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Andy Galpin is a Professor of Kinesiology at California State University at Fullerton, where he studies muscle adaptation and applies his research to work with professional athletes. In this episode, Andy sets the foundation for the conversation by discussing the anatomy, microanatomy, and physiology of the muscle, including explaining what it actually means to undergo hypertrophy of the muscle. He then explains the difference between power, strength, speed, and hypertrophy and how those differences relate to what's happening at the cellular level and the functional unit level. Additionally, he discusses energy sources for muscles, the importance of protein for muscle synthesis, the various types of muscle fibers, and the factors that determine one’s makeup of muscle fibers. Finally, Andy wraps the conversation with how he would design a program for an untrained person committed to adding muscle and functional strength for longevity.

We discuss:

• Andy’s path to expertise in exercise [3:30];
• Contrasting strength, power, and force production and how they inform us about training for longevity [9:30];
• Muscle energetics: Fuels that provide energy to muscles, and the importance of protein [17:45];
• The structure and microanatomy of muscle, muscle fibers, and more [29:30];
• Energy demands of skeletal muscle compared to other tissues in the body [39:45];
• How a muscle contraction works and why it requires ATP [48:00];
• Muscle fibers: modulation between fiber types with movement and changes in fibers with training and aging [53:15];
• Andy’s study of twins demonstrating the difference in muscle fibers between a trained and untrained individual [1:02:30];
• Microanatomy of fast-twitch and slow-twitch muscle fibers [1:11:15];
• Factors that determine one’s makeup of muscle fibers and how adaptable they are with training [1:22:15];
• Hypertrophy and what happens at the cellular level when a muscle grows [1:30:00];
• How athletes quickly cut water weight and the rehydration process [1:37:30];
• Different types of athletes [1:47:30];
• Training advice for a hypothetical client who’s untrained and wants to add muscle and functional strength for longevity [1:49:45];
• Changes in muscle and muscular function that occur with aging [1:53:45];
• Training plan for the hypothetical client [1:59:30];
• What drives muscle hypertrophy? [2:12:15];
• How to properly incorporate isometric exercises into a workout [2:19:00];
• Additional training tips: movement patterns, how to finish a workout, and more [2:25:45];
• Ways to incorporate high heart rate exercise into a workout plan [2:28:45]; and
• More.

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In this “Ask Me Anything” (AMA) episode, Peter answers questions related to the leading cause of death in both men and women—atherosclerotic cardiovascular disease (ASCVD). He highlights the most important risk factors for ASCVD, such as apoB, LDL, hyperinsulinemia, and Lp(a), and explains the mechanism by which they confer risk and how these factors are interrelated. Peter also dives deep into the data around apoB to try to answer the question of how much residual risk is conferred for ASCVD through metabolic dysfunction once you correct for apoB. He also looks at the data around lifetime risk reduction of ASCVD in the context of low apoB.

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 #42 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.

We discuss:

• A racecar analogy for understanding atherosclerotic cardiovascular disease [2:00];
• Defining and differentiating apoB and LDL-C [10:00];
• The interrelated nature of insulin levels, apoB, triglycerides, and ASCVD parameters [13:00];
• Another way that hyperinsulinemia plays a role in endothelial dysfunction [18:00];
• Why Peter uses the oral glucose tolerance test (OGTT) with all patients [20:15];
• Is there any evidence that hyperinsulinemia is an independent contributor to ASCVD? [23:00];
• Thinking through risk in the context of high-fat diets resulting in improved metabolic metrics but with an elevation of apoB/LDL-C [27:30];
• Thinking through risk in the context of low apoB but higher than normal triglyceride levels [32:15];
• The importance of lowering apoB for reducing ASCVD risk [38:15];
• Data on men and women with familial hypercholesterolemia that demonstrates the direct impact of high apoB and LDL-C on ASCVD risk [47:45];
• Importance of starting prevention early, calcium scores, and explaining causality [52:30];
• Defining Lp(a), its impact on ASCVD risk, and what you should know if you have high Lp(a) [56:30];
• Lp(a) and ethnic differences in risk [1:00:30];
• Why someone with elevated Lp(a) should consider being more aggressive with apoB lowering strategies [1:05:00];
• Addressing the common feeling of hesitancy to taking a pharmacologic approach to lower ASCVD risk [1:07:15];
• Peter’s take on the 2022 Formula 1 season and thoughts on 2023 [1:15:15]; and
• More.

