View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter Ethan Weiss is a preventative cardiologist at UCSF, an entrepreneur-in-residence at Third Rock Ventures, where he is working on a project related to cardiometabolic disease, and a previous guest on The Drive. In this episode, Ethan compares and contrasts the diagnostic imaging tools, CAC (coronary artery calcium score) and CTA (CT angiography), used to image plaque—including the latest in CTA software—and how these tools inform our understanding of ASCVD risk and guide clinical decision-making. Ethan discusses the types of plaque that cause events and the data that make a case for optimal medical therapy over stenting outside of particular cases. He explains why high blood pressure is problematic and walks through the data from clinical trials testing aggressive treatment. He talks about the best way to actually measure blood pressure, why we shouldn’t simply accept that blood pressure rises with age, and how he uses different pharmaceutical agents to treat hypertension. Additionally, Ethan explains our current, but limited, understanding of the role of metabolic health in ASCVD. He discusses the impact of fat storage capacity and the location of fat storage and explains how and why there is still a residual risk, even in people who have seemingly normal lipids, don't smoke, and have normal blood pressure. We discuss: Ethan’s entrepreneurial work in the cardiometabolic disease space [4:30]; Calcium scans (CAC scores) and CT angiography (CTA), and how it informs us about ASCVD risk [6:00]; Peter’s historical CAC scores, CTA results, and how one can be misled [10:45]; How Peter’s CTA results prompted him to lower his apoB [14:45]; Calcium scans vs. CT angiogram (CTA) [21:15]; How Ethan makes clinical decisions based on CTA results and plaque burden, and the importance of starting treatment early to prevent ASCVD [28:15]; Improved methods of CTA to grade plaque lesions and how it’s shaped medical decisions such as stenting [33:45]; Why Ethan favors optimal medical therapy over stenting outside of particular situations [41:45]; The need for FFR CTA, and the potential for medical therapy to eliminate ASCVD [54:00]; The fat attenuation index (FAI) and other ways to measure inflammation in a plaque [57:30]; Statins and exercise may increase the risk of calcification, but what does this mean for risk? [59:45]; The root cause of statin hesitation despite evidence that statins are a profoundly important intervention [1:05:30]; Importance of keeping blood pressure in check, defining what’s normal, and whether we should just accept higher blood pressure with age [1:10:45]; Blood pressure variability, how to best measure it, and data suggesting the enormous impact of keeping blood pressure down [1:21:00]; Drugs for treating high blood pressure recommended by the ALLHAT trial [1:35:15]; What the SPRINT trial says about the aggressive treatment of hypertension, and the risks of such treatment [1:38:15]; Confirmatory results in the STEP trial for blood pressure, and how Ethan uses the various pharmacological agents to lower blood pressure in patients [1:43:15]; The role metabolic health in ASCVD: what we do and don’t know [1:51:00]; The impact of fat storage capacity and the location of fat storage on metabolic health and coronary artery disease [1:56:15]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter In this “Ask Me Anything” (AMA) episode, Peter focuses the discussion on two topics getting a lot of attention recently. He first dives deep into GLP-1 agonists, most notably semaglutide and tirzepatide, which originally came to market as diabetes drugs but are now being studied and prescribed for weight loss. He walks through the data and compares the effectiveness of the two drugs, the side effects, and perhaps more importantly, his reservations around wide use of these drugs and who he would consider to be a candidate for them. Next, Peter discusses how metformin, another drug originally brought to market for diabetes management, gained popularity as a potential longevity drug even for non-diabetics. Peter gives his take on this possibility and reviews data from a more recent study investigating the question of whether metformin should be used for general “geroprotection.” 