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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 his discussions on diverse topics such as dopamine and addiction with Anna Lembke, the current state and exciting future of CRISPR-mediated gene editing with Feng Zhang, how to build and maintain strong bones from youth to old age with Belinda Beck, how calorie restriction may influence longevity and metabolic health with Eric Ravussin, and the role of testosterone and TRT in prostate cancer with Ted Schaeffer. 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 #325 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.

We discuss:

• Overview of topics to be covered [1:45];
• Anna Lembke episode: addiction, dopamine's role in pleasure and pain, and managing addictive behaviors [4:15];
• Follow-up questions about addiction: heritability, cold therapy, exercise, and strategies for breaking addictive behaviors [14:45];
• Feng Zhang episode: the potential of gene editing with CRISPR technology for treating diseases, and the challenges ahead [21:00];
• Feng Zhang’s impactful education experience, and how early exposure and curiosity-driven learning can develop scientific interest for kids [28:30];
• The future of CRISPR: weighing the scientific potential to combat complex diseases against ethical considerations around genetic modification [33:45];
• Belinda Beck episode: how to build and maintain strong bones from youth to old age [37:30];
• How both nutrition and exercise are crucial for bone health at all ages, and why it’s never too late to start [54:45];
• Eric Ravussin episode: calorie restriction, energy expenditure, exercise for weight maintenance, and more [59:00];
• Measuring energy intake and energy expenditure: techniques and challenges [1:09:45];
• ed Schaeffer episode: the nuance role of testosterone in prostate cancer, TRT, and the need for better cancer biomarkers [1:14:30];
• Peter’s favorite bands [1:25:45]; and
• More.

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Eric Ravussin is a world-renowned expert on obesity, metabolism, and aging whose pioneering research has shaped much of what we understand today about energy balance and caloric restriction. In this episode, Eric shares insights from his cutting-edge work on energy expenditure—a critical factor in understanding how our bodies regulate weight and appetite. He discusses methods for measuring energy output, energy balance, food intake, and appetite regulation, and explores key studies on macronutrient manipulation. Eric then delves into the CALERIE study on caloric restriction, highlighting insights related to biomarkers of both primary and secondary aging. The conversation also covers the potential of GLP-1 agonists to replicate these effects and looks ahead to how AI and technology could transform metabolic research in the coming years.

We discuss:

• Eric’s background and current work metabolism and measuring energy expenditure [3:00];
• The science behind metabolic chambers for measuring energy expenditure, and the complexities of indirect and direct calorimetry [8:00];
• The body's regulatory systems for maintaining energy balance and the primary influence of energy intake on body weight [18:30];
• The epidemic of obesity and a discussion of resting metabolic rate [24:45];
• The impact of exercise, appetite, gut hormones, and eating patterns on weight regulation [28:45];
• Experiments looking at how macronutrient composition affects energy expenditure [38:45];
• The challenges of studying diet in real-life settings, the potential of personalized nutrition, and how public health policy could play a role in guiding nutritional habits [51:00];
• The importance of protein in the diet, the limitations of dietary data collection, and how AI could potentially transform nutrition science [1:08:15];
• How Eric’s interest in caloric restriction (CR) began with Biosphere 2, metabolic efficiency's role in aging, and goals of the CALERIE study [1:15:15];
• The CALERIE study: exploring the real-world impact of caloric restriction [1:28:00];
• Notable findings from the CALERIE study after two years: sustained weight loss, participant retention, and more [1:40:00];
• The effect of caloric restriction on the hallmarks of aging [1:47:00];
• The challenge of applying CR to the general population, the potential of drugs and exercise to mimic the effects of CR [1:55:45];
• Upcoming study comparing caloric restriction to time-restricting eating, and Peter’s takeaways from the discussion [2:02:45]; and
• More.

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Feng Zhang, a professor of neuroscience at MIT and a pioneering figure in gene editing, joins Peter to discuss his groundbreaking work in CRISPR technology, as well as his early contributions to optogenetics. In this episode, they explore the origins of CRISPR and the revolutionary advancements that have transformed the field of gene editing. Feng delves into the practical applications of CRISPR for treating genetic diseases, the importance of delivery methods, and the current successes and challenges in targeting cells specific tissues such as those in the liver and eye. He also covers the ethical implications of gene editing, including the debate around germline modification, as well as reflections on Feng’s personal journey, the impact of mentorship, and the future potential of genetic medicine.