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Bill Perkins is one of the world’s most successful hedge fund managers and entrepreneurs, and the author of the bestseller, Die With Zero. In this episode, Bill unpacks the Die With Zero philosophy which challenges conventional thinking related to the balance between health, wealth, and time—the three variables important for fulfillment. Bill makes the case that we should strive for maximum net fulfillment rather than net worth (or even health). He argues that we need to optimize our life to have memorable experiences before it’s too late and that most people are over-saving and under-living. Bill also explains how one can apply the principles in Die With Zero to break out of “autopilot” and optimize their life to achieve maximum net fulfillment.

We discuss:

• Bill’s upbringing, background, and first job on Wall Street [3:15];
• A missed experience and feeling of regret that shaped Bill’s thinking [14:15];
• Thinking in terms of time, and the relationship between money, time, and health [17:00];
• Solving for net fulfillment and allocating your time based on the seasons of life [27:15];
• How Bill thinks about risk, opportunity costs, and the difference between fear and risk tolerance [35:30];
• Optimizing for fulfillment, finding purpose outside of work, and more [41:45];
• Thinking about the order of experiences you want to have based on seasons of life [50:00];
• Bill’s unique perspective on philanthropy and a more impactful way to give money away [54:45];
• Applying the principles in ‘Die With Zero’ to maximize fulfillment [1:04:00];
• How to break out of living life on autopilot [1:14:30];
• When should your net worth peak? [1:18:00];
• Taking calculated risks [1:21:30];
• Bill shares a lesson from his incredible birthday [1:25:15];
• How Bill’s philosophy has evolved since writing Die With Zero [1:34:00]; and
• More.

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Kellyann Niotis is a neurologist specializing in risk reduction strategies for the prevention or slowing of neurodegenerative disorders. In this episode, Kellyann provides an overview of the various diseases associated with neurodegeneration, including, but not limited to, Alzheimer’s disease, Lewy body dementia, and Parkinson’s disease. She goes in-depth on Parkinson’s disease, explaining its pathology, role in movement capacity, very early warning signs, and the role of anxiety and sleep. Similarly, she provides an in-depth discussion of Alzheimer’s disease, including the latest in screening, genetics, and tools/strategies for prevention. She ties the discussion together by explaining the differences and commonalities among the various diseases of neurodegeneration and the potential causative triggers, and she highlights the importance of early screening, cognitive testing, and taking the proper steps to lowering the risk of disease.

We discuss:

• Kellyann’s background, training, and interest in the brain [2:30];
• A primer on neurodegeneration: different types, prevalences, interventions, and more [5:30];
• Overview of Parkinson’s disease and neuromuscular disorders including ALS [16:00];
• Parkinson’s disease: early signs, diagnosis, genetics, causative triggers, and more [17:30];
• Interventions to delay or avoid Parkinson’s disease, and the role of sleep and anxiety [31:15];
• The challenge of standardizing early interventions for Parkinson’s disease without a clear biomarker [39:45];
• Alzheimer’s disease: pathophysiology and the role of the amyloid and tau proteins [47:45];
• Can PET scans be informative for diagnosing Alzheimer’s disease? [51:15];
• Tau accumulation in the brain, tau scans, serum biomarkers, and possible early detection of Alzheimer’s disease pathology [57:00];
• Cognitive testing explained [1:03:30];
• The challenge of identifying the stage of the disease and why drugs have not shown efficacy [1:14:45];
• The association between hearing loss and dementia [1:17:45];
• The relationship between oral health and neurodegenerative diseases [1:21:30];
• Genetic risk for Alzheimer’s disease [1:24:45];
• What one’s mitochondrial haplotype can reveal about their risk of neurodegenerative disease [1:32:30];
• The positive impact of exercise on brain health [1:37:00];
• High blood pressure as a risk factor [1:40:00];
• Why women are disproportionately affected by Alzheimer’s disease [1:44:15];
• Final takeaways: the future of understanding neurodegenerative disease and further reducing risk [1:46:45]; and
• More.