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 #45 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here. We discuss: The hype around semaglutide, tirzepatide, and other GLP-1 agonists for weight loss [2:30]; Overview of GLP-1 agonists and why these drugs are getting so much attention [6:15]; Defining the term “geroprotective” [13:30]; Semaglutide: background, brand names, indications, and more [15:15]; Tirzepatide: background, brand names, indications, and more [19:15]; How semaglutide and tirzepatide compare in their efficacy in terms of weight loss and other metabolic health metrics [23:45]; Data showing sustained weight loss and improved metabolic metrics with after more than a year of using semaglutide and tirzepatide [29:00]; What happens to body weight when a patient discontinues the medication? [34:45]; Noteworthy side effects of GLP-1 agonists and similar classes of drugs [40:45]; Increased resting heart rate and other concerning trends in patients using GLP-1 agonists [45:15]; Changes in body composition (body fat and lean muscle) in patients on GLP-1 agonists [50:45]; Possible reasons for the loss of lean muscle mass and tips for protecting lean mass [59:00]; GLP-1 agonists and thyroid cancer [1:01:30]; Who might be a candidate for GLP-1 agonists? [1:03:45]; The large financial cost of this class of drugs [1:08:30]; Metformin as a geroprotective drug: origin of the idea that metformin could be a longevity agent even for non-diabetic patients [1:11:30]; A 2022 study on metformin sheds more light on the question of whether metformin should be used for “geroprotection” in non-diabetics [1:21:00]; Peter’s current approach with metformin for his patients [1:25:15]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter Lewis Howes is a New York Times best-selling author, entrepreneur, speaker, and host of the popular podcast, The School of Greatness. In this episode, Lewis opens up about the various hardships and traumatic events he experienced starting at a very young age and reveals the valuable lessons he learned as he worked through those traumas to improve his emotional health. He talks about how his past hardships likely contributed to his success in business and athletics, only to leave him feeling unsatisfied and unfulfilled. Next, he discusses how many aspects of his life were suffering, the inflection point that drove Lewis to seek help, and the long but beautiful healing journey that followed. Lewis makes the case that adversity, and even trauma, can be beneficial if one finds meaning in tribulations and has the courage to face one’s fears and insecurities. Finally, Lewis shares the many modalities of therapy that helped him along the way and gives advice for those wanting to find inner peace and live a fulfilling, rich, abundant, joyful life. We discuss: Lewis’s upbringing and the impact of his older brother going to prison [2:45]; Finding lessons in tragedy and adversity [10:45]; Lasting trauma from being sexually abused at age 5 [13:15]; Inflection point that drove Lewis to seek help, and a beautiful experience at a therapeutic workshop [16:45]; A powerful workshop on emotional intelligence jump started Lewis’s healing journey [27:30]; How being authentic can strengthen bonds with family and bring inner peace [39:30]; Comparing adversity with trauma and finding meaning in struggle [45:15]; Association between adverse childhood events and diseases in adulthood [56:15]; How addressing his issues with intimate relationships helped Lewis overcome physical pain related to his past trauma [59:15]; Healing is a journey that takes time and requires courage to face your fears and insecurities [1:08:45]; How Lewis thinks about mortality and uses it as motivation to pursue his dreams [1:13:00]; How anyone can benefit from therapy or coaching, and Lewis’s advice for finding inner peace [1:22:45]; Lewis’s newest book, The Greatness Mindset [1:29:15]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter Siddhartha Mukherjee is an oncologist, Pulitzer Prize-winning author, and previous guest on The Drive. In this episode, Sid discusses many of the subjects of his latest book, The Song of the Cell, including the incredible discovery of the cell and how it transformed medicine. He explains the evolutionary drive to go from single-cell to multicellular life and unpacks the four different types of cell-based therapies and the problems they are attempting to solve. He also provides the latest in gene therapy, such as CRISPR, and the ethical questions around human gene editing. Additionally, he touches on a number of fascinating topics, such as the challenges of medical science, the human brain, learning styles, his writing process, mental health, and more. We discuss: How the cell brings the genome to life, and how Sid’s recent book fits into his prior work to tell a story [2:30]; How the germ theory of disease and an understanding of the cell fueled