The Peter Attia Drive

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 goes into depth on the topic of brain health, starting with how Alzheimer's disease is diagnosed, the significance of blood-based biomarkers in diagnosis, and what the various APOE gene variants mean in terms of a person's risk of developing Alzheimer's disease. Next, Peter discusses the various strategies for preventing Alzheimer's disease and neurodegeneration. He touches briefly on exercise as a potent tool, but focuses more on lesser-known factors that could impact brain health, such as nutrition supplementation, lipid management, brain games, sauna, oral health, hearing loss, 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 our website at the AMA #46 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here. We discuss: Diagnosing Alzheimer's disease [2:45]; Biomarkers for Alzheimer's disease, the C2N test, and other tools for diagnosis [7:30]; Genetic component of Alzheimer's disease: genes that confer risk [12:45]; Understanding your APOE status and why it's important to know [17:15]; The prevalence of Alzheimer's disease and other forms of dementia, and who is at higher risk [21:15]; Can the risk of Alzheimer's disease be decreased with behavioral changes? [24:15]; Overview of modifiable behaviors that potentially play a role in risk reduction of neurodegeneration [30:15]; Things that clearly impact brain health: smoking, alcohol, sleep, head injuries, blood pressure, and more [34:15]; How nutrition impacts brain health: common diets, metabolic health, energy balance, and more [46:15]; Comparing common diets: data showing the association between the incidence of Alzheimer's disease and specific diets [59:45]; Supplements: EPA and DHA, vitamin D, and B vitamins [1:13:00]; Supplements: theracurmin, cocoa flavonols, and magnesium L-threonate [1:25:15]; Impact of exercise on brain health, minimum effective dose, and the most important types of exercise [1:33:00]; Challenging the mind with brain games—does it impact neurodegeneration? [1:43:00]; The data on sauna and brain health [1:49:45]; Oral health and its association with brain health [1:52:45]; How reducing lipids can improve brain health and prevent neurodegeneration [1:55:30]; The potential impact of hearing loss on brain health and neurodegeneration [2:04:30]; 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 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 returns to the podcast and continues the conversation about training for longevity. He examines the training practices of powerlifters, Olympic weightlifters, Strongmen/women, CrossFit athletes, and sprinters in order to extract insights that can be applied to the individual wanting to optimize for longevity. Andy goes into detail about exercise load and repetition, training volume, the importance of learning proper movement patterns, the advantage of working to technical failure instead of the number of reps, and much more. Andy ties the discussion together by providing a hypothetical training plan for an individual wanting to optimize for longevity and offers advice for avoiding injury. We discuss: Review of the function and organization of skeletal muscle [3:15]; Review of muscle fiber types [9:30]; Hypertrophy: changes in muscle fibers and the underlying mechanisms that make a muscle grow [19:30]; Defining sarcoplasmic hypertrophy and how it relates to the number of reps in a set [30:15]; Training for maximum strength: what we can learn from powerlifters and a hypothetical training plan [32:45]; Ideal reps, volume, and load for the powerlifter [44:45]; What should powerlifters do on their off days? [56:45]; Are there consequences of powerlifting on long-term health? [1:02:00]; Defining Olympic weightlifting: a test of power [1:04:30]; Training principles of Olympic weightlifting [1:07:45]; Tracking power output when training [1:17:15]; Frequency of training for Olympic weightlifting [1:22:15]; How post-activation potentiation (and the opposite) can improve power training and speed training [1:24:30]; The Strongman competition: more breadth of movement, strength, and stamina [1:32:00]; Training principles of Strongmen and advice for someone new to the Strongman competition [1:36:45]; CrossFit: a combination of weightlifting movements, endurance, and circuit training [1:50:15]; Learning from elite athletes, heart rate recovery, V02 max, and other metrics [1:58:45]; Optimizing towards being a well-rounded athlete as opposed to a specialist [2:09:45]; What we can learn from the sprinters about speed, acceleration, peak velocity, and technique [2:17:45]; A training plan for the "centenarian athlete" [2:24:30]; Debunking some training and exercise myths [2:33:00]; The "do nots" of training and tips for avoiding injury [2:34:15]; 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 Andrew Huberman is a Professor of Neurobiology at Stanford University and host of the Huberman Lab podcast. In this episode, Andrew begins with a fascinating discussion about the brain, including the role of the prefrontal cortex in adjusting your ruleset to match your setting, the neural circuitry underlying the ability of stress to limit creativity and problem-solving, the effect of belief on physiology and performance, and more. He speaks about vision being our "superpower" and compares this to animals that rely more on other senses. Next, he opens up about his personal journey, the struggles and losses he has overcome, the value of therapy, and the many great people who helped him along the way. He speaks to his love of biology and discovery and the importance of staying true to your passion rather than being driven purely by ambition. Lastly, the conversation includes a look to the future of Andrew's scientific work and podcast as well as his unique approach to communicating science and tackling the issue of scientific illiteracy. We discuss: Exercise under blood flow restriction, lactate utilization, and transient changes in the brain function in response to adrenaline and stress [3:30]; The role of the prefrontal cortex in governing rulesets [9:15]; New discoveries about the circuitry between the prefrontal cortex, insula, and amygdala, and the insights gleaned about brain function in different emotional states [15:30]; Comparing human vision and other senses to animals [26:00]; A deep dive into vision: evolutionary adaptations, facial recognition, color, and more [39:45]; Sense of smell, pheromones, and why evolution developed better vision over smell [46:30]; The relationship between visual input and time perception [55:30]; Mindset effects: the effect of belief on physiology and performance [1:00:45]; Accessing higher levels of creativity with broadening rulesets and the limiting nature of stress and fear on creativity [1:05:30]; Stress and fear increase autonomic arousal, limit access to rulesets, and inhibit performance [1:12:15]; Andrew's upbringing, early childhood, and tough adolescent years [1:15:00]; Andrew's time in a residential treatment program and how he benefited from therapy [1:20:15]; The beginning of positive changes in Andrew's young life [1:28:30]; Andrew's decision to turn his life around [1:37:00]; A new passion for science and exercise helps Andrew [1:42:00]; The difference between a postdoc and a PhD [1:54:15]; Staying in touch with the love of biology and not getting pulled into ambition [1:59:15]; Andrew starts his own lab, and continues work to overcome his demons [2:07:00]; The loss of three mentors leads to deep soul searching [2:12:00]; What motivated Andrew to begin his podcast [2:18:00]; Looking to the future of Andrew's scientific work, podcast, and more [2:22:45]; Andrew's unique approach to communicating science and the issue of scientific illiteracy [2:30:00]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube

Order OUTLIVE View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter's Weekly Newsletter After more than six years of research, planning, and writing, Peter's book, Outlive: The Science and Art of Longevity, is officially available as of March 28th. In this episode, Peter sits down with co-author Bill Gifford to provide a behind-the-scenes look into the writing process, including the motivation for making it happen, how the book evolved over the course of the writing process, and why certain topics were chosen (and omitted). Additionally, they discuss how the book is structured and touch on a few of the book's main themes to give potential readers an idea of what they can expect. We discuss: The meaning of the book's title and subtitle [3:00]; Finding the right art for the book cover [9:00]; Who is Bill Gifford, and how did he get involved in the book? [16:15]; How Peter's writing evolved over the six years it took to write this book [25:00]; The structure of the book and what people can expect to learn [29:00]; How the writing of the book and the podcast interviews have shaped Peter's thinking and approach to translating science [32:45]; Making the book stand the test of time despite the constant evolution of science and medicine [36:00]; Objective, strategy, and tactics [39:30]; Exciting possible progressions in science and medicine over the next decade [42:15]; What is holding back "medicine 3.0" from being the norm? [46:00]; How the book compares to the podcast in terms of technicality and readability for the layman [49:00]; Motivation to write the book and insights into challenges around the writing process [57:15]; Peter's decision to be the reader for the audiobook [1:10:30]; The many painstaking last-minute changes and edits that brought the book together and made it better [1:19:00]; Peter and Bill's favorite parts of the book [1:27:30]; The incredible team of people supporting the book [1:31:30]; 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 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 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