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James Clear is the author of the New York Times bestseller Atomic Habits. His extensive research into human behavior has helped him identify key components of habit formation and develop the “Four Laws of Behavioral Change.” In this episode, James provides insights into how both good and bad habits are formed, including the influence of genetics, environment, social circles, and more. He points to changes one can make to cultivate more perseverance and discipline and describes the profound impact habits can have when tying them into one’s self-identity. Finally, James breaks down his “Four Laws of Behavioral Change” and how to use them to create new habits, undo bad habits, and make meaningful changes in one’s life.

We discuss:

• Why James became deeply interested in habits [1:45];
• Viewing habits through an evolutionary lens [6:00];
• The power of immediate feedback for behavior change, and why we tend to repeat bad habits [9:15];
• The role of genetics and innate predispositions in determining one’s work ethic and success in a given discipline [14:30];
• How finding one’s passion can cultivate perseverance and discipline [23:15];
• Advantages of creating systems and not just setting goals [29:15];
• The power of habits combined with self-identity to induce change [36:30];
• How a big environmental change or life event can bring on radical behavioral change [50:30];
• The influence of one’s social environment on their habits [54:15];
• How and why habits are formed [1:00:30];
• How to make or break a habit with the “Four Laws of Behavior Change” [1:09:30];
• Practical tips for successful behavioral change—the best strategies when starting out [1:16:15];
• Self-forgiveness and getting back on track immediately after slipping up [1:30:30];
• Law #1: Make it obvious—Strategies for identifying and creating cues to make and break habits [1:39:45];
• Law #2: Make it attractive—examples of ways to make a new behavior more attractive [1:47:45];
• Law #3: Make it easy—the 2-minute rule [1:58:45];
• Law #4: Make it satisfying—rewards and reinforcement [2:03:30];
• Advice for helping others to make behavioral changes [2:06:00]; and
• More.

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Layne Norton holds a Ph.D. in nutritional sciences and is a physique coach, natural bodybuilder and powerlifter, and two-time previous podcast guest. In this episode, Layne discusses his training as a powerlifter and shares training principles that non-powerlifters can apply to improve muscle strength and mass. Layne goes in-depth on creatine supplementation, including the benefits for lean mass and strength, and addresses the common arguments against its regular usage. Additionally, Layne touches on many areas of nutrition, including how his opinions have changed on certain topics. Layne also touches on the subjects of protein, fiber, and fat in the diet, as well as the different tools and dietary approaches for energy restriction.

We discuss:

• The sport of powerlifting and Layne’s approach during competitions [2:30];
• Training for strength: advice for beginners and non-powerlifters [13:15];
• Low-rep training, compound movements, and more tips for the average person [23:15];
• How strength training supports longevity and quality of life: bone density, balance, and more [28:15];
• Peak capacity for strength as a person ages and variations in men and women [33:00];
• Effects of testosterone (endogenous and exogenous) on muscle gain in the short- and long-term [36:45];
• How Layne is prepping for his upcoming IPF World Masters Powerlifting competition [44:00];
• Creatine supplementation [54:30];
• How important is rep speed and time under tension? [1:05:30];
• Validity of super slow rep protocols, and the overall importance of doing any exercise [1:12:45];
• Navigating social media: advice for judging the quality of information from “experts” online [1:23:00];
• Layne’s views on low-carb diets, the tribal nature of nutrition, and the importance of being able to change opinions [1:34:45];
• Where Layne has changed his views: LDL cholesterol, branched-chain amino acid supplementation, intermittent fasting, and more [1:42:00];
• The carnivore diet, elimination diets, and fruits and vegetables [1:55:15];
• Fiber: Layne’s approach to fiber intake, sources of fiber, benefits, and more [2:00:15];
• Confusion around omega-6 polyunsaturated fatty acids and the Minnesota Coronary Experiment [2:05:00];
• Layne’s views on fats in the diet [2:13:00];
• Flexible dieting, calorie tracking, and the benefits of tracking what you eat to understand your baseline [2:18:00];
• The nutritional demands of preparing for a bodybuilding show [2:30:45];
• The psychological effects of aging and changes to one’s identity [2:42:00]; and
• More.