a big leap in medicine [9:45]; What is the evolutionary drive for multicellular life? [17:15]; Four types of cell therapies and the challenges of gene therapy [26:00]; CAR T-cell therapy: promising gene therapy for cancer [36:30]; The possibility of using gene therapy to treat germline mutations like sickle cell disease [41:45]; The incredible revolution of gene editing with CRISPR [45:15]; Ethical questions around human gene editing [52:30]; The complex role of genetics in mental illness [1:01:30]; Two types of problems in science: the “eye in the sandstorm” problem and the “sand in the eye” problem [1:06:15]; Understanding neural networks: an example of the “sand in the eye” problem being solved [1:08:45]; Importance of learning by doing: comparing the learning styles of a doctoral student to a medical student [1:16:30]; Sid’s unique and brilliant style of writing [1:20:45]; Falling as the leading cause of accidental death: a liability of multicellular existence [1:25:00]; Sid’s struggle with depression and his desire to change the stigma around mental illness [1:29:15]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter Anthony Hipolito is a sheriff’s deputy in Hays County, Texas with over 24 years of experience in law enforcement. In this episode, Anthony discusses his work to spread awareness about illicit fentanyl use and the drastic increase in accidental overdoses, especially in young people. Anthony explains the deadly nature of fentanyl, including how many counterfeit drugs are now being laced with deadly doses of fentanyl. He breaks down how fentanyl is being brought to the US and how younger and younger kids are being targeted. Additionally, Anthony discusses his goal of spreading awareness to our communities and provides important advice for what parents can do. We discuss: Anthony’s life of service in law enforcement [5:30]; Fentanyl: medical use, recreational use, and the recent rise in prevalence [8:30]; The story of a teenager dying from an accidental overdose of fentanyl [16:30]; The scope of deaths being caused by accidental overdoses (the majority of which are from fentanyl) [23:00]; How young kids are being targeted, and how fentanyl makes it across our borders and gets distributed [28:30]; What happens to a person when they overdose [35:30]; Whether laws around drug possession are helping or hurting, and the need to focus on helping people that feel the need to take these counterfeit drugs [37:00]; How fentanyl is being added to all kinds of drugs that you wouldn’t expect [42:45]; What can we do as parents? [47:15]; Narcan: a treatment for opioid overdoses [50:15]; Importance of awareness, having conversations with kids early in life, and other key takeaways for parents [56:30]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter In this “Ask Me Anything” (AMA) episode, Peter reviews the last 12+ years of his DEXA scan results revealing the changes to his body composition, lean muscle mass, visceral adipose tissue, and more. He explains how his body composition and blood biomarkers were impacted by the various dietary approaches (ketosis, fasting, high protein, etc.) and training protocols (primarily endurance, primarily strength training, etc.) he has undertaken over the years. Furthermore, Peter explains his planned approach moving forward following his most recent DEXA scan in late 2022. 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 #44 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here. We discuss: DEXA scans and other methods for tracking body composition [2:30]; Importance of tracking data over time to see trends [10:15]; DEXA scans in 2011: swimming, lifting, and a carb-restricted diet [12:45]; DEXA scans 2012-2014 during Peter’s time on a strict ketogenic diet [18:30]; Blood biomarkers for evaluating metabolic health [25:15]; DEXA scan in 2020 after several years of regularly engaging in time-restricted feeding and prolonged fasting protocols [28:45]; DEXA scan in 2021: shifting focus to adding muscle, high-protein diet, and more strength training [40:00]; DEXA scan in early 2022: eating additional calories and adding blood flow restriction (BFR) to his workouts [44:45]; DEXA scan in late 2022: a dramatic change following shoulder surgery, and the impact of stress [48:30]; Peter’s approach moving forward following his most recent DEXA scan [59:15]; A rundown of the various nutritional methods of energy restriction [1:06:15]; Current thoughts on fasting and key takeaways [1:09:45]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter Ric Elias, the founder of Red Ventures and previous guest