epidemic, misunderstandings about HRT and breast cancer, antibiotic use, and the evolution of childbirth. He explains the urgent need for reform in medical education and the major barriers standing in the way of innovative medical research. Throughout the conversation, Marty offers insightful reflections on where medicine has succeeded and where there’s still room to challenge historic practices and embrace new approaches.

We discuss:

• The issue of groupthink and cognitive dissonance in science and medicine [2:30];
• How a non-operative treatment for appendicitis sheds light on cognitive dissonance [7:00];
• How cognitive dissonance and effort justification shape beliefs and actions [13:15];
• How misguided peanut allergy recommendations created an epidemic [17:45];
• The enduring impact of misinformation and fear-based messaging around hormone replacement therapy allegedly causing breast cancer [25:15];
• The dangers of extreme skepticism and blind faith in science, and the importance of understanding uncertainty and probability [28:00];
• The overuse of antibiotics and the rise of antibiotic resistant infections and poor gut health [33:45];
• The potential correlations between early antibiotic use and chronic diseases [40:45];
• The historical and evolving trends in childbirth and C-section rates [50:15];
• Rethinking ovarian cancer: recent data challenging decades of medical practice and leading to new preventive measures [1:05:30];
• Navigating uncertainty as a physician [1:19:30];
• The urgent need for reform in medical education [1:21:45];
• The major barriers to innovative medical research [1:27:30];
• The dogmatic culture of academic medicine: why humility and challenging established norms are key for progress [1:38:15];
• The major successes and ongoing challenges of modern medicine [1:51:00]; and
• More.

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In this “Ask Me Anything” (AMA) episode, Peter dives deep into the topic of hair loss, exploring its relationship with aging and its impact on quality of life. The conversation focuses on androgenic alopecia, the most common form of hair loss in both men and women, and covers the differences in patterns and causes between the sexes. Peter delves into the right timing for treatment, breaking down various options such as minoxidil and finasteride, low-level laser therapy, platelet-rich plasma injections, and more. Additionally, Peter outlines the pros and cons of the two primary hair transplantation methods and concludes with practical advice on selecting the right specialist or treatment team for those facing hair loss.

If you’re not a subscriber and are listening on a podcast player, you’ll only be able to hear a preview of the AMA. If you’re a subscriber, you can now listen to this full episode on your private RSS feed or our website at the AMA #63 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.

We discuss:

• The impact of hair loss on emotional health [2:15];
• The prevalence, patterns, and causes of hair loss in men and women [5:15];
• The genetic and hormonal causes of hair loss, and the role of dihydrotestosterone (DHT) in androgenic alopecia [8:45];
• The visual differences in hair loss patterns between men and women, and the importance of consulting a specialist to rule out non-genetic causes of hair loss [13:30];
• How genetic predisposition influences the risk of androgenic alopecia, and how early detection through diagnostic tools and blood tests can help manage risk more effectively [16:45];
• Ideal timing for starting treatment: why early treatment is crucial for effectively managing hair loss [19:30];
• The various FDA-approved treatments for androgenic alopecia, their mechanisms, and additional off-label treatments commonly used to manage hair loss [24:30];
• Topical minoxidil—the most commonly recommended starting treatment for hair loss [30:15];
• Oral vs. topical minoxidil: efficacy, ease of use, and potential side effects that must be considered [33:45];
• Finasteride for treating hair loss: efficacy, potential side effects on libido, and the need for careful PSA monitoring in men to avoid missing early signs of prostate cancer [37:15];
• Other effective hair loss treatments for women: boosting hair density with spironolactone gel and ketoconazole shampoo as part of a comprehensive strategy [41:30];
• Low-level laser therapy: effectiveness, costs, practicality, and a comparison of in-office treatments with at-home devices [49:00];
• Platelet-rich plasma (PRP) as a treatment for hair loss: potential effectiveness, varying protocols, and significant costs [53:45];
• Hair transplant for advanced hair loss: criteria and considerations [58:00];
• Types of hair transplants: follicular unit transplantation (FUT) vs. follicular unit extraction (FUE) [1:02:00];
• The financial cost of hair transplant surgery, and what to consider when seeking affordable options [1:06:15];
• The potential risks and downsides of the various hair transplant procedures [1:09:30];
• Post-procedure care for hair transplants and whether the procedure must be repeated periodically [1:16:30];
• Combining different hair loss treatments: benefits, risks, and considerations [1:18:30];
• Emerging hair loss treatments with limited data [1:21:00];
• Key considerations for selecting the right treatment plan for hair loss [1:22:00];
• A summary of the different considerations for men and women facing hair loss [1:24:30];
• Practical advice on selecting the right specialist or treatment team [1:26:15]; and
• More.