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Chris Hemsworth, best known for his role as Thor in the Marvel movies, joins Peter to discuss his recent work in the docuseries called Limitless. In the docuseries, Chris undertook extreme challenges to explore his physical and emotional limits and gain insights into longevity. In this episode, Chris discusses these many challenges—from fasting to arctic swims to 100-foot rope climbs—as well as the insights that he gained from each. Peter, who also played a role in the docuseries, guides Chris through the science of longevity, including what Chris’s APOE-ε4 genotype means for his risk of Alzheimer’s disease. Additionally, Chris describes how his outlook on health, happiness, work-life balance, and more have changed from his experience on Limitless.

We discuss:

• Limitless: how Chris got involved and his overall experience filming the docuseries [3:00];
• “Fasting” ‒ ep. 3 of Limitless in which Chris attempts a 4-day fast [8:15];
• “Shock” ‒ ep. 2 of Limitless in which Chris swims in the Arctic Ocean [12:15];
• Cold exposure: the potential physical and mental benefits [19:30];
• “Strength” ‒ ep. 4 of Limitless in which Chris explores how muscle can improve longevity [21:15];
• The APOE-ε4 genotype and Alzheimer’s disease risk [31:30];
• How Chris uses sauna [39:45];
• “Acceptance” - ep. 6 of Limitless in which Chris explores the meaning of life by contemplating death [42:15];
• Chris’s new perspective on work-life balance [52:00];
• “Stress-Proof” - ep. 1 of Limitless in which Chris learns about the impact of stress and how to manage it [54:30];
• Chris reflects on his intrinsic motivation driven by both fear and purpose [58:00];
• Chris reflects on his career arc and how his presence as an actor has evolved [1:01:15];
• How Chris’s outlook has changed since filming Limitless [1:05:00]; and
• More.

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In this “Ask Me Anything” (AMA) episode, Peter answers a number of questions on optimizing sleep. He describes his pre-bedtime routine, how he utilizes a sauna, and his current regimen of medicines and supplements for improving sleep time and quality. He goes in depth on each of the molecules that have shown promise in boosting sleep, including their mechanisms of action as well as any noteworthy contraindications. Peter also discusses sleep wearables, including both the positives and potential negatives of using such trackers, and much more.

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 on our website at the AMA #42 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.

We discuss:

• Peter’s current pre-bedtime routine [3:30];
• Sauna: Peter’s routine, sleep benefits, and tradeoffs [10:45];
• Importance of keeping an open mind as new information arrives [16:15];
• Importance of reducing stimulation leading up to bedtime [19:30];
• Medications that can enhance sleep: mechanisms of action, contraindications, risks, and Peter’s regimen [20:30];
• Why medications can enhance sleep, but should not replace good sleep habits [34:45];
• Sleep supplements: mechanisms of action, contraindications, and Peter’s regimen [37:30];
• Temperature during sleep, cooling devices, mattresses, and more [53:00];
• A tip to help avoid straining your back in the morning [59:15];
• Contrasting polysomnography with wearable sleep trackers [1:00:45];
• Sleep tracking wearables: interpreting metrics, and the pros and cons of trackers [1:04:30];
• Final takeaways on sleep [1:16:30]; and
• More.