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 special episode of The Drive, we have pulled together a variety of clips from previous podcasts about cardiovascular disease to help listeners understand this topic more deeply, as well as to identify previous episodes which may be of interest. In this episode, Peter highlights the importance of understanding cardiovascular disease and why early intervention is critical. He also provides a primer on lipoproteins and explains the fallacy of the terms "good cholesterol" and "bad cholesterol." Allan Sniderman discusses the metrics measured in routine blood work – along with the limitations of those standard panels – before explaining why apoB is a superior metric for determining risk. Additionally, Tom Dayspring explains the causal role of apoB in atherosclerotic cardiovascular disease (ASCVD) and the therapeutic goals for apoB concentration, and Peter explains how early and aggressive lowering of apoB could change the landscape of cardiovascular disease prevention. We discuss: The importance of understanding atherosclerosis early in life [2:25] Defining ASCVD, its causes, and the role of cholesterol [8:00]; Why early prevention of atherosclerosis is critical [13:45]; Preventing atherosclerosis—two fatal flaws with the "10-Year Risk" approach [16:00]; Intro to lipids and lipoproteins: why there is no "bad" or "good" cholesterol [23:00]; Limitations of standard blood panels [35:45]; How Mendelian randomization is bolstering the case for apoB as the superior metric for risk prediction [39:30]; Therapeutic goals for apoB concentration [58:15]; How early and aggressive lowering of apoB could change the course of ASCVD [1:10:45]; 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 Holly Baxter is an accredited practicing dietician (APD), competitive bodybuilder, fitness and nutrition educator, and coach. In this episode, Holly discusses her experience as an athlete and competitive bodybuilder. She also opens up about her struggles with mental health, her long battle with an eating disorder, and the important steps she's taken in her road to recovery. From there, she explains how she would design a nutrition and training program for a hypothetical female client wanting to improve her physique through the addition of lean muscle and loss of body fat. She explains reasonable expectations for gaining muscle and the value of a "reverse diet" for maintaining weight loss, and she shares her favorite exercises. She also talks through some female-specific training considerations such as programming, reps, volume, hormone replacement therapy, and more. We discuss: Holly's background and passion for sports and nutrition [2:00]; Holly's struggle with depression and an eating disorder [4:30]; Reflecting on her eating disorder, body image, and a wake up call [18:15]; Road to recovery: therapy, meditation, self-compassion, and a breakthrough [27:45]; The effect of competitive bodybuilding on women [39:00]; Holly's competition prep and how she guides her clients wanting to improve their physique [46:45]; Training principles for muscle hypertrophy [57:00]; Training advice for an inexperienced person wanting to build muscle [1:01:30]; Training program for a hypothetical woman wanting to add lean muscle and lose body fat [1:04:15]; Lower body lifts: Holly's approach to leg workouts with clients [1:14:00]; Upper body exercises: Holly's approach with her clients [1:24:45]; Importance of nutrition and protein during the muscle building phase [1:34:00]; Changes to nutrition and training during a fat loss phase [1:40:30]; A "reverse diet" after a cutting phase to help prevent weight gain [1:49:45]; Female-specific training considerations: programming, reps, volume, sex hormones, and more [1:53:15]; Holly's future in bodybuilding and helping struggling women [2:05:45]; Looking forward: Holly's focus on longevity, bone mineral density, and wellness [2:08:15]; 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 discusses the importance of understanding body composition and explains how to interpret the most important metrics revealed by a DEXA scan, such as lean muscle tissue mass, visceral adiposity tissue mass, bone mineral density, and more. He discusses common concerning trends in these metrics as well as strategies to address them. He goes through DEXA scan results of both male and female patient case studies and explains the prescribed intervention for each patient. Additionally, Peter answers numerous questions about dietary protein including how much we need, when we need it, and how intake should be divided throughout the day to optimize muscle protein synthesis. Finally, Peter provides his updated point of view on time-restricted feeding and fasting and how his personal approach and recommendations for patients has evolved. 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 #40 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here. We discuss: Interpreting DEXA scans: important metrics, radiation levels, and more [2:15]; DEXA metrics: Bone mineral density (BMD) [12:00]; DEXA metrics: Visceral adipose tissue (VAT) [14:30]; DEXA metrics on lean tissue: appendicular lean mass index (ALMI) and fat-free mass index (FFMI) [20:45]; Concerning trends in BMD, VAT, & muscle mass revealed through DEXA scans [24:15]; Muscle and lean tissue loss with age and how to overcome anabolic resistance [29:15]; Female patient case studies: DEXA scan results and prescribed interventions [35:00]; Male patient case studies: DEXA scan results and prescribed interventions [42:45]; Protein consumption: recommended daily intake, Peter's personal approach, timing around workouts, and more [48:15]; What to look for with protein supplements [53:15]; Protein intake: optimal timing and how it should be divided throughout the day [55:30]; Time-restricted feeding (TRF): Peter's updated perspective [57:45]; Three strategies for reducing energy intake in over-nourished patients [1:03:15]; Prolonged fasting: potential benefits and tradeoffs [1:07:15]; A protein-supplemented version of time-restricted feeding (TRF) [1:09:30]; Theories about time-restricted feeding (TRF) and its positive influence on sleep and circadian rhythm [1:12:00]; 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 Arthur Brooks is a social scientist, professor at Harvard University, a columnist for The Atlantic, and the bestselling author of From Strength to Strength. In this episode, Arthur explains how intelligence changes as we get older, and how to take advantage of this to maximize our happiness and success. He distills truths about the meaning of happiness and its three main components: enjoyment, satisfaction, and purpose. He goes into detail about many of the keys to a happy life, including the importance of cultivating virtuous relationships. On the flip side, Arthur warns of the dangers of social comparison, "success addition," and the four worldly idols—money, fame, power, and pleasure—that drive many of us. Additionally, Arthur provides examples of exercises that can guide one in the right direction, overcome fear, and cultivate habits that can lead to a happier life. We discuss: Insights from Arthur's career as a professional French horn player [2:15]; A radical shift away from music to a Ph.D. in quantitative policy [12:00]; Personal experience with shifting intelligence: fluid vs. crystallized intelligence [16:45]; An epiphany from a chance encounter on an airplane that shaped Arthur's thinking [22:00]; The three main "macronutrients" of happiness [25:00]; Exploring the "purpose" component of happiness [29:00]; The importance of having a partner and true friendships [32:00]; The makeup of a true friendship, and why men tend to struggle with making real friends [36:45]; The "satisfaction" component of happiness and the importance of "wants management" [42:15]; The tyranny of social comparison [47:45]; Insights into happiness through Chinese art, and the concept of a "reverse bucket list" [51:45]; An exercise demonstrating the importance of relationships with others and the need to work on them [55:30]; The four main idols that drive us: money, fame, power, and pleasure [1:01:15]; Success addiction, workaholism, and their detriment to happiness [1:04:00]; A radical approach to overcome fear—the antithesis to love and happiness [1:14:00]; Ancient Hindu advice for the perfect life [1:26:30]; The end result of getting caught in the 4 idols [1:31:45]; The complexity of happiness [1:33:30]; 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 Michael Easter is the author of the bestseller, The Comfort Crisis. He's also a journalist, Professor of Journalism at UNLV, and a leading voice on how humans can integrate modern science and evolutionary wisdom for improved health, meaning, and performance in life and at work. In this episode, Michael first talks about his upbringing, including his parents' struggle with alcoholism, his father leaving when he was young, and how these things impacted Michael's own struggle with alcoholism. He explains what led to his realization that we are in a "crisis of comfort" and how the removal of many of life's discomforts through advancements in modern society may actually be a leading contributor to many of our most urgent physical and mental health issues. He explains the benefits of challenging oneself and the immense positive carryover which can come from doing things we find difficult. He describes the consequences of technology like smartphones, which have effectively eliminated boredom—a discomfort that comes with many benefits. He tells the story of a profound experience at an elk hunt that changed Michael's thoughts around life and death, how happiness can thrive in places without all of the modern comforts of the West, and why we're hardwired for stress and what to do about it. They conclude with a conversation around rucking, an activity with many physical and mental benefits. We discuss: The value in doing something difficult [2:30]; Michael's upbringing with a single parent and alcoholism [5:45]; Michael's battle with alcoholism and his experience with quitting drinking [10:00]; Origin of the idea that we are in a crisis of comfort [20:30]; The death of boredom in modern society [28:45]; The benefits of boredom [36:00]; The value of disconnecting and being in nature [39:15]; Changing the dynamic of how we think about food and the story of Peter's daughter's first hunt [43:45]; How a profound experience at an elk hunt changed Michael's thoughts about life and death [49:15]; How happiness can thrive in places without all of the modern comforts of the West [57:15]; Why we're hardwired for stress, and the responsibility that comes with our level of comfort [1:05:30]; How perspective on the timescale of our lives in relation to history can impart positive changes [1:14:00]; The benefit of challenging oneself and the positive carryover it can have [1:19:45]; The many benefits of rucking [1:28:45]; Tips for rucking: ideal load, type of pack, and other considerations [1:38:00]; Parting thoughts on the downside of comfort and benefits of difficult things [1:43:00]; 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 Don Layman is a Professor of Food Science and Human Nutrition at the University of Illinois Urbana-Champaign. He has spent the past 40 years investigating the role of dietary protein in muscle protein synthesis. In this episode, Don describes how his decades of research have shaped his thinking around protein, muscle, anabolic factors, metabolism, and more. He explains the recommended dietary allowance (RDA) for protein: what it is, how it came about, and how it should serve only as a guide for the minimum protein necessary for survival rather than as an optimal level of protein intake. He provides an overview of the essential amino acids, explains the nuances of animal versus plant protein, and provides insights for determining protein quality, absorption rates, and how to best track your intake. He discusses the ideal timing of protein intake in relation to resistance exercise, how protein should be distributed among meals, and how limitations in protein utilization per sitting can impact those practicing time-restricted eating. Additionally, Don shares results from his clinical trials, including how a high-protein diet fared in terms of fat loss, and explains the differences in protein utilization between adolescents and adults and how the problem of reduced efficiency of protein utilization in older adults can be overcome. We discuss: Don's background: from growing up on a farm to studying nutritional biochemistry [2:30]; Don's philosophy on nutrition, muscle, and metabolism [6:30]; The controversial relationship between saturated fat and atherosclerosis [18:15]; The basics of protein and amino acids [25:45]; Origin and limitations of the current recommended dietary allowance (RDA) for protein intake [32:15]; Protein sources: determining quality, absorption rates, and how to track intake [41:15]; Leucine, lysine, and methionine: three important essential amino acids [48:00]; The vital role of ruminant animals in the production of quality protein [53:15]; The differing needs and impacts of dietary protein for a 16-year old compared to a 65-year old [59:30]; Consequences of protein deficiency in childhood [1:06:30]; Muscle protein synthesis: ideal timing, small meals vs. big meals, and more [1:12:45]; Protein needs of children [1:19:45]; How important is timing protein intake around training? [1:24:15]; The role of leucine in fatty acid oxidation by muscle [1:28:15]; High protein diets for fat loss: Results from Don's clinical trials [1:31:30]; Influence of industry funding on nutrition studies [1:43:45]; Don's thoughts on plant-based and synthetic "meats" [1:48:45]; Problems with epidemiological studies of dietary protein [1:56:30]; 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 describes what it means to exercise with the goal of longevity in mind, including his personal goals, exercise framework, and how he is optimizing for what he refers to as the "Centenarian Decathlon." He explains the various types of cardiovascular training and how to partition your time between intensity levels (i.e., zone 2 training vs. zone 5 training) to optimize cardiorespiratory benefit. Additionally, Peter dives deep into questions around VO2 max, such as why it's critical for longevity, how to improve it, and the value in starting VO2 max optimization early in life. 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 #39 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here. We discuss: Exercise topics to be discussed [1:45]; Peter's exercise goals, and the Centenarian Decathlon [4:00]; Peter's exercise framework, and how he tracks his MET hours [8:30]; How to partition your time between low and high intensity exercise to optimize results [13:15]; Zone 2 exercise: ideal training methods and how to determine your zone 2 level [23:15]; Rucking as a versatile mode of exercise [31:45]; Zone 5 exercise: modalities of training, time per week, and other considerations [34:30]; The importance of knowing your VO2 max, and methods for estimating it [38:15]; Training methods for improving VO2 max, and realistic targets for improvement [46:00]; Relationship of VO2max with age and the required fitness levels for daily life activities and exercise [52:30]; The training necessary to maintain an elite VO2 max throughout life [58:45]; The value in starting early: the compounding nature of fitness [1:01:45]; 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 Dr. Matt Kaeberlein is a globally recognized expert on the biology of aging and recurring on The Drive. In this episode, Matt explains his research findings on nutrition as it relates to aging and longevity, including the results from his recent review article in Science. From there, he and Peter dive deep into the literature on calorie restriction (CR), explaining the nuance, benefits for lifespan and healthspan, and potential downsides of CR. He discusses the epigenetic changes that occur with age and potential benefits and downsides of epigenetic reprogramming, often viewed as a panacea for reversing aging. Matt also explains the impact of dietary protein on aging, including the interesting dichotomy around how protein, a critical macronutrient, and rapamycin, a geroprotective molecule, have opposite effects on mTOR. Additionally, he talks about low-protein vs. high-protein diets and their effects on muscle mass and mortality, as well as the impact of IGF-1 signaling and growth hormone on lifespan. We discuss: Challenges with understanding the effects of nutrition and studying interventions for aging [3:30]; How Peter's and Matt's convictions on nutrition and thoughts optimal health have evolved [8:15]; Calorie restriction for improving lifespan in animal models [16:15]; Utility of epigenetic clocks and possibility of epigenetic reprogramming [22:00]; Mutations and changes to the epigenome with aging [31:45]; Epigenetic reprogramming: potential benefits and downsides and whether it can work in every organ/tissue [35:15]; First potential applications of anti-aging therapies and tips for aging well [43:00]; Impact of calorie restriction on the immune system, muscle mass, and strength [47:00]; Insights from famous calorie restriction studies in rhesus macaques [55:00]; An evolutionary perspective of the human diet [1:03:45]; Antiaging diets: Separating fact from fiction—Matt's 2021 review in Science [1:12:30]; Mouse models of time-restricted feeding in the context of calorie restriction [1:19:30]; Nutritional interventions that consistently impact lifespan in mice, and concerns around efficacy in humans [1:27:00]; Differing impact of calorie restriction when started later in life [1:31:00]; Lifespan extension with rapamycin in older mice [1:37:15]; Relationship between protein intake and aging, and mouse studies showing protein restriction can extend lifespan [1:43:30]; Impact of protein intake on mTOR, and why inhibition of mTOR doesn't cause muscle loss [1:50:45]; Low-protein vs. high-protein diets and their effects on muscle mass, mortality, and more [1:55:30]; The impact of IGF-1 signaling and growth hormone on lifespan [2:06:30]; Parting thoughts on the contribution of nutrition to healthspan and lifespan [2:19:45]; 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 special episode of The Drive, we have pulled together a variety of clips from previous podcasts with sleep expert Dr. Matthew Walker to help listeners understand this topic more deeply, as well as to identify which previous episodes featuring Matt may be of interest. In this episode, Matt gives an overview of why we sleep, the stages of sleep, and sleep chronotypes, and he provides tips to those looking to improve their total sleep and sleep efficiency. Additionally, Matt discusses the pros and cons of napping, and gives his current thinking on the effects of blue light and caffeine on sleep. Finally, Matt explains the dangers of sleeping pills and reveals what he believes are the most useful alternatives for someone struggling with sleep, such as those with insomnia. We discuss: Evolutionary reasons to sleep [2:15]; Stages of sleep, sleep cycles, and brainwaves [10:00]; Understanding sleep chronotypes and how knowing yours could help you [25:45]; Defining sleep efficiency and how to improve it [36:15]; Correcting insomnia: a counterintuitive approach [38:45]; Pros and cons of napping, and insights from the sleep habits of hunter-gatherer tribes [41:30]; Sleep hygiene, wind-down routine, and tips for better sleep [50:15]; The optimal room temperature and body temperature for the best sleep [59:30]; Blue light: how Matt shifted his thinking [1:08:30]; Caffeine: how Matt has adjusted his hypothesis [1:14:45]; The dangers of sleeping pills, useful alternatives, and cognitive behavioral therapy for insomnia [1:19:45]; 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 Celia Morgan is a Professor of Psychopharmacology at the University of Exeter who has authored numerous publications on the potential therapeutic uses of ketamine in mental healthcare. In this episode, Celia dives deep into the neurobiology of ketamine, how it affects users, and how it differs from other, more classical psychedelics (LSD, MDMA, PCP, and psilocybin). She explains the potential promise of ketamine as a treatment for recalcitrant depression and addiction, and she details the results from her clinical trials in these areas. She discusses the importance of using ketamine in combination with psychotherapy to maximize its benefits, the potential risks associated with ketamine use, and advice for those interested in the therapeutic use of ketamine. We discuss: Celia's training and interest in ketamine [2:15]; The history of ketamine, medical uses, and use as a party drug [3:30]; Neurobiology and pharmacology of ketamine [8:15]; Ketamine regulation and abuse, and how it compares with psychedelics and other molecules [18:15]; Ketamine as a therapeutic for depression [30:45]; The brain under the influence of ketamine and theoretical mechanisms for its anti-depressive effects [48:00]; Risks and concerns with overusing ketamine, and what an intermittent or maintenance dose might look for a patient [57:15]; Treating addiction with ketamine: Celia's studies of alcohol dependance [1:04:00]; Advice for people considering the therapeutic use of ketamine [1:19:45]; 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 Shireen Rizvi is a Professor of Clinical Psychology and Psychiatry at Rutgers University, where she is also the Director of the Dialectical Behavior Therapy Clinic. This episode focuses specifically on dialectical behavior therapy (DBT), a skills-based technique which was originally developed to treat borderline personality disorder (BPD) and has since been adapted to treat depression and other mental health conditions, as well as to help people who have difficulty with emotional regulation and self-destructive behaviors. Shireen explains the origins of DBT and how its creator, Dr. Marsha Linehan, came to find a need for something beyond cognitive behavioral therapy (CBT) when attempting to treat patients with suicidal behavior. From there, Shireen dives into how DBT works to resolve the apparent contradiction between self-acceptance and change to bring about positive changes in emotional regulation, interpersonal effectiveness, mindfulness, distress tolerance, and more. She also provides examples for how one can apply specific skills taught with DBT such as accessing the "wise mind," applying radical acceptance, using the "DEAR MAN" technique, and utilizing an emotion regulation skill called "opposite action." Finally, she explains how the tenets of DBT offer benefits to anyone, and she provides insights and resources for people wanting to further explore DBT. We discuss: The basics of dialectical behavior therapy (DBT) and how it differs from cognitive behavioral therapy (CBT) [3:00]; Treating depression with CBT: history, effectiveness, and how it laid the groundwork for DBT [8:15]; Marsha Linehan's inspiration for developing DBT [16:00]; Explaining borderline personality disorder (and associated conditions) through the lens of DBT [20:00]; How work with suicidal patients led to the development of DBT—a dialectic between change and acceptance [35:30]; Details of DBT: defining the term "dialectical" and how to access the "wise mind" [44:30]; Practicing mindfulness and radical acceptance in the context of DBT [51:00]; Applying "radical acceptance" to tragic scenarios [1:02:00]; The five domains of skills taught in DBT [1:07:15]; Why Marsha chose borderline personality disorder as her focus when developing DBT [1:13:30]; Is there any benefit in doing DBT for someone without a pathological condition? [1:15:45]; The DEAR MAN skill of DBT [1:20:00]; Adapting DBT skills for adolescents and families [1:31:00]; Identifying vulnerability factors, increasing distress tolerance, and the impact of physical pain [1:33:45]; The DBT chain analysis: assessing problem behaviors and identifying vulnerability factors [1:44:30]; Why the regulation of emotions can be so challenging [1:50:30]; The importance of mindfulness skills in DBT [1:53:30]; Opposite action: an emotion regulation skill [1:57:00]; Advice for those wanting to explore DBT [2:03:15]; Finding a well-trained DBT therapist [2:08:15]; 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 dives deep into the question of whether there is such a thing as "too much exercise." He explores the theoretical "J-curve" relationship between exercise and longevity, whereby mortality risk declines with increasing activity levels only to see an uptick above a certain exercise volume threshold. While Peter maintains that exercise is perhaps the single most important tool we have to live longer and live better, he explains the challenges involved in identifying an optimal dose. He takes a hard look at studies—many of which have contradictory results—to highlight major limitations in methodology and how readers could be misled. Additionally, he discusses the rare, but real, risks associated with extreme levels of physical activity and concludes by weighing the benefits against the risks of exercise. If you're not a subscriber and 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 #38 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here. We discuss: How exercise reduces risk for all-cause mortality [2:40]; Defining the metric called "MET" and how it's useful for evaluating different exercises [8:00]; The challenge in determining the optimal exercise doses and the limitations of methods used to study the effect of exercise [13:45]; Using VO2 max as a proxy for fitness to better predict mortality risk [19:30]; Reviewing data which support the theory of a "J-curve" relationship between exercise and longevity [25:00]; Importance of understanding p-values and statistical significance [33:45]; Deconstructing the studies that show a J-curve: major limitations and how one could be misled [37:00]; Peter's takeaways on the theoretical "J-curve" relationship between exercise and longevity [51:30]; Risk of sudden cardiac death from vigorous physical exertion [54:00]; Atrial fibrillation associated with extreme levels of exercise [1:00:15]; Parting thoughts: benefits of exercise far outweigh the risks [1:04:15]; 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 Mike Joyner is a physician-researcher and one of the world's leading experts on human performance and exercise physiology. In this episode, Mike discusses how to combat age-related declines in health and fitness levels by using various modes of exercise to improve lifespan and healthspan. Mike explains the impact of exercise on the autonomic nervous system, blood pressure, heart rate, heart rate variability, heart rate recovery, and max heart rate. He dives deep into VO2 max, including how it's measured, what is driving it, and how to improve it. Mike provides training insights for the average person, including training volume and exercise intensity as well as simple metrics to track. Furthermore, he gives his take on the theoretical "J-curve" relationship between exercise and longevity, as well as whether possible health dangers may be associated with excessive exercise. We discuss: Mike's training as an anesthesiologist and interest in exercise physiology [2:30]; How exercise increases longevity [7:00]; The impressive data on the benefits of exercise [9:45]; The Centenarian Olympics and other ways to mitigate age-related decline in strength and stability [15:00]; The violent dropoff in strength and activity with age and how exercise preserves fitness in old age [19:00]; Benefits of exercise on mortality and fracture risk, and the interplay of nutrition and exercise [22:00]; How exercise benefits the autonomic nervous system and why this plays an important role in our health [26:30]; VO2 max, heart rate recovery, heart rate variability, and other metrics of fitness positively impacted by exercise [28:30]; Reduction in all-cause mortality with increased fitness levels and VO2 max [32:45]; Does the relationship between exercise and longevity follow a J-curve? [40:00]; Mitigating age-related decline in fitness by elevating your VO2 max at a young age [46:15]; Breaking down the variables that drive VO2 max [54:30]; Learning from elite athletes: Training regimens, aerobic efficiency, and other impressive metrics [1:00:15]; Health benefits of light exercise for the average person [1:09:00]; Simple training metrics to track, and Mike's current exercise regimen [1:11:15]; How to boost your VO2 max, and the importance of form and tempo with interval training [1:18:15]; Training advice for the average person [1:25:15]; Why professional athletes have longer careers than they've had in the past [1:27:30]; Use of performance-enhancing drugs in professional sports [1:29:45]; Can the miracle of exercise be put in a pill? [1:36:00]; Mike's current research and questions he's most interested in answering [1:39:00]; Use of convalescent plasma to treat COVID-19 [1:41:15]; Parting thoughts on the current state of fitness and exercise in society [1:47:15]; 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 Josh Rabinowitz is a Professor of Chemistry and Integrative Genomics at Princeton University, where his research focuses on developing a quantitative, comprehensive understanding of cellular metabolism through the study of metabolites and their fluxes. In this episode, Josh focuses the discussion on three main topics: metabolomics, NAD (and its precursors), and cancer metabolism. The metabolomics discussion starts with a broad definition of metabolism, metabolites, and fluxomics before diving deep into glucose metabolism, lactate as a fuel, movement of lactate, and the regulation of these substrates. He then gives a detailed explanation of the electron transport chain and Krebs cycle and their implications with respect to both drugs and nutrition while also explaining how NAD is central to the process of energy generation. He then discusses the age-related decline in NAD and what current literature says about efforts to increase NAD through intravenous or oral supplementation with the precursors NMN and NR, including whether doing so provides any advantage to lifespan or healthspan. Finally, Josh ends the conversation talking about cancer metabolism and how one particular intersection between cancer metabolism and immunotherapy might provide a hopeful outlook on the future of cancer treatment. We discuss: Josh's background and unique path to becoming a research scientist at Princeton [3:30]; What sparked Josh's early interest in metabolism [11:15]; Metabolomics 101: defining metabolites and how they are regulated [16:30]; Fluxomics: metabolism as a system in action [26:00]; The Randle Hypothesis: glucose and fatty acids compete as substrates for oxidation [33:30]; The important role of lactate as an alternate fuel [36:30]; Fasting lactate levels as a potential early indicator of metabolic dysfunction [48:00]; The beauty of the Krebs cycle and the role of NAD in energy production [53:15]; How the drug metformin acts on complex I of the electron transport chain [1:05:00]; The difference between NADH and NADPH [1:08:45]; NAD levels with age, and the efficacy of supplementing with intravenous NAD [1:10:45]; The usefulness of restoring NAD levels and efficacy of oral supplementation with NAD precursors NR and NMN [1:22:15]; Exploring the hypothesis that boosting NAD levels is beneficial [1:32:30]; Cancer metabolism and the intersection with immunotherapy [1:39:00]; Making cancer a chronic disease: exploiting the metabolic quirks of cancer, augmenting the immune system, and more [1:46:15]; The challenge of treating pancreatic cancer [1:50:30]; Epithelial cancers that might respond to metabolic approaches to therapy [1:56:30]; Josh's hopeful outlook on the future of cancer treatment [1:59:00]; Nutritional approaches to cancer attenuation [2:00:15]; What makes Princeton University special [2:06:15]; 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 Mike Gershon is a Professor of Pathology and Cell Biology at Columbia University and has been at the forefront of studying neural control of the gut for the past 60 years. In this episode, Mike gives a tour de force on the pathways of gut-brain communication but first sets the stage with an overview of gastrointestinal tract development and anatomy. He then explains how the gut communicates with the brain and vice versa, from early observations in physiology and anatomy up to our present understanding of what makes the GI tract so unique and complex relative to other organs. He talks about how the gut responds to meals of different food qualities and how that affects satiety signaling to the brain. Additionally, he explains how antidepressants and other drugs impact digestion through effects on serotonin signaling, and he discusses the effects of antibiotics, and what's really going on with "leaky gut." Finally, Mike offers his thoughts on the utility—or lack thereof—of gut microbiome diagnostic tests, and wraps up the discussion by considering how diet, probiotics, and prebiotics impact the microbiome and GI tract. We discuss: The basics of the gastrointestinal (GI) system [3:45]; The very early development of the GI system [9:30]; The unique properties of the blood supply and portal system in the GI tract [12:45]; An overview of gut anatomy and innervation [16:30]; Turnover of the epithelial lining and why cancer rarely develops in the small intestine [26:45]; Nutrient and water absorption in the small and large intestine [30:30]; Ways in which the gut and brain communicate [34:30]; The gut's role in the regulation of appetite [43:30]; The impact of gastric bypass surgery on satiety signals [51:15]; How varicella-zoster virus (VZV) can infect neurons in the gut and create issues later in life [54:30]; The relationship between autism and gastrointestinal illness [1:02:45]; The important role of serotonin in the gut, and the impact of SSRIs on serotonin in the gut [1:09:45]; Defining "leaky gut" and its most common causes [1:16:45]; The gut microbiome [1:30:45]; Fecal transplants: use cases, limitations, and how they illustrate the importance of gut microbes [1:40:45]; Gut microbiome diagnostic tests: why they aren't useful outside of special cases such as cancer detection [1:50:30]; Nutritional approaches to a maintain optimal flora in the gut [1:55:00]; Prebiotics and probiotics, and getting your GI system back on track after a course of antibiotics [2:02:30]; 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 dives deep into the topic of bone health and explains why this is an important topic for everyone, from children to the elderly. He begins with an overview of bone mineral density, how it's measured, how it changes over the course of life, and the variability between sexes largely due to changes in estrogen levels. From there he provides insights into ways that one can improve bone health, from exercise to nutrition supplements to