We discuss:

• Feng’s background, experience in developing optogenetics, and his shift toward improving gene-editing technologies [2:45];
• The discovery of CRISPR in bacterial DNA and the realization that these sequences could be harnessed for gene editing [10:45];
• How the CRISPR system fights off viral infections and the role of the Cas9 enzyme and PAM sequence [21:00];
• The limitations of earlier gene-editing technologies prior to CRISPR [28:15];
• How CRISPR revolutionized the field of gene editing, potential applications, and ongoing challenges [36:45];
• CRISPR’s potential in treating genetic diseases and the challenges of effective delivery [48:00];
• How CRISPR is used to treat sickle cell anemia [53:15];
• Gene editing with base editing, the role of AI in protein engineering, and challenges of delivery to the right cells [1:00:15];
• How CRISPR is advancing scientific research by fast-tracking the development of transgenic mice [1:06:45];
• Advantages of Cas13’s ability to direct CRISPR to cleave RNA and the advances and remaining challenges of delivery [1:11:00];
• CRISPR-Cas9: therapeutic applications in the liver and the eye [1:19:45];
• The ethical implications of gene editing, the debate around germline modification, regulation, and more [1:30:45];
• Genetic engineering to enhance human traits: challenges, trade-offs, and ethical concerns [1:40:45];
• Feng’s early life, the influence of the American education system, and the critical role teachers played in shaping his desire to explore gene-editing technology [1:46:00];
• Feng’s optimism about the trajectory of science [1:58:15]; and
• More.

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Belinda Beck, founder of The Bone Clinic and a leading authority on exercise physiology and bone health, delves into the science of osteoporosis, bone density, and the lifelong importance of maintaining skeletal health. In this episode, she explains how the foundation for strong bones is established during childhood, offering valuable advice for parents on optimizing bone health for their kids. She also explores how bone remodeling occurs throughout life, driven by activity, nutrition, and hormones. Belinda highlights the power of resistance training in improving bone strength, even for those at risk of bone loss, and emphasizes the role of essential vitamins and minerals in maintaining bone health. She shares practical strategies, backed by research, for preventing fractures and combating osteoporosis.

We discuss:

• Belinda’s journey into bone health research and training [2:45];
• The physiology of bone and how bones adapt to mechanical loading [8:15];
• Bone development from birth to adulthood, why early life is a crucial period, the functions of osteoblasts and osteoclasts, and gender differences in BMD [14:00];
• How parents can optimize their children’s bone health through diet (calcium and vitamin D), sunlight exposure, and physical activity [27:30];
• The best sports and activities for promoting bone health, weight training for kids, and advice for parents [36:30];
• The impact of corticosteroid use on bone health in children and strategies to minimize negative effects [48:30];
• Advice for people in middle age to preserve bone density: physical activity and bone-loading exercises [52:00];
• Bone loss during the menopause transition for women: hormone replacement therapy and other strategies to mitigate BMD losses [59:30];
• Interpreting the bone mineral density results from a DEXA scan: T-score, Z-score, and more [1:03:00];
• The LIFTMOR study: testing the effects of heavy weightlifting on bone health in postmenopausal women with low bone density [1:10:15];
• Profound benefits of weight training outside of BMD improvements: exploring the broader impacts on patients in the LIFTMOR study [1:19:30];
• Guidance for people wanting to use exercise designed to improve their bone health [1:29:30]; and
• More.

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Anna Lembke is the Chief of the Stanford Addiction Medicine Dual Diagnosis Clinic and author of Dopamine Nation: Finding Balance in the Age of Indulgence. In this episode, Anna dives deep into the biochemistry and neurobiology of addiction, exploring the critical role of dopamine and the prefrontal cortex. She shares her framework for diagnosing and treating addiction, providing real-world examples involving alcohol, gambling, cannabis, social media, and more. Anna outlines the risk factors for addiction, including inherited and nurture-based risks, explores the rise of addictions in younger generations, and discusses effective ways to address these issues with children. Additionally, she touches on healthy coping strategies, the evolution of the “marshmallow experiment,” and provides insights into GLP-1 agonists as a possible tool for addiction treatment. Finally, she reflects on the value of 12-step programs and how she navigates the emotional challenges of her work.

We discuss:

• The role of dopamine and the prefrontal cortex in addiction [3:00];
• The clinical definition of addiction and the behavioral criteria for diagnosing it [13:00];
• Assessing alcohol use: patterns, risks, and addiction diagnosis [17:15];
• Applying the addiction diagnosis framework using gambling as an example [21:45];
• Exploring addiction variability: how nature, nurture, and access shape individual vulnerability and drug of choice [25:15];
• How abstinence from addictive behaviors can help reset the brain’s reward system and improve mental health [41:15];
• Safely abstaining from addiction substances, drugs needing medical supervision, and other key considerations [51:30];
• Transitioning from abstinence to long-term recovery: tools and considerations [59:00];
• Exploring behavioral addictions like sex addiction, and the gender differences in addiction patterns [1:08:30];
• Factors contributing to the increasing levels of addiction across the world [1:13:45];
• How online pornography can affect young boys' developing brains and lead to addictive behaviors, and strategies for parents to address this issue [1:23:30];
• The link between social media use and declines in mental health, potential solutions, and protective measures [1:34:45];
• How exercise affects brain chemistry, the role of dopamine and endorphins, and how exercise can become addictive [1:44:00];
• Cold-water immersion for mood regulation, and other healthy coping strategies [1:47:15];
• The “marshmallow experiment”: how broken promises affect behavior and trustworthy environments help children develop self-control [1:54:00];
• Can GLP-1 agonists be useful in treating addiction? [1:58:30];
• The benefits of 12-step programs [2:06:00];
• Why understanding a patient’s story is essential for meaningful psychiatric care [2:11:45]; 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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