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In this episode, former World Series of Poker champion and author Annie Duke explains how poker is a pertinent model system for decision-making in the real world, a system which blends imperfect information with some unknown percentage of both luck and skill. Annie breaks down the decision-making matrix, revealing how we often focus too narrowly on just one of the four quadrants, missing out on valuable learning opportunities in the remaining 75% of situations. She delves into how our tendency to evaluate only negative outcomes leads to a culture of risk aversion. This mindset, she argues, stifles the kind of bold decision-making necessary for progress and innovation across various fields, from poker and sports to business and medicine. Annie also introduces a robust framework for learning and the levels of thought required to excel in any domain. Finally, she discusses a strategy called “backcasting”, a concept that resonated deeply with Peter in terms of how he thinks about extending healthspan.

We discuss:

• Annie’s background, favorite sports teams, and Peter’s affinity for Bill Belichick [1:30];
• Chess vs. poker: Which is a better metaphor for decision-making in life (and medicine)? [6:45];
• Thinking probabilistically: Why we aren’t wired that way, and how you can improve it for better decision-making [12:30];
• Variable reinforcement: The psychological draw of poker that keeps people playing [19:15];
• The role of luck and skill in poker (and other sports), and the difference between looking at the short run vs. long run [32:15];
• A brief explanation of Texas hold ‘em [41:00];
• The added complexity of reading the behavior of others players in poker [47:30];
• Why Annie likes to “quit fast,” and why poker is still popular despite the power of loss aversion [52:45];
• Limit vs. no-limit poker, and how the game has changed with growing popularity [55:15];
• The advent of analytics to poker, and why Annie would get crushed against today’s professionals [1:04:45];
• The decision matrix, and the “resulting” heuristic: The simplifier we use to judge the quality of decisions —The Pete Carroll Superbowl play call example [1:10:30];
• The personal and societal consequences of avoiding bad outcomes [1:21:45];
• Poker as a model system for life [1:31:30];
• How many leaders are making (and encouraging) status-quo decisions, and how Bill Belichick’s decision-making changed after winning two Super Bowls [1:35:15];
• What did we learn about decision-making from the Y2K nothingburger? And how about the D-Day invasion? [1:39:30];
• The first step to becoming a good decision maker [1:43:00];
• The difference between elite poker players and the ones who make much slower progress [1:49:45];
• Framework for learning a skill, the four levels of thought, and why we hate digging into our victories to see what happened [1:52:15];
• The capacity for self-deception, and when it is MOST important to apply four-level thinking [2:00:30];
• Soft landings: The challenge of high-level thinking where there is subtle feedback and wider skill gaps [2:11:00];
• The benefits of “backcasting” (and doing pre-mortems) [2:13:30];
• Parting advice from Annie for those feeling overwhelmed (and two book recommendations) [2:21:30]; and
• More.

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Sebastian Junger is an award-winning journalist, bestselling author, and previous guest on The Drive. In this episode, Sebastian returns to discuss his latest book, In My Time of Dying: How I Came Face to Face with the Idea of an Afterlife. This episode delves into Sebastian's profound near-death experience and how it became the catalyst for his exploration of mortality, the afterlife, and the mysteries of the universe. They discuss the secular meaning of what it means to be sacred, the intersection of physics and philosophy, and how our beliefs shape our approach to life and death. He also shares how this experience has profoundly changed him, giving him a renewed perspective on life—one filled with awe, gratitude, deeper emotional awareness, and a more engaged approach to living.

We discuss:

