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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.

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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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