The Peter Attia Drive

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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