on The Drive, returns to discuss his evolving insights on time, relationships, parenting, and how to make the most of the gift of life. In this episode, he reflects on the changes he’s made since his near-death experience during the crash landing of Flight 1549 on the Hudson River in 2009. Ric reveals many keys to living a rich life, such as aiming for continuous growth, approaching life with true intentionality, and valuing our time in accordance with that. He talks about relationships as the core of a rich life and provides insights on parenting and how we should think about our relationship with our kids as they grow older. Finally, Ric discusses the importance of staying true to yourself, the value in struggle, and finding meaning in helping others. We discuss: Reflecting on the tumultuous last few years and how his experience on Flight 1549 helped him [2:30]; Parenting: a game of tug of war that you must ultimately lose [5:00]; Importance of friendship and Ric’s motivation for his recent “Friends summit” [8:00]; The impact of looking forward and focusing on growth on finishing life well [13:00]; How our relationships with our children evolve as they grow, and a new perspective on purpose [21:15]; Living with complete intention for a rich life, valuing your time, and other life lessons inspired by Ric’s near-death experience on Flight 1549 [31:15]; How society’s relationship with work has changed, the pros and cons of remote and hybrid working environments, and an update on his company “Red Ventures” [37:45]; Ric’s dedication to philanthropy [44:45]; The Golden Door Scholars program aiming to help undocumented students with education and a future career [50:30]; Ric’s journey in health and longevity [59:15]; Letting go of guilt and loving yourself [1:02:30]; The relationship between happiness and wealth [1:06:45]; Playing the “infinite game,” staying true to oneself, and ignoring the negative [1:09:15]; Speculating on the meaning of success, the drivers of greatness, and the value of struggle [1:16:00]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter Dan Rader is a Professor at the Perelman School of Medicine at the University of Pennsylvania, where he conducts translational research on lipoprotein metabolism and atherosclerosis with a particular focus on the function of high-density lipoproteins (HDLs). In this episode, Dan goes in-depth on HDL biology, including the genesis of HDL, its metabolism, function, and how this relates to atherosclerotic cardiovascular disease (ASCVD). He explains why having high HDL-C levels does not directly translate to a low risk of cardiovascular disease and reveals research pointing to a better way to measure the functionality of HDL and predict disease risk. He also goes into detail on the role of HDL in reverse cholesterol transport and the benefits this has for reducing ASCVD. Additionally, Dan discusses the latest thinking around the association between HDL cholesterol and neurodegenerative diseases and ends the conversation with a discussion of how the latest research on HDL provides a promising outlook for ongoing trials and future therapeutic interventions. We discuss: The lipidology of apoB and apoA [4:00]; A primer on the high-density lipoprotein (HDL): genesis, structure, and more [9:30]; How the lipoprotein system differs in humans compared to other mammals [20:00]; Clarifying the terminology around HDL and apoA [25:30]; HDL metabolism [31:45]; CETP inhibitors for raising HDL-C: does it reduce CVD risk? [34:45]; Why it’s so important to have hard outcome trials in the field of cardiovascular medicine [42:30]; SR-B1: an HDL receptor important for cholesterol efflux [48:00]; The association between HDL levels and atherosclerosis: are they causally linked? [53:15]; How insulin resistance is impacting HDL, and how HDL-C provides insights into triglyceride metabolism [58:00]; Disappointing results from the studies of niacin—a drug that raises HDL-C and lowers apoB [1:08:15]; HDL lipidation, dilapidation, and reverse cholesterol transport [1:12:00]; Measuring the cholesterol efflux capacity of HDL: a better predictor of ASCVD risk than HDL-C? [1:22:00]; A promising new intervention that may promote cholesterol efflux and reverse cholesterol transport [1:32:45]; The association between HDL cholesterol and neurodegenerative diseases [1:34:00]; Challenges ahead, a promising outlook, and the next frontier in lipidology [1:44:45]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter 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. Connect With Peter on Twitter, Instagram, Facebook and YouTube