• How Sebastian’s near-death experience shaped his thinking about mortality and gave him a reverence for life [3:00];
• The aneurysm that led to Sebastian’s near-death experience [6:30];
• Emergency room response, his subsequent reflections on the event, and the critical decisions made by the medical team [16:30];
• Sebastian’s reaction to first learning he nearly died, and the extraordinary skill of the medical team that save his life [26:00];
• Sebastian’s near-death experience [37:00];
• The psychological impact of surviving against overwhelming odds [48:00];
• Ignored warning signs: abdominal pain and a foreshadowing dream before the aneurysm rupture [54:30];
• Sebastian's recovery, his exploration of near-death experiences, and the psychological turmoil he faced as he questioned the reality of his survival [58:15];
• A transformative encounter with a nurse who encouraged Sebastian to view his near-death experience as sacred [1:03:30];
• How Sebastian has changed: a journey toward emotional awareness and fully engaging with life [1:08:45];
• The possibility of an afterlife, and how quantum mechanics challenges our understanding of existence [1:15:15];
• Quantum paradoxes leading to philosophical questions about the nature of reality, existence after death, and whether complete knowledge could be destructive [1:26:00];
• The sweet spot of uncertainty: exploring belief in God, post-death existence, and meaning in life [1:37:00];
• The transformative power of experiencing life with awe and gratitude [1:53:00]; and
• More.

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David Allison, a leading expert in obesity and nutrition, quantitative genetics, clinical trials, and research methodology, returns to The Drive to explore the evolving landscape of nutrition science and obesity treatment. In this episode, David begins by discussing the intricate relationship between nutrition, obesity, and body composition, emphasizing the multifaceted impacts of food beyond mere calorie intake. David provides a critical analysis of the complexities in nutrition research and their practical implications for tackling obesity. He critiques historical public health policies, addresses the trust issues plaguing nutrition science, and underscores the need for a paradigm shift to more effectively combat obesity. The conversation also delves into the rise of GLP-1 receptor agonists like Ozempic and Mounjaro, exploring their ethical and practical considerations in obesity treatment. The episode concludes with an in-depth look at protein intake recommendations and highlights the significant research gaps that remain in the field.

We discuss:

• The complex relationship between nutrition, body weight, and body composition [2:30];
• The slow progress in addressing obesity and public health despite substantial effort and investment [7:30];
• The very limited success of public health initiatives in curbing obesity [17:15];
• The evolving landscape of obesity research: public health initiatives and the impact of pharmacological success [26:30];
• Rethinking obesity solutions: the need for a paradigm shift [32:45];
• Understanding environmental triggers and embracing a balanced approach to addressing obesity that includes both pharmacological treatments and realistic lifestyle changes [41:45];
• The need for higher standards in obesity research [51:45];
• The rapid success of GLP-1 receptor agonists for weight loss: a discussion on the societal impact and controversy of their growing usage [1:02:15];
• The ethical and practical considerations of obesity drugs: risks, benefits, and motivations for usage [1:11:30];
• The use of GLP-1 agonists by athletes as performance enhancers [1:23:45];
• Unanswered questions about protein intake and health [1:30:45];
• Future research needed to understand basic questions around protein intake [1:45:00];
• David’s weekly newsletter: “Obesity and Energetics Offerings” [1:50:45]; and
• More.

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In this “Ask Me Anything” (AMA) episode, Peter dives into two important health topics: uric acid and protein, examining them from unique perspectives. For uric acid, he explores its metabolic role and connection to various diseases, focusing on the potential causal link with cardiovascular disease. He also discusses factors influencing uric acid levels, such as diet, genetics, and lifestyle, providing practical tips for effective management. Shifting to protein, Peter delves into its role in appetite and weight management, the consequences of insufficient protein, and the “protein leverage hypothesis” linking protein deficiency to obesity. He covers optimal protein intake and its impact on energy expenditure, and he compares the satiety effects of solid versus liquid protein. Finally, Peter shares his strategy for incorporating protein into a comprehensive weight management plan.

If you’re not a subscriber and are listening on a podcast player, you’ll only be able to hear a preview of the AMA. If you’re a subscriber, you can now listen to this full episode on your private RSS feed or our website at the AMA #62 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.

We discuss:

• Overview of episode topics (and an important discussion on fanny packs) [2:00];
• Understanding uric acid: its role in metabolic processes, its association with gout and kidney stones, its impact on blood pressure, and more [6:00];
• Non-modifiable factors that influence uric acid levels [11:00];
• Modifiable factors that influence uric acid levels [14:15];
• Association between high uric acid levels and cardiovascular disease [20:00];
• Evidence suggesting a causal link between high uric acid levels and cardiovascular disease [24:00];
• Inconclusive evidence about the cardiovascular benefits of lowering uric acid pharmacologically [28:15];
• Exploring the potential risks of low uric acid levels in neurodegenerative diseases [37:00];
• Managing uric acid levels: dietary interventions and pharmacological approaches [42:00];
• The impact of protein on appetite and weight management [44:00];
• The consequences of insufficient protein on eating behaviors and satiety [52:15];
• The relationship between protein deficiency and obesity: exploring the “protein leverage hypothesis” [57:15];
• The impact of protein intake on energy expenditure [1:02:15];
• Determining optimal protein intake to avoid deficiency and support health [1:05:45];
• The role of different amino acids and protein sources in promoting satiety [1:08:15];
• Comparing the satiety effects of solid vs. liquid protein sources [1:10:30];
• Peter’s framework for incorporating protein intake into a strategy for controlling body weight [1:12:00]; and
• More.

