The Human Upgrade: Biohacking for Longevity & Performance

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What it takes to be “Young Forever!” | Mark Hyman : 1385

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Dec 23, 2025

Guest

Mark Hyman

Mark Hyman, a leading physician in functional medicine and author of *Young Forever*, joins to discuss the biology of aging. He explains how insulin signaling, mTOR, and mitochondrial health play crucial roles in reversing biological age. Mark reveals that sugar can accelerate aging more than protein and debunks myths surrounding protein and carnivore diets. With real-life examples of patients reversing diseases through lifestyle changes, he emphasizes the importance of metabolic flexibility and treating root causes for optimal health.

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ANECDOTE

Diet Reversed Advanced Disease

Janice reversed severe diabetes, heart failure, fatty liver and lost 116 pounds after dietary changes.
She went off insulin in three days and off all medications in three months.

insights

INSIGHT

Nutrient Sensing Is The Meta-Hallmark

Deregulated nutrient sensing is a meta-hallmark that triggers other hallmarks of aging.
Four key pathways (insulin, mTOR, AMPK, sirtuins) coordinate aging responses.

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ADVICE

Lifestyle Often Outperforms Drugs

Prioritize lifestyle interventions over longevity drugs; diet and exercise outperform drugs like metformin for many outcomes.
Use medications only when needed and compare them to strong lifestyle approaches.

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Why Mark Wrote Young Forever

02:15 • 2min

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Measuring Biological Age

04:00 • 1min

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Hallmarks of Aging and Functional Medicine

05:28 • 2min

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A Patient Reversed Advanced Disease

07:32 • 2min

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Longevity Switches and Systems Thinking

09:12 • 2min

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Insulin: A Central Driver of Aging

11:20 • 9min

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Protein, mTOR and Metabolic Flexibility

20:43 • 3min

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AMPK, Sirtuins, NAD and Metformin

23:24 • 2min

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How Pathways Regulate Mitochondria

25:20 • 3min

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Lifestyle vs Drugs for Diabetes

28:27 • 1min

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GLP-1 Drugs, Muscle Loss, and Tradeoffs

29:42 • 4min

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Rapamycin and Calorie-Restriction Mimetics

33:16 • 6min

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Mark's Rapamycin Use and Fasting

39:21 • 5min

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How to Stimulate Muscle Protein Synthesis

44:10 • 2min

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Sugar Raises mTOR More Than Protein

46:32 • 1min

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Body Composition, DEXA Insights

47:41 • 2min

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Metabolic Flexibility and Meal Timing

49:27 • 3min

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Optimal Protein Intake Recommendations

52:25 • 3min

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Healthy Aging vs Anti-Aging Framing

55:00 • 3min

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Inflammation as a Central Hallmark

58:29 • 2min

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Senescent Cells and Therapies

01:00:36 • 1min

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Mast Cells, Immune Sensitivity, and Allergies

01:01:52 • 3min

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Practical Takeaways and Book Plug

• Mentioned in 89 episodes

Smarter Not Harder

The Biohacker's Guide to Getting the Body and Mind You Want

Dave Asprey

In 'Smarter Not Harder,' Dave Asprey exposes the surprising secrets of the body's operating system, or 'MeatOS,' which is naturally designed to be lazy. He shows how to hack this system to achieve optimum wellness by exercising and eating smarter, not harder, and utilizing the body's built-in laziness. The book is packed with practical information on better eating, smart workouts, and strategic therapies to reduce stress and boost resilience, aiming to upgrade metabolic, neurological, and epigenetic systems.

#7798

• Mentioned in 6 episodes

Super Human

The Bulletproof Plan to Age Backward and Maybe Even Live Forever

Dave Asprey

In 'Super Human,' Dave Asprey presents a revolutionary approach to anti-aging, showing how it is possible to make changes on the sub-cellular level to dramatically extend life span. The book is divided into three parts: 'Don't Die,' which identifies the Four Killers (heart disease, diabetes, Alzheimer’s, and cancer); 'Age Backward,' which provides methods to reverse aging; and 'Heal Like a Deity,' which offers strategies to heal faster. Asprey’s research and personal experiences are used to provide practical advice on diet, sleep, light, exercise, and other little-known hacks to decelerate cellular aging and enhance overall health and performance.

#4519

• Mentioned in 11 episodes

Food

What the Heck Should I Eat?

Mark Hyman

In this book, Dr. Mark Hyman clarifies the confusion surrounding nutrition by examining every food group and debunking common misconceptions. He provides a roadmap for achieving lifelong health through whole foods and explains how food impacts personal health, the environment, and society. The book offers practical advice and recipes to help readers make healthier choices.

#198

• Mentioned in 115 episodes

Heavily Meditated

8 Steps to Remove Your Triggers and Upgrade Your Mind

Dave Asprey

In 'Heavily Meditated', Dave Asprey combines ancient wisdom traditions and practices with modern technology and cutting-edge methods. The book is based on his immersive program '40 Years of Zen' and provides an 8-step approach to help readers remove their triggers and upgrade their mental well-being. Asprey draws on his extensive experience in biohacking and human performance optimization to offer practical advice for improving mental clarity and resilience.

#176

• Mentioned in 126 episodes

Young Forever

The Secrets to Living Your Longest, Healthiest Life

Mark Hyman

In *Young Forever*, Dr. Mark Hyman challenges readers to reimagine their biology, health, and the process of aging. The book explores the biological hallmarks of aging, their causes, and their consequences, and provides simple dietary, lifestyle, and emerging longevity strategies to overcome them. It covers topics such as turning on longevity switches, reducing inflammation, supporting the immune system, exercising, sleeping, and de-stressing for healthy aging, and features Dr. Hyman's Pegan Diet. The book aims to help readers increase their health span, prevent and reverse diseases like heart disease, cancer, diabetes, and dementia, and live a longer, healthier life.

Most conversations about longevity focus on tactics. This episode breaks down the biology underneath them. You’ll hear a systems level analysis of how insulin signaling, mTOR, mitochondrial function, inflammation, and nutrient sensing interact to determine biological age, disease risk, and long term human performance. This is not surface level biohacking. It is a deep dive into the mechanisms that actually control aging, metabolism, muscle preservation, and brain optimization, and why most anti aging strategies fail when they ignore these foundations.

This all-time classic episode from 2024, has host Dave Asprey joined by Mark Hyman, a practicing physician and one of the most respected leaders in functional medicine. Dr. Hyman is the founder and senior advisor of The UltraWellnessCenter, the founder and former head of strategy and innovation at the Cleveland Clinic Center for Functional Medicine, and a long time advocate for treating root causes instead of managing disease. With over 30 years of clinical experience, his work focuses on restoring mitochondrial health, optimizing metabolism, reversing chronic disease, and slowing biological aging using science backed interventions.

Together, Dave and Mark dismantle common myths around protein, carnivore diets, ketosis, fasting, supplements, and longevity drugs. They explain why sugar accelerates aging faster than protein, how mTOR must cycle instead of staying suppressed, and why muscle, mitochondria, and metabolic flexibility matter more than calorie restriction. The conversation also covers nootropics, sleep optimization, neuroplasticity, AI driven diagnostics, and how functional medicine reframes aging as a reversible biological process rather than an inevitable decline.

You’ll learn:

• How insulin and nutrient sensing control aging speed

• Why mitochondria sit at the center of longevity and disease

• The truth about mTOR, fasting, and protein intake

• How ketosis and metabolic flexibility protect long term health

• Where supplements and nootropics actually fit in brain optimization

• Why functional medicine outperforms symptom based care

• How AI and advanced testing are reshaping modern medicine

Thank you to our sponsors!

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Dave Asprey is a four-time New York Times bestselling author, founder of Bulletproof Coffee, and the father of biohacking. With over 1,000 interviews and 1 million monthly listeners, The Human Upgrade brings you the knowledge to take control of your biology, extend your longevity, and optimize every system in your body and mind. Each episode delivers cutting-edge insights in health, performance, neuroscience, supplements, nutrition, biohacking, emotional intelligence, and conscious living.

New episodes are released every Tuesday, Thursday, Friday, and Sunday (BONUS). Dave asks the questions no one else will and gives you real tools to become stronger, smarter, and more resilient.

Keywords: longevity biohacking, functional medicine longevity, biological age reversal, mitochondria and aging, mTOR pathway aging, insulin resistance and aging, metabolic flexibility, fasting and longevity, ketosis and metabolism, protein intake and mTOR, muscle and longevity, inflammaging, chronic inflammation aging, mitochondrial dysfunction, nutrient sensing pathways, rapamycin longevity, metformin longevity debate, carnivore diet longevity, sugar and aging, brain optimization longevity, neuroplasticity and aging, sleep optimization biohacking, supplements for longevity, anti aging metabolism, human performance optimization, Dave Asprey longevity, Mark Hyman longevity

Resources:

• Mark’s Website: https://drhyman.com/

• Dave Asprey's Latest News | Go to https://daveasprey.com/ to join Inside Track today.

• Danger Coffee: https://dangercoffee.com/discount/dave15

• My Daily Supplements: SuppGrade Labs (15% Off)

• Favorite Blue Light Blocking Glasses: TrueDark (15% Off)

• Dave Asprey’s BEYOND Conference: https://beyondconference.com

• Dave Asprey’s New Book – Heavily Meditated: https://daveasprey.com/heavily-meditated

• Upgrade Collective: https://www.ourupgradecollective.com

• Upgrade Labs: https://upgradelabs.com

• 40 Years of Zen: https://40yearsofzen.com

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