In this episode, my good friend David Sabatini delves into his extensive work with the mechanistic target of rapamycin—better known as mTOR—and rapamycin. The compound rapamycin is the only known pharmacological agent to extend lifespan all the way from yeast to mammals—across a billion years of evolution. David, a professor of biology and a member of the Whitehead Institute at MIT, shares his remarkable journey and discovery of mTOR in mammalian cells and its central role in nutrient sensing and longevity. Fasting, rapamycin, mTOR, autophagy, gedankenexperiments: having this conversation with David is like being the proverbial kid in the world’s greatest candy store. We discuss:  mTOR and David’s student years [4:30]; Rapamycin and the discovery of mTOR [8:15]; The connection between rapamycin, mTOR, and longevity [30:30]; mTOR as the cell’s general contractor [34:45]; The effect of glucose, insulin, and amino acids on mTORC1 [42:50]; Methionine sensing and restriction [49:45]; An intermittent approach to rapamycin [54:30]; Rapamycin’s effects on cancer, cardiovascular disease, and neurodegeneration [57:00]; Gedankenexperiment: couch potatoes on rapamycin vs perfectly behaved humans [1:03:15]; David’s dream experiment with no resource constraints [1:07:00]; and More.    Learn more at www.PeterAttiaMD.com  Connect with Peter on   Facebook |   Twitter |   Instagram.

#09 - David Sabatini, M.D., Ph.D.: rapamycin and the discovery of mTOR — the nexus of aging and longevity?

Expert insight on health, performance, longevity, critical thinking, and pursuing excellence. Dr. Peter Attia (Stanford/Hopkins/NIH-trained MD) talks with leaders in their fields.

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 View the Show Notes Page for This Episode  Become a Member to Receive Exclusive Content  Sign Up to Receive Peter’s Weekly Newsletter Paul Conti is an author and practicing psychiatrist who specializes in helping people heal from trauma. In this episode, Paul returns to The Drive to delve into the intricate relationship between emotional health, healthspan, and lifespan. He first challenges common assumptions about the inevitable decline of emotional health with age, providing strategies for conducting a comprehensive audit of internal emotional health. He establishes a framework for the foundation of good emotional health: a balance between the generative drive, the assertive drive, and the pleasure drive. Paul also explores the nuanced dynamics of motivation, happiness, and satisfaction as it relates to material possessions, draws connections between physical and emotional well-being, confronts the impact of negative self-talk, and describes how making peace with our mortality can foster a sense of hope, purpose and well-being. Additionally, Paul offers many practical insights into initiating emotional health improvements and navigating the search for a suitable therapist. We discuss:  The importance of prioritizing emotional health as we age [2:45]; The impact of emotional health on healthspan and how to foster a proactive approach to emotional well-being [7:00]; The discrepancy between outward success and inner fulfillment, and the importance of a healthy “generative drive” for genuine well-being [13:00]; A deeper dive into generative drive: impact on human behavior, resilience, purpose, and more [23:15]; Evaluating one’s inner self: introspection, self-awareness, challenging societal norms, and returning to the basics of physical and emotional well-being [29:00]; Self-auditing tools: introspection, curiosity, and exploring underlying reasons for unwanted behaviors [41:45]; Breaking free from destructive cycles by understanding the continuum of self-care and addictive behaviors and remaining curious [50:15]; Critical self talk: the malleability of one’s inner dialogue and the potential for transformative change with perseverance and self-compassion [1:00:15]; Slowing the anger response and gaining insights into the underlying triggers to achieve lasting change and self-understanding [1:13:45]; Foster gratitude and humility by achieving balance between the three drives—assertion, pleasure, and generative [1:20:45]; The conflict between intellectual understanding and emotional feelings, problematic comparison frameworks, and the importance of living in the present with intentionality [1:24:15]; How making peace with our mortality can foster a sense of hope, purpose and well-being [1:34:45]; Advice for finding a compatible therapist [1:43:45]; The key components of therapeutic progress [1:57:00]; The caricatures of four common patient phenotypes, and how to get through to them [2:05:30]; How Paul manages his own well-being and the emotional challenges that come with his line of work [2:15:15]; and More.  Connect With Peter on Twitter, Instagram, Facebook and YouTube

#298 ‒ The impact of emotional health on longevity, self-audit strategies, improving well-being, and more | Paul Conti, M.D.