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George A. Brooks is a renowned professor of integrative biology at UC Berkeley. Known for his groundbreaking "lactate shuttle" theory proposed in the 1980s, George revolutionized our understanding of lactate as a crucial fuel source rather than just a byproduct of exercise. In this episode, George clarifies common misconceptions between lactate and lactic acid, delves into historical perspectives, and explains how lactate serves as a fuel for the brain and muscles. He explores the metabolic differences in exceptional athletes and how training impacts lactate flux and utilization. Furthermore, George reveals the significance of lactate in type 2 diabetes, cancer, and brain injuries, highlighting its therapeutic potential. This in-depth conversation discusses everything from the fundamentals of metabolism to the latest research on lactate's role in gene expression and therapeutic applications.

We discuss:

• Our historical understanding of lactate and muscle metabolism: early misconceptions and key discoveries [3:30];
• Fundamentals of metabolism: how glucose is metabolized to produce ATP and fuel our bodies [16:15];
• The critical role of lactate in energy production within muscles [24:00];
• Lactate as a preferred fuel during high-energy demands: impact on fat oxidation, implications for type 2 diabetes, and more [30:45];
• How the infusion of lactate could aid recovery from traumatic brain injuries (TBI) [43:00];
• The effects of exercise-induced lactate [49:30];
• Metabolic differences between highly-trained athletes and insulin-resistant individuals [52:00];
• How training enhances lactate utilization and facilitates lactate shuttling between fast-twitch and slow-twitch muscle fibers [58:45];
• The growing recognition of lactate and monocarboxylate transporters (MCT) [1:06:00];
• The intricate pathways of lactate metabolism: isotope tracer studies, how exceptional athletes are able to utilize more lactate, and more [1:09:00];
• The role of lactate in cancer [1:23:15];
• The role of lactate in the pathophysiology of various diseases, and how exercise could mitigate lactate's carcinogenic effects and support brain health [1:29:45];
• George’s current research interests involving lactate [1:37:00];
• Questions that remain about lactate: role in gene expression, therapeutic potential, difference between endogenous and exogenous lactate, and more [1:50:45]; and
• More.

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In this special episode, Peter provides a comprehensive introduction to longevity, perfect for newcomers or those looking to refresh their knowledge. He lays out the foundational concepts of lifespan, healthspan, and the marginal decade. Additionally, Peter discusses the four main causes of death and their prevention, as well as detailing the five key strategies in his longevity toolkit to improve lifespan and healthspan. Detailed show notes provide links for deeper exploration of these topics, making it an ideal starting point for anyone interested in understanding and improving their longevity.

We discuss:

• Key points about starting exercise as an older adult [2:45];
• Overview of episode topics and structure [1:45];
• How Peter defines longevity [3:45];
• Why healthspan is a crucial component of longevity [11:15];
• The evolution of medicine from medicine 1.0 to 2.0, and the emergence of medicine 3.0 [15:30];
• Overview of atherosclerotic diseases: the 3 pathways of ASCVD, preventative measures, and the impact of metabolic health [26:00];
• Cancer: genetic and environmental factors, treatment options, and the importance of early and aggressive screening [33:15];
• Neurodegenerative diseases: causes, prevention, and the role of genetics and metabolic health [39:30];
• The spectrum of metabolic diseases [43:15];
• Why it’s never too late to start thinking about longevity [44:15];
• The 5 components of the longevity toolkit [46:30];
• Peter’s framework for exercise—The Centenarian Decathlon [47:45];
• Peter’s nutritional framework: energy balance, protein intake, and more [58:45];
• Sleep: the vital role of sleep in longevity, and how to improve sleep habits [1:08:30];
• Drugs and supplements: Peter’s framework for thinking about drugs and supplements as tools for enhancing longevity [1:13:30];
• Why emotional health is a key component of longevity [1:17:00];
• Advice for newcomers on where to start on their longevity journey [1:19:30]; and
• More.

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