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Alton Barron is an orthopedic surgeon specializing in the shoulder, elbow, and hand. In this episode, Alton breaks down the anatomy of the upper extremities and discusses the most common injuries associated with this area of the body. He explains in detail how he examines the shoulder, elbow, and hand to find the source of the pain and lays out the non-surgical and surgical treatment options as well as the factors that determine whether surgery is appropriate. Additionally, Alton describes the surgical procedures that, when done appropriately, can lead to tremendous reduction of pain and improvement in function.

We discuss:

• Alton’s path to orthopedic surgery [3:45];
• Evolution of orthopedics and recent advances [8:45];
• Anatomy of the upper extremities [13:30];
• Rotator cuff injuries, shoulder joint dislocation, and more [21:15];
• Peter’s shoulder problems [31:30];
• The structure of the biceps and common injuries [35:30];
• Labrum tears in the shoulder and natural loss of cartilage with usage and time [38:15];
• Shoulder evaluation with MRI vs. physical exam, diagnosing pain, and when to have surgery [41:30];
• How anatomical variation can predispose one to injury and how screening may help [50:30];
• Pain generators in the shoulder, and the important nuance of the physical exam [56:00];
• Frozen shoulder [1:05:15];
• Shoulder pain that originates in the neck [1:11:15];
• Surgical treatments for a labral tear, and factors that determine whether surgery is appropriate [1:16:00];
• Repairing the rotator cuff [1:29:15];
• Are platelet-rich plasma (PRP) injections or stem cells beneficial for healing tears? [1:38:15];
• Repair of an AC joint separation [1:45:15];
• Total shoulder replacement [1:55:45];
• The elbow: anatomy, pain points, common injuries, treatments, and more [2:05:30];
• How Tommy John surgery revolutionized Major League Baseball [2:17:15];
• History of hand surgery and the most significant advancements [2:22:15];
• The hand: anatomy, common injuries, and surgeries of the hand and wrist [2:29:30];
• Carpal tunnel syndrome [2:40:00];
• Other common injuries of the hand and forearm [2:47:15];
• Grip strength [2:55:15];
• Arthritis in the hands [2:59:30];
• Trigger finger [3:07:45];
• Nerve pain, numbness, and weakness in the upper limbs [3:14:00];
• The Musician Treatment Foundation [3:22:00];
• Gratitude and rucking [3:34:15]; and
• More.

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Gerald Shulman is a Professor of Medicine, Cellular & Molecular Physiology, and the Director of the Diabetes Research Center at Yale. His pioneering work on the use of advanced technologies to analyze metabolic flux within cells has greatly contributed to the understanding of insulin resistance and type 2 diabetes. In this episode, Gerald clarifies what insulin resistance means as it relates to the muscle and the liver, and the evolutionary reason for its existence. He goes into depth on mechanisms that lead to and resolve insulin resistance, like the role of diet, exercise, and pharmacological agents. As a bonus, Gerald concludes with insights into Metformin’s mechanism of action and its suitability as a longevity agent.

We discuss:

• Gerald’s background and interest in metabolism and insulin resistance (2:30);
• Insulin resistance as a root cause of chronic disease (6:30);
• How Gerald uses NMR to see inside cells (10:00);
• Defining and diagnosing insulin resistance and type 2 diabetes (17:15);
• The role of lipids in insulin resistance (29:15);
• Confirmation of glucose transport as the root problem in lipid-induced insulin resistance (38:15);
• The role of exercise in protecting against insulin resistance and fatty liver (48:00);
• Insulin resistance in the liver (1:05:00);
• The evolutionary explanation for insulin resistance—an important tool for surviving starvation (1:15:15);
• The critical role of gluconeogenesis, and how it’s regulated by insulin (1:20:30);
• Inflammation and body fat as contributing factors to insulin resistance (1:30:15);
• Treatment approaches for fatty liver and insulin resistance, and an exciting new pharmacological approach (1:39:15);
• Metformin’s mechanism of action and its suitability as a longevity agent (1:56:15); and
• More.

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