EP 1373
1373. STOP Intermittent Fasting If You Want to Stay Young
In this episode of The Human Upgrade, Host Dave Asