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Zone 2 training: impact on longevity and mitochondrial function, how to dose frequency and duration, and more | Iñigo San-Millán, Ph.D. (#201 rebroadcast)

The Peter Attia Drive

Release Date: 07/08/2024

#385 - AMA #82: Applying the tools of longevity in the real world: disease prevention, DEXA scans, artificial sweeteners, injury recovery, stability training, habit formation, protein intake and mTOR activation, and more show art #385 - AMA #82: Applying the tools of longevity in the real world: disease prevention, DEXA scans, artificial sweeteners, injury recovery, stability training, habit formation, protein intake and mTOR activation, and more

The Peter Attia Drive

In this “Ask Me Anything” (AMA) episode, Peter answers listener questions across a wide range of topics, focusing on practical decision-making and real-world application. He explores how health priorities and strategies should evolve across different decades of life, which chronic diseases are most challenging to manage and how to think about risk hierarchies, and which emerging interventions—beyond exercise—show the most promise for dementia prevention. Peter also breaks down the utility of wearables and explains how to use and interpret DEXA scans effectively. He discusses the...

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#384 - Special episode — Obicetrapib: The CETP inhibitor with cardiovascular benefits and potential Alzheimer's prevention show art #384 - Special episode — Obicetrapib: The CETP inhibitor with cardiovascular benefits and potential Alzheimer's prevention

The Peter Attia Drive

In this special episode, Peter takes a deep dive into obicetrapib, an investigational drug that has captured his attention and renewed interest in an entire class of therapies known as CETP inhibitors. He explains what obicetrapib is and how it works, revisits the history of CETP inhibitors and why earlier versions of these drugs failed—sometimes dramatically—and breaks down the key clinical trials designed to evaluate their impact on cardiovascular risk. Peter examines how obicetrapib influences major lipid biomarkers, including LDL cholesterol and lipoprotein(a) [Lp(a)], and discusses...

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The Peter Attia Drive

Layne Norton is a nutrition scientist and accomplished power athlete,who returns to The Drive for a conversation that departs from the show’s usual format. In this episode, Layne presents the evidence-based case that seed oils are not uniquely harmful under isocaloric conditions, while Peter steelmans the strongest versions of the opposing argument that seed oils are inherently harmful. They examine how scientific bias and evidence are evaluated, revisit the historical randomized controlled trials that shaped the seed oil controversy, and explore the mechanistic biology underlying LDL...

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The Peter Attia Drive

In this “Ask Me Anything” (AMA) episode, Peter brings together his most up-to-date thinking on cardiorespiratory fitness into a single, practical guide designed to help listeners structure training for maximal impact on healthspan, lifespan, and long-term independence. He explains why cardiorespiratory fitness is one of the strongest modifiable predictors of longevity, clarifies what zone 2 training actually represents and how it differs from higher-intensity work, and addresses persistent confusion around exercise volume, intensity, and time constraints. The discussion covers how to...

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The Peter Attia Drive

Abbie Smith-Ryan is a leading researcher in exercise physiology whose work focuses on how training and nutrition influence body composition, metabolism, cardiovascular health, and women’s health across the lifespan, with particular attention on perimenopause and post-menopause. In this episode, Abbie explains how early exercise and play help build the foundation for bone health, muscle development, and cardiorespiratory fitness in girls, as well as how puberty and menstruation shape athletic performance, motivation, and recovery. She also explores how women can tailor training and...

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Building & Changing Habits | James Clear (#183 rebroadcast) show art Building & Changing Habits | James Clear (#183 rebroadcast)

The Peter Attia Drive

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...

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#377 ‒ Special episode: Understanding true happiness and the tools to cultivate a meaningful life—insights from past interviews with Arthur Brooks show art #377 ‒ Special episode: Understanding true happiness and the tools to cultivate a meaningful life—insights from past interviews with Arthur Brooks

The Peter Attia Drive

In this special episode of The Drive, Peter presents a curated “best of” conversation with bestselling author and previous guest Arthur Brooks, organized around four core themes: happiness itself, the forces that undermine it, the tools and practices that help cultivate it, and the courage required to live and love well. The episode brings together the most meaningful moments from two past interviews into a single, focused discussion that distills Brooks’ most insightful ideas and offers practical takeaways for building a life that's both successful and deeply happy. We discuss: ...

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#376 - AMA #78: Longevity interventions, exercise, diagnostic screening, and managing high apoB, hypertension, metabolic health, and more show art #376 - AMA #78: Longevity interventions, exercise, diagnostic screening, and managing high apoB, hypertension, metabolic health, and more

The Peter Attia Drive

In this “Ask Me Anything” (AMA) episode, Peter tackles a wide-ranging set of listener questions spanning lifespan interventions, exercise, cardiovascular risk reduction, time-restricted eating, blood pressure management, hormone therapy, diagnostics, and more. Peter reveals the single most important lever for extending healthspan and lifespan, and explains how he motivates midlife patients using the Centenarian Decathlon framework. He discusses the importance of addressing high apoB and cholesterol even in metabolically healthy individuals with calcium scores of zero, how to manage high...

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The Peter Attia Drive

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The Peter Attia Drive

Carole Hooven is a human evolutionary biologist whose research centers on testosterone, sex differences, and behavior. In this episode, she explores how prenatal testosterone orchestrates male development in the body and brain, how early hormonal surges shape lifelong behavioral tendencies, and what rare natural experiments—such as 5-alpha-reductase deficiency—reveal about the biology of sex differentiation. She discusses distinct male and female aggression styles through an evolutionary lens, how modern environments interact with ancient competitive drives, and the implications of...

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Iñigo San-Millán is an internationally renowned applied physiologist and a previous guest on The Drive. His research and clinical work focuses on exercise-related metabolism, metabolic health, diabetes, cancer metabolism, nutrition, sports performance, and critical care. In this episode, Iñigo describes how his work with Tour de France winner Tadej Pogačar has provided insights into the amazing potential of elite athletes from a performance and metabolic perspective. He speaks specifically about lactate levels, fat oxidation, how carbohydrates in food can affect our lactate and how equal lactate outputs between an athlete and a metabolically unhealthy individual can mean different things. Next, he discusses how Zone 2 training boosts mitochondrial function and impacts longevity. He explains the different metrics for assessing one’s Zone 2 threshold and describes the optimal dose, frequency, duration, and type of exercise for Zone 2. Additionally, he offers his thoughts on how to incorporate high intensity training (Zone 5) to optimize health, as well as the potential of metformin and NAD to boost mitochondrial health. Finally, he discusses insights he’s gathered from studying the mitochondria of long COVID patients in the ICU.

We discuss:

  • The amazing potential of cyclist Tadej Pogačar [2:00];
  • Metrics for assessing athletic performance in cyclists and how that impacts race strategy [7:30];
  • The impact of performance-enhancing drugs and the potential for transparency into athletes’ data during competition [16:15];
  • Tadej Pogačar’s race strategy and mindset at the Tour de France [23:15];
  • Defining Zone 2, fat oxidation, and how they are measured [26:00];
  • Using fat and carbohydrate utilization to calculate the mitochondrial function and metabolic flexibility [35:00];
  • Lactate levels and fat oxidation as it relates to Zone 2 exercise [39:15];
  • How moderately active individuals should train to improve metabolic function and maximize mitochondrial performance [51:00];
  • Bioenergetics of the cell and what is different in elite athletes [56:30];
  • How the level of carbohydrate in the diet and ketogenic diets affects fuel utilization and power output during exercise [1:07:45];
  • Glutamine as a source for making glycogen—insights from studying the altered metabolism of ICU patients [1:14:15];
  • How exercise mobilizes glucose transporters—an important factor in diabetic patients [1:20:15];
  • Metrics for finding Zone 2 threshold—lactate, heart rate, and more [1:24:00];
  • Optimal Zone 2 training: dose, frequency, duration, and type of exercise [1:40:30];
  • How to incorporate high intensity training (Zone 5) to increase VO2 max and optimize fitness [1:50:30];
  • Compounding benefits of Zone 2 exercise and how we can improve metabolic health into old age [2:01:00];
  • The effects of metformin, NAD, and supplements on mitochondrial function [2:04:30];
  • The role of lactate and exercise in cancer [2:12:45];
  • How assessing metabolic parameters in long COVID patients provides insights into this disease [2:18:30];
  • The advantages of using cellular surrogates of metabolism instead of VO2 max for prescribing exercise [2:25:00];
  • Metabolomics reveals how cellular metabolism is altered in sedentary individuals [2:33:00];
  • Cellular changes in the metabolism of people with diabetes and metabolic syndrome [2:38:30]; and
  • More.

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