 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 delves into the crucial yet often overlooked topic of iron and iron deficiency. He explores why iron is indispensable for the body, explains the repercussions of iron deficiency, and sheds light on the prevalence of this issue and who is most susceptible. Peter outlines strategies for increasing iron levels, covering dietary iron, supplementation, and infusion options, while also discussing the suitability of each approach for different individuals. Shifting gears, Peter tackles rapid-fire questions on creatine and sodium, as well as inquiries related to his book. 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 #58 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here. We discuss:  Overview of today’s topics and the importance of understanding iron levels in the body [1:45]; The importance and ubiquity of iron in the body, and the role of the protein called ferritin [4:30]; The processes of iron absorption, utilization, and transportation [9:30]; Options for testing iron levels and how to interpret the results [13:45]; What does it mean to be iron deficient, and how is it different from anemia? [17:15]; Symptoms of iron deficiency and/or anemia [22:15]; How prevalent is iron deficiency, and who is most susceptible? [24:30]; The importance of consuming an adequate amount of iron daily to prevent deficiency [30:30]; The best way to improve iron levels for someone who is deficient [34:45]; Iron supplementation: various formulations and potential side effects [37:45]; Intravenous iron infusion as an alternative to oral supplements -- plus restless legs syndrome and other topics [42:00]; Iron supplementation: who should and should not consider it [44:00]; Peter’s approach to creatine and his pre- and post-workout supplements [50:15]; Navigating sodium intake: effect on blood pressure, who should use precaution, and other considerations [54:45]; Peter’s thoughts about the potential of writing another book [57:15]; and More.  Connect With Peter on Twitter, Instagram, Facebook and YouTube

#297 - AMA #58: Iron: its role in health, testing methods, and strategies for preventing and managing iron deficiency

 View the Show Notes Page for This Episode  Become a Member to Receive Exclusive Content  Sign Up to Receive Peter’s Weekly Newsletter Courtney Conley is an internationally renowned foot and gait specialist. In this episode, Courtney delves into the intricate world of foot anatomy and functionality. She explores the complexities of the foot, discussing its anatomy, common injuries, and the importance of understanding its structure in preventing issues. She covers a range of foot ailments, factors contributing to them, treatment options, and prevention strategies. She delves into the significance of loading, balance, range of motion, and posture, emphasizing the crucial role of strength in preventing both injuries and falls. Additionally, she sheds light on the interconnectedness of the kinetic chain, from the leg muscles down to the foot, and how issues within this chain can cascade downstream, leading to various injuries and pathologies. Additionally, she provides a comprehensive overview of footwear, discussing suitable options for both adults and children to promote foot health and mitigate potential problems. In addition to this interview, Courtney also recorded a series of videos to better explain a number of the concepts discussed such as diagnostic tests that are used to determine mobility and strength and the exercises one should perform to improve the outcomes based on the diagnostics. The interview will be available to everyone while the videos from the gym will only be available to paid subscribers (found at the end of the show notes page). We discuss:  Why Courtney chose to specialize in the foot [3:30]; The vital role of foot strength, function, and health in human movement and well-being [6:15]; Anatomy of the rear foot and midfoot [10:15]; The development of flat feet, the impact of footwear, and the benefits of going barefoot [19:45]; Anatomy of the forefoot, common injuries, and why most injuries occur in the forefoot [23:15]; Foot musculature and its role in maintaining foot stability and preventing deformities like bunions and hammer toes [30:15]; The intrinsic musculature of the foot, plantar fasciitis, footwear, and more [39:00]; Plantar fasciitis: diagnosis, causes, and treatment [51:30]; Posterior leg muscles: strength assessment methods, role in ACL injuries, and more [59:15]; Lateral and medial muscles: ankle stability, arch support, big toe stabilization, and exercises to strengthen and prevent injuries [1:04:15]; Importance of strength of lower leg muscles for gait and preventing shin splints, stress injuries, and more [1:08:15]; Tendinopathies and other common pathologies related to the anterior and lateral compartments of the foot [1:13:00]; The importance of midfoot integrity, ankle dorsiflexion, and a discussion of gait alterations [1:19:45]; Proximal stability and its implications for posture and movement patterns [1:27:00]; The age-related decline in foot sensation and strength [1:32:45]; Common toe injuries, treatment, and how to prevent further progression of the injury [1:36:30]; Preventing falls and managing arthritis with proactive foot care and exercises [1:46:45]; Footwear: advice for picking shoes that promote foot health [1:54:45]; Footwear for runners [2:05:30]; The importance of prioritizing footwear that promotes natural foot movement and strength while considering individual comfort and foot health needs [2:09:30]; and More.  Connect With Peter on Twitter, Instagram, Facebook and YouTube

#296 ‒ Foot health: preventing and treating common injuries, enhancing strength and mobility, picking footwear, and more | Courtney Conley, D.C.

 View the Show Notes Page for This Episode  Become a Member to Receive Exclusive Content  Sign Up to Receive Peter’s Weekly Newsletter Mark Rosekind is an expert on road safety and a policy leader with more than 30 years of experience enacting strategic, practical, and effective data-based solutions that enhance driver and pedestrian safety and health in complex environments. In this episode, Mark delves into the persistent issue of accidental deaths resulting from roadway accidents, a concern for those focused on longevity given its consistent risk throughout life. From exploring statistics on car crashes to identifying the demographics most at risk and the key locations of incidents, he uncovers various risk factors including distractions like smartphone usage, the influence of alcohol and cannabis, the dangers of sleep deprivation, and speeding. Mark also provides practical advice for both drivers and pedestrians to enhance safety, while delving into the potential and challenges of emerging technologies such as autonomous vehicles. Additionally, Mark provides valuable resources for listeners, particularly parents navigating the road safety landscape with teenage drivers. We discuss:  Mark’s background and education, and the profound impact of transportation accidents on human lives [4:15]; From sleep science to safety leadership: Mark’s journey in transportation innovation [14:15]; Stats on transportation accidents and fatalities [18:00]; Historical trends in road fatalities and the key contributors—impairment, distraction, and more [28:00]; The demographics of drivers involved in crashes, and the life-saving potential of better driver education programs [34:30]; The most critical areas where drivers need to be hyper-aware to protect themselves [41:00]; The role of the National Transportation Safety Board (NTSB) in accident investigations, and the importance of data sources like event data recorders (EDRs) in accident reconstruction and investigations [47:00]; The dangers of phone use while driving [53:45]; How drunk driving was addressed through advocacy and legal changes [1:01:30]; The need to address distracted driving and the psychological impact of distracted driving accidents on both victims and perpetrators[1:07:15]; Navigating the roads and lowering your risk of accidents: weather, human error, and defensive driving [1:15:45]; The impact of impaired driving: alcohol, cannabis, prescription drugs, and more [1:26:15]; Mitigating the effects of vehicle speed [1:38:15]; The promise and challenges of autonomous vehicles for road safety [1:44:15]; Automatic emergency braking (AEB): the effectiveness and challenges of implementing AEB as a standard feature in new vehicles [1:53:00]; Sleep deprivation: the impact of poor sleep, drowsiness, and disrupted circadian rhythm on driving [1:58:15]; Protecting pedestrians: strategies for reducing the risk of fatal accidents with pedestrians on foot or bicycle [2:02:30]; Empowering safe driving: essential resources and tips for parents and teenage drivers [2:14:00]; Promoting a culture of proactive safety: parting thoughts from Mark [2:19:15]; and More.  Connect With Peter on Twitter, Instagram, Facebook and YouTube

#295 ‒ Roadway death and injury: why everyone should care and what you can do to reduce risk | Mark Rosekind, Ph.D.

 View the Show Notes Page for This Episode  Become a Member to Receive Exclusive Content  Sign Up to Receive Peter’s Weekly Newsletter Olav Aleksander Bu is an internationally renowned sports scientist acclaimed for his coaching prowess with elite athletes spanning a diverse range of sports disciplines. In this episode, Olav delves deep into the intricacies of VO2 max and its profound impact on performance. They explore the relationship between VO2 max and ATP production, energy efficiency, and power, as well as the impact of low-intensity training on VO2 max. The conversation extends to Olav’s experiences pushing the boundaries with high-performance athletes and the data driven interventions he uses to improve performance. They also dissect the role of lactate threshold, discuss other important metrics to track, and explore the exciting possibility of utilizing a portable VO2 testing device as a practical alternative to traditional lab-based assessments. We discuss:  Olav’s background, expertise in exercise physiology, coaching experience, and interest in the extremes of human capability [4:15]; The processes of energy conversion within the human body and its implications for performance [9:30]; Improving movement efficiency, and the importance of mindfulness in training to optimize performance [20:00]; The relationship between VO2 max, power output, and endurance performance in different sporting contexts [34:45]; How VO2 max is measured in the lab, and why it’s a crucial predictor of both lifespan and quality of life [44:45]; Absolute vs relative VO2 max, the significance of functional threshold power in cycling, and the importance of longer duration tests for accurate assessments [54:00]; Portable VO2 testing devices as a practical alternative to lab-based tests [1:05:15]; The complexities of measuring ventilation and its impact on performance metrics like VO2 max and heart rate [1:15:45]; Training interventions to increase VO2 max, and factors that impact performance outcomes [1:23:30]; The respiratory exchange ratio (RER) and endurance sports, and how factors such as diet composition and exercise intensity influence RER values and performance [1:32:45]; Science-guided training for versatile athletes: maximizing VO2 max, power, torque, and cadence in cycling, and the importance of incorporating diverse stimuli to enhance performance [1:41:00]; Physiological limitations on VO2 max [2:02:15]; The different energy systems used during work, and other things to monitor like VCO2 and heart rate [2:06:00]; Lactate threshold and other metrics to guide your training [2:10:30]; Analysis of a lactate power curve: exploring lactate dynamics in endurance training and performance [2:23:15]; and More.  Connect With Peter on Twitter, Instagram, Facebook and YouTube  

#09 - David Sabatini, M.D., Ph.D.: rapamycin and the discovery of mTOR — the nexus of aging and longevity?

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