drugs. Additionally, Peter discusses what happens when one may be forced to be sedentary (e.g., bedrest) and how you can work to minimize the damage during these periods. If you're not a subscriber and 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 #37 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here. We discuss: Overview of bone health topics to be discussed [1:45]; Bones 101: bone function, structure, and more [5:15]; Bone mineral density (BMD), minerals in bone, role of osteoblasts and osteoclasts, and more [8:30]; The consequences of poor bone health [13:30]; The devastating nature of hip fractures: morbidity and mortality data [17:00]; Where fractures tend to occur in the body [23:00]; Defining osteopenia and osteoporosis [24:30]; Measuring BMD with DEXA and how to interpret scores [27:00]; Variability in BMD between sexes [34:15]; When should people have their first bone mineral density scan? [36:45]; How BMD changes throughout the life and how it differs between men and women [39:00]; How changes in estrogen levels (e.g., menopause) impact bone health [44:00]; Why HRT is not considered a standard of care for postmenopausal bone loss [47:30]; Factors determining who may be at higher risk of poor bone health [50:30]; Common drugs that can negatively impact BMD [54:15]; How children can optimize bone health and lay the foundation for the future [57:45]; Types of physical activity that can positively impact bone health [1:02:30]; How weight loss can negatively impact bone health and how exercise can counteract those effects [1:10:45]; Nutrition and supplements for bone health [1:14:15]; Pharmaceutical drugs prescribed for those with low BMD [1:17:15]; Impact of extreme sedentary periods (e.g., bedrest) and how to minimize their damage to bone [1:22:00]; 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 Max Diehn is a Professor of Radiation Oncology at Stanford and a clinical radiation oncologist specializing in lung cancer. Max's research focuses on developing novel methods for detecting circulating tumor DNA in the blood of cancer patients and on elucidating the molecular pathways and genes associated with cancer. His interests also include uncovering biomarkers that can predict patient survival, responses to therapy, and disease recurrence. In this packed episode, Max discusses the history of blood-based cancer screening and the importance of understanding the predictive value of tests—sensitivity, specificity, negative predictive value, positive predictive value – and how these metrics play into cancer screening. Max then goes in depth on the topic of liquid biopsies, including the history, current landscape, and possible future of liquid biopsies as a cancer detection tool. He discusses how these non-invasive blood tests can detect DNA/RNA from tumor cells released into the blood as well as the different methods one can use to predict if a cancer is present. He gets granular on the topic of cell-free DNA/RNA signature, methylation patterns, and the importance of knowing mutation information, and he ends with a discussion on the exciting future of liquid biopsies and how we can possibly get to the panacea of cancer screening. We discuss: Max's training that planted the seeds for development of liquid biopsies [4:30]; Max's decision to specialize in radiation oncology [11:45]; A culture at Stanford that values research and physician scientists [17:00]; The motivation to develop liquid biopsies [19:15]; History of blood-based cancer screening and understanding the predictive value of tests [25:30]; Current state of lung cancer and the need for better screening [32:45]; Low-dose CT scans: an important tool for managing lung cancer but with limitations [42:00]; Using liquid biopsies to identify circulating tumor cells [47:00]; Liquid biopsy research moves from circulating tumor cells to cell-free DNA [1:03:00]; Zeroing-in on circulating tumor DNA in cell-free DNA [1:10:48]; Cell-free RNA and Max's vision for cancer detection from a blood sample [1:22:00]; Methylation patterns and other informative signatures found in DNA [1:24:30]; Mutation-based methods of liquid biopsies [1:26:30]; Understanding the sensitivity and specificity of a diagnostic test [1:30:30]; Existing clinical liquid biopsy tests and their limitations [1:37:30]; The future of liquid biopsies [1:44:00]; How we get to the panacea of cancer screening [1:52:00]; 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 episode, Ric Elias, founder of Red Ventures, opens up about the fateful day he knew for certain that he was going to die as a passenger on US Airways Flight 1549. Ric dives deep into how that day impacted his life, greatly changed his perspective, and improved his relationship with his family and the broader community. We also talk about his incredible role as CEO of an enormous company, his remarkable work in philanthropy, and all the wisdom he has acquired in his extraordinary life. We discuss: Ric's life leading up to the day of the plane crash [2:15]; The plane crash—What it's like knowing you're about to die, feelings of regret and sadness [8:00]; The improbable plane landing in the Hudson River [15:45]; Emotions after the safe landing (and a story he's never told before) [22:15]; A powerful story about Captain Sully [26:15]; Earning his second chance at life, and playing the "infinite game" [35:15]; Why time is the ultimate currency, and how (and why) to say "no" [43:00]; Raising kids in an achievement culture, Ric's definition of life success, and what Ric wants to instill in his kids [49:45]; What Ric believes is actually worth getting upset about, and the organizations that are taking steps to help people [1:05:45]; The core principles of Red Ventures (Ric's company) [1:16:00]; Ric's tips for developing business acumen and negotiation skills [1:26:15]; What qualities does Ric look for in people he wants to work with? [1:29:15]; What is the next big problem that Ric wants to solve? [1:32:15]; What is the most challenging part of your business today? [1:34:15]; If Ric could go back and talk to himself in the morning before getting on that plane, what would he say? [1:36:00]; 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 Stephan Guyenet is a neuroscientist focused on the neuroscience of obesity and energy homeostasis. He is the author of the book, The Hungry Brain and founder/director of Red Pen Reviews. In this episode, Stephan explains how obesity has changed phenotypically over the course of human history as well as what might explain the dramatic increase in prevalence of obesity in the last few decades. He talks in depth about the role of genetics, the brain, and hormones like leptin play in the regulation of fat mass. He dives deep into two common theories of obesity—the carbohydrate-insulin model and the energy balance model and provides his take on which theory has stronger evidence. Additionally, he provides insights on how we're hard-wired to think about food and the consequences of modern foods designed for maximal pleasure. Finally, he goes through the factors that affect body weight, set points, and provides takeaways for people wanting to take advantage of what we know about the brain's role in regulating our body weight. We discuss: Stephan's neuroscience background and his focus on the nuances of obesity [2:15]; How obesity has changed for humans throughout history [8:00]; The association between obesity and adverse health outcomes, the "obesity paradox," and confounders when relating BMI to longevity [14:00]; The sharp increase in obesity across demographics [23:30]; The hypothalamus and its role in obesity [30:00]; The role of the hormone leptin in obesity [40:00]; The genetic component of obesity [46:30]; Understanding the tendency of humans to store fat through an evolutionary lens [57:00]; The hedonic aspect of food, and how the brain reacts to modern, highly-rewarding foods [1:03:30]; How we are hard-wired to think about food [1:14:30]; A review of the "Carnivore diet" [1:21:45]; The energy balance model, carbohydrate-insulin model, and unifying the theories around adiposity [1:34:15]; Body weight set points: a hypothetical comparison of two individuals [1:41:45]; Takeaways for people who want to lose weight and keep it off [1:48:30]; Evidence that favors the energy balance model of weight gain [1:56:00]; The synergistic effect of fat and carbohydrates and observations that a low-fat diet or a low-carb diet can cause weight loss [2:04:30]; Red Pen Reviews [2:11:00]; 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 discusses the nutritional profiles of various fruits and vegetables as a means of assessing their relative value. He explains the difference between eating them vs. drinking them, how processing fruits and vegetables can change their properties, and how one's current state of health affects nutrition strategy when it comes to fruits and vegetable consumption. Additionally, Peter explains the potential benefits and negative effects of certain phytochemicals found in produce and concludes with a discussion of supplementing with green powders, multivitamins, and more. If you're not a subscriber and 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 #36 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here. We discuss: The limitations of nutritional data and challenges of making broad recommendations [2:00]; How one's current state of health impacts their "optimal" diet [11:30]; Defining "metabolic health" [14:45]; The wide-ranging nutrition profiles of various fruits and vegetables [16:30]; The benefits of fiber [20:45]; Eating whole fruits vs. drinking fruit juice or smoothies [22:30]; Drinking alcohol: metabolic effects, calories in alcohol, and more [28:30]; Can excess fruit consumption lead to insulin resistance? [30:30]; Glycemic impact of different fruits, using CGM data to assist decision making, and how fruit is fundamentally different from what we evolved to eat [31:30]; Dietary approaches for people with a carbohydrate tolerance disorder (TD2, NAFLD, etc.), and when it makes sense to restrict fruit consumption [34:30]; Nutrition profile of select vegetables: sugar content, micronutrients, and more [40:00]; Phytochemicals in produce: potential positive health impacts on inflammation, cardiovascular (CV) risk, and cancer [44:30]; Phytochemicals with potential negative health impacts [50:45]; Nightshades and inflammation [53:15]; How important is it to eat organic foods? [56:00]; How necessary is it to wash fruits and vegetables? [1:00:45]; How does food preparation change the nutritional composition? [1:03:45]; Considerations when eating canned and frozen food, and paying attention to processed food additives [1:04:45]; Supplementing vitamins and nutrients as an alternative to eating whole fruits and vegetables [1:06:15]; Green powder supplements [1:11:15]; Important takeaways [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 Benoît Arsenault is a research scientist focused on understanding how lifestyle and genetic factors contribute to cardiovascular disease risk. In this episode, the discussion casts a spotlight on Lp(a)—the single most important genetically-inherited trait when it comes to atherosclerotic cardiovascular disease (ASCVD) risk. Benoît explains the biology of Lp(a), how it's inherited, the importance of measuring Lp(a) levels, and the diseases most associated with high Lp(a). He dives into data on the possible treatments for lowering Lp(a) such niacin, statins, and PCSK9 inhibitors, as well as the most exciting new potential therapeutic—antisense oligonucleotides. We discuss: How Benoît came to study Lp(a)—a new marker for cardiovascular risk [3:15]; The relationship between Lp(a) and CVD risk [6:45]; What genome-wide association studies (GWAS) revealed about Lp(a) [16:00]; Clinical tests to measure Lp(a) [22:00]; The biology of Lp(a) [25:45]; How statins lower LDL-cholesterol and why this doesn't work for an Lp(a) [29:15]; The structure of LDL-p and Lp(a) and what makes Lp(a) more atherogenic than an equivalent LDL particle [34:00]; The role of Lp(a) in aortic valve disease [42:45]; How greater numbers of Lp(a) particles are associated with increased risk of disease [48:00]; The genetics and inheritance of Lp(a) and how and when to measure Lp(a) levels [52:00]; Niacin and other proposed therapies to lower Lp(a), apoB, and CVD risk [1:00:45]; Why awareness of Lp(a) among physicians remains low despite the importance of managing risk factors for ASCVD [1:14:00]; The variability of disease in patients with high Lp(a) [1:19:00]; Diseases most associated with high Lp(a) [1:26:30]; The biology of PCSK9 protein, familial hypercholesterolemia, and the case for inhibiting PCSK9 [1:35:00]; The variability in PCSK9 inhibitors' ability to lower Lp(a) and why we need more research on individuals with high levels of Lp(a) [1:50:30]; Peter's approach to managing patients with high Lp(a), and Benoît's personal approach to managing his risk [1:54:45]; Antisense oligonucleotides—a potential new therapeutic for Lp(a) [1:57:15]; 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 Marty Makary is a surgeon, public policy researcher, and author of the New York times best-sellers Unaccountable and The Price We Pay. In this episode, Marty dives deep into the topic of patient safety. He describes the risk of medical errors that patients face when they walk into the hospital and how those errors take place, and he highlights what amounts to an epidemic of medical mistakes. He explains how the culture of patient safety has advanced in recent decades, the specific improvements driven by a patient safety movement, and what's holding back further progress. The second half of this episode discusses the high-profile case of RaDonda Vaught, a nurse at Vanderbilt Hospital convicted of negligent homicide after she mistakenly gave a patient the wrong medication in 2017. He discusses the fallout from this case and how it has in some ways unraveled decades of progress in patient safety. Furthermore, Marty provides insights in how to advocate for a loved one in the hospital, details the changes needed to meaningfully reduce the death rate from medical errors, and provides a hopeful vision for future improvements to patient safety. We discuss: Brief history of patient safety, preventable medical mistakes, and catalysts for major changes to patient safety protocols [0:12]; Advancements in patient safety and the dramatic reduction in central line infections [14:55]; A surgical safety checklist—a major milestone in patient safety [23:03]; A tragic case stimulates a culture of speaking up about concerns among surgical teams [25:19]; Studies showing the ubiquitous nature of medical mistakes leading to patient death [29:42]; The medical mistake of over-prescribing of opioids [33:48]; Other types of errors—electronic medical records, nosocomial infections, and more [35:43]; Importance of honesty from physicians and what really drives malpractice claims [40:26]; A high-profile medical mistake case involving nurse RaDonda Vaught [47:31]; Investigations leading to the arrest of RaDonda Vaught [59:48]; Vaught's trial—a charge of "negligent homicide" [1:05:16]; A guilty charge and an outpouring of support for Vaught [1:12:09]; Concerns from the nursing profession over the RaDonda Vaught conviction [1:18:09]; How to advocate for a friend or family member in the hospital [1:20:22]; Changes needed for meaningful reduction in the death rate from medical errors [1:26:42]; Blind spots in our current national funding mechanism and the need for more research into patient safety [1:31:42]; Parting thoughts—where do we go from here? [1:35:48]; 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 Kelsey Chittick is the author of Second Half: Surviving Loss and Finding Magic in the Missing. In this episode, Kelsey describes her long healing process following the sudden death of her husband, former NFL player Nate Hobgood-Chittick. She describes her life with Nate before and after football, including her premonitions that something was off about Nate and the subsequent finding that he suffered from chronic traumatic encephalopathy (CTE). She speaks openly about how she handled his death with her children, the trauma and grief they faced in the aftermath, and how she's found ways to be happy in her new life. She shares deep insights into her healing process, including her experience with psychedelics and how the concept of "radical acceptance" has helped her to find joy once again. We discuss: Kelsey's childhood in Florida as an athlete [2:15]; Meeting Nate and early relationship with him [7:45]; Nate's unbelievable work ethic and desire to play in the NFL [12:30]; Life with a professional football player, playing through pain, and head injuries related to football [17:00]; Nate's final days of football and early retirement struggles [23:30]; The tough transition from the NFL to a "regular life" and how Nate found a way to serve others [28:45]; Nate's struggle with his weight and overall health after retirement [34:45]; Kelsey's anxiety and premonitions of Nate's impending death, and Nate's changing demeanor [37:30]; The traumatic experience of learning of Nate's death during her own spiritual journey to Jamaica [45:30]; Breaking the news to her children of their father's death [51:00]; The darkest days following Nate's passing and how her children were handling grief [55:30]; A new relationship with death, finding happiness, and the duality of feelings [1:02:45]; Nate's autopsy results showing evidence of CTE [1:07:00]; The grieving process [1:15:00]; Dealing with grief with kids and how children grieve differently [1:19:15]; Healing through her first psychedelic experience [1:23:00]; The therapeutic potential of psychedelics, meditation, and more [1:33:45]; The concept of "radical acceptance" and the peace that comes with it [1:42:30]; The up and down experience of writing her book [1:47:45]; 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 is joined by special guest, Dr. Matt Kaeberlein. Together they answer many questions around the field of aging with an emphasis on three specific molecules—NAD, metformin, and rapamycin—and their purported geroprotective qualities. They first discuss aging biomarkers and epigenetic clocks before breaking down the advantages and limitations of the most common experimental models being used today to study aging and pharmacological possibilities for extending lifespan. Next they dive deep into NAD and the much-hyped NAD precursors, nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN). They compare data from NAD precursors to studies on metformin and rapamycin, assessing how they stack up against each other and using the comparison as an opportunity to illustrate how to make sense of new experimental data and make smart decisions about how to approach future research. If you're not a subscriber and 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 #35 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here. We discuss: Logic behind comparing NAD precursors to rapamycin and metformin [3:40]; Aging biomarkers: current state, usefulness, and future promise [7:00]; Epigenetic clocks: definition, use case, and limitations [14:45]; Advantages and limitations of studying aging in non-humans and the strengths and weaknesses of different model systems [26:30]; Aging studies: importance of control lifespans and the problems with reproducibility [34:15]; Intro to NAD, potential role in aging, relationship to sirtuins, and more [48:15]; NAD precursors (NR and NMN): current data [1:10:00]; Human studies with NAD precursors [1:25:45]; Comparing NAD lifespan data to data from metformin and rapamycin [1:28:30]; Defining a "clean drug" and a "dirty drug" [1:38:00]; Reason for the lack of rapamycin studies in humans compared to NAD and metformin [1:41:00]; Ranking the geroprotective molecules in terms of risk and reward [1:48:00]; 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 special episode of The Drive, we have pulled together a variety of clips from previous podcasts about exercise to help listeners understand this topic more deeply, as well as to identify previous episodes which may be of interest. In this episode, Peter discusses his framework for exercise, what he's really optimizing for, and how to train today to be prepared for a good life at age 100. He describes the importance of strength and stability, and why deadlifting is an important tool to consider for longevity. Additionally, he details why training in zone 2 and zone 5 is important, gives a primer on VO2 max, and describes the most effective ways to engage in those types of exercise. Finally, Peter reveals his current exercise routine. We discuss: What is Peter optimizing for with his exercise? [3:00]; Preparing for a good life at age 100: Training for the "Centenarian Olympics" [6:00]; The importance of preserving strength and muscle mass as we age [21:45]; The value of deadlifts for stability and longevity when done properly [27:30]; The importance of zone 2 aerobic training [35:45]; The most effective ways to engage in zone 2 exercise [40:00]; Zone 5 training and VO2 max [44:15]; A primer on VO2 max [52:00]; Stability—the cornerstone upon which all exercise and movement relies [1:03:00]; Peter's current exercise routine [1:07:45]; 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 previous guest on The Drive. In the first half of this episode, Layne dives deep into the topic of energy balance, including the role that macronutrients and calories play in weight loss. He describes how many people struggle with tracking food and calories on their own across a variety of diets and how all of this can impact nutritional habits and behaviors. In the second half of the episode, Layne discusses the importance of protein and weightlifting for improving one's body composition and increasing muscle mass. He explains how he would prescribe different training and nutrition programs for two hypothetical clients—a 50-year-old female who is entering menopause and wants to improve her health, and a 40-to-50-year-old male who wants to maximize muscle mass. Additionally, Layne discusses a number of supplements that could potentially benefit a training program including whey protein, branch chain amino acids, creatine, nitric oxide boosters, and more. We discuss: Defining energy balance and the role of calories [2:30]; Defining a calorie, whether they are all created equal, and how much energy you can extract from the food you eat [8:00]; Factors influencing total daily energy expenditure [12:15]: The challenge of tracking energy expenditure accurately, and the thermic effect of different macronutrients [23:30]; Challenges of sustained weight loss: metabolic adaptation, set points, and more [34:45]; Weight loss strategies: tracking calories, cheat meals, snacks, fasting, exercise, and more [40:45]; Sitting in discomfort, focusing on habits, and other lessons Layne learned as a natural bodybuilder [52:15]; Commonalities in people who maintain long-term weight-loss [1:01:15]; Does a ketogenic diet result in greater energy expenditure? [1:03:15]; The metabolic benefits of exercise, muscle mass, and protein intake [1:15:00]; The impact of lean muscle and strength on lifespan and healthspan [1:20:00]; Hypothetical case study #1: Training program for 50-year-old female [1:27:45]; Muscle protein synthesis in a trained athlete vs. untrained individual following a resistance training program [1:31:30]; Protein and amino acids needed to build and maintain muscle mass [1:37:15]; Nutrition plan for the hypothetical 50-year-old woman starting to build lean muscle [1:42:45]; Dispelling myths that excess protein intake increases cancer risk through elevations in mTOR and IGF [1:55:30]; Hypothetical case study #2: Training program for a 50-year-old, trained male wanting to increase muscle mass [2:04:00]; Maximizing hypertrophy while minimizing fatigue—is it necessary to train to muscular failure? [2:11:30]; Ideal sets and reps for the hypothetical 50-year-old male interested in hypertrophy [2:16:15]; Maximizing hypertrophy by working a muscle at a long muscle length [2:22:15]; Recommended lower body exercise routines and tips about training frequency [2:24:00]; Nutrition plan for the hypothetical 50-year old male wanting to add muscle [2:29:00]; Cycling weight gain and weight loss when building lean muscle mass, and expectations for progress over time [2:33:30]; Supplements to aid in hypertrophy training [2:38:30]; 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 Nir Barzilai, Director of the Institute for Aging Research at the Albert Einstein College of Medicine, is back for his third appearance on The Drive. In this episode, Nir divulges insights into lifespan and healthspan through the lens of his extensive research on centenarians as well as the latest from the TAME trial (Targeting/Taming Aging with Metformin), a multi-center study investigating the concept that the multi-morbidities of aging can be delayed in humans. He discusses common gene variants found in centenarians, important pathways for longevity, and ultimately what we can learn from centenarians about extending lifespan while also trying to improve healthspan. Additionally, Nir goes into depth on metformin as a longevity tool for humans, including studies with positive and negative results. He discusses the impact metformin can have on exercise for both strength training and cardiovascular training, as well as future research facilitated by data from the TAME Trial. He also touches on epigenetic clocks and concludes with his take on the usefulness of NAD precursors as a potential gero-protective agent. We discuss: Insights from genetic studies of centenarians and twins [3:00]; Genes with protective variants that aid longevity [13:00]; The relationship between growth hormone and IGF-1 [22:45]; Use of growth hormone as a longevity tool [34:00]; Longevity genotypes: the role of APOE e2, Lp(a), Klotho, and CETP [41:45]; The correlation between high TSH and longevity [46:30]; Important pathways for longevity [52:00]; Insights from centenarian studies, nature vs. nurture, and more [59:00]; The contraction of morbidity that comes with improved healthspan [1:08:00]; Defining healthspan [1:13:13]; Unique perspectives and positive attitudes of centenarians [1:17:30]; Lessons to take away from centenarians [1:24:00]; Metformin overview: history, studies, and potential for gero-protection [1:28:45]; The TAME trial (Targeting Aging with Metformin) [1:39:00]; The challenge of studying metformin in animals models [1:46:45]; How data from the TAME trial could provide insights into biomarkers of aging and facilitate a future study on proteomics [1:53:30]; The search for biomarkers to identify who can benefit from treatment [2:00:30]; The impact of metformin on exercise, and finding the right indication for the use of metformin [2:10:30]; Are NAD precursors geroprotective? [2:21:30]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube