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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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