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter 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. Connect With Peter on Twitter, Instagram, Facebook and YouTube

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter 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. Connect With Peter on Twitter, Instagram, Facebook and YouTube

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter 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. Connect With Peter on Twitter, Instagram, Facebook and YouTube

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter 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. Connect With Peter on Twitter, Instagram, Facebook and YouTube

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter 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. Connect With Peter on Twitter, Instagram, Facebook and YouTube

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter 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. Connect With Peter on Twitter, Instagram, Facebook and YouTube

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter 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. Connect With Peter on Twitter, Instagram, Facebook and YouTube

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter 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. Connect With Peter on Twitter, Instagram, Facebook and YouTube

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter 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. Connect With Peter on Twitter, Instagram, Facebook and YouTube

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter In this “Ask Me Anything” (AMA) episode, Peter answers a wide variety of questions, starting with a discussion on the evolution of medicine and the hopeful transition to “Medicine 3.0.” Peter recounts his unique career path and explains how he assesses risk and utilizes frameworks for decision-making. He also describes how he prioritizes his health while navigating the stresses of life, and he reviews the most exciting developments in the aging and longevity space. He finishes with some rapid-fire questions on cold plunging, strategies for lowering apoB levels, designing an exercise program for beginners, and 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 #41 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here. We discuss: The evolution of medicine and the transition to “Medicine 3.0” [3:00]; Peter’s unorthodox career arc and what led him to this point [11:45]; What does Peter consider to be his superpowers? [22:15]; How Peter thinks about risk and explains it to his patients when making medical decisions [26:45]; The advantage of using frameworks for decision-making [37:00]; What advice would Peter give his 30-year old self? [42:15]; Why longevity is such a hard problem to solve [42:30]; The most impactful developments in the field of longevity and aging in the last 5 to 10 years [46:15]; What is Peter most excited to see develop in the health and longevity space in the next few years? [51:30]; Prioritizing healthy habits while navigating the stresses of life and time constraints [53:45]; How Peter navigates periods of high stress [58:00]; What fitness watch did Peter recently purchase? [1:03:45]; Potential benefits of cold plunging [1:05:15]; Advice for someone beginning an exercise program [1:07:30]; Strategies and tactics to lower apoB levels [1:09:00]; Interesting studies and books Peter has recently read [1:11:30]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter Erin Michos is an internationally-known leader in preventive cardiology and women’s cardiovascular health. In this episode, Erin discusses current trends in cardiovascular disease (CVD) through the lens of female biology and the observation that major adverse cardiac events in both sexes are on the rise. She walks through risk factors including LDL-cholesterol, apoB, and Lp(a) and makes the case for the importance of early preventative measures. She explains various interventions for reducing risk including a discussion of statins, GLP-1 agonists, PCSK9-inhibitors, and drugs that lower Lp(a). She goes in-depth on female-specific factors that contribute to CVD risk such as pregnancy, grand multiparity (having five or more children), oral contraceptives, menopause, and polycystic ovary syndrome (PCOS). Additionally, she explains her approach with patients as it relates to the use of hormone replacement therapy and provides advice for people wanting to lower risk both through lifestyle changes and medications. We discuss: Erin’s background in preventive cardiology and women’s health [2:30]; Recent trends in cardiovascular disease in women, mortality data, and how it compares to cancer [5:15]; Why early preventative measures are critical for cardiovascular disease risk [13:15]; ApoB as a causal agent of CVD, and why high apoB levels are not being aggressively treated in most cases [19:45]; The rising trend of metabolic syndrome and other factors contributing to the regression in progress of reducing cardiac events [27:00]; GLP-1 agonists—Promising drugs for treating diabetes and obesity [33:30]; Female-specific risk factors for ASCVD (pre- and post-menopause) [37:15]; Polycystic ovary syndrome (PCOS): prevalence, etiology, and impact on metabolic health, lipids and fertility [47:00]; The effect of grand multiparity (having 5+ children) on cardiovascular disease risk for women [52:30]; The impact of oral contraceptives on cardiovascular disease risk [55:00]; The effect of pregnancy on lipids and other metabolic parameters [58:45]; The undertreatment of women with familial hypercholesterolemia (FH) and how it increases lifetime risk of ASCVD [1:02:00]; How concerns around statins have contributed to undertreatment, and whether women should stop statins during pregnancy [1:09:45]; How Erin approaches the prescription of statins to patients [1:16:00]; PCSK9 inhibitors and other non-statin drugs [1:21:15]; Advice for the low- and high-risk individual [1:28:30]; The impact of nutrition, stress, and lifestyle on lipids and CVD risk [1:31:00]; Lp(a) as a risk enhancer for cardiovascular disease [1:41:15]; The effect of menopause on cardiovascular disease risk [1:50:30]; How Erin approaches decisions regarding hormone replacement therapy (HRT) for her patients [1:55:30]; The urgent need for more data on women’s health [2:03:30]; Erin’s goal of running a marathon in every state [2:09:45]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube