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In this episode, Robert Sapolsky, Ph.D., discusses the widespread impact of stress on our physical and emotional health as well as the mechanisms by which it can precipitate chronic illness, dementia, depression, and more. He also provides insight into the factors that contribute to the stress response (and our ability to handle it) such as social rank, personality, environment, and genetics. Lastly, we discuss how our behavior is altered in the face of stress and how that not only has a pervasive effect on a personal level, but also on society as a whole in how we interact with each other.

We discuss:

• Background, interest in stress, and Robert’s time in Kenya studying baboons [2:45];
• Physiology of a stress response, and why it’s ingrained in our DNA [9:45];
• Individual variation in the response to stress, and how everyone has a different optimal level [19:45];
• How social rank and personality differences affect our stress response [26:30];
• What’s happening in the brain when faced with stressful situations? [35:00];
• What makes the human brain different than all other species? [44:15];
• Imprinting stress to your kids epigenetically [48:00];
• The role of stress on memory and the consequences of hypercortisolemia [53:00];
• The impact of subjective socioeconomic status and social media on stress levels and health [57:45];
• Tips for managing stress in the modern world [1:13:15];
• What Robert learned about himself studying the social behavior of baboons [1:25:30];
• The multilayered factors behind every human behavior, the context of “good and bad”, and exploring the human capacity of the wild extremes of violence and altruism from moment to moment [1:30:15];
• PMS: How two women with identical hormone levels can have completely different emotional experiences [1:34:45];
• How much of a role do genes play in depression and other emotional states? [1:38:00];
• Why is cortisol elevated under sleep deprivation? [1:46:00];
• The impact of stress on cancer [1:50:30];
• The impact of stress on atherosclerosis, dementia, addiction, and depression [1:57:00];
• Impulsiveness, impaired judgment, and lack of empathy in times of stress [2:01:45];
• What advice would Robert give his 25-year-old self? [2:08:45]; and
• More.

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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.

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Andy Galpin is a Professor of Kinesiology at California State University at Fullerton, where he studies muscle adaptation and applies his research to work with professional athletes. In this episode, Andy 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.

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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.

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Order OUTLIVE

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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.

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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.

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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.

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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.

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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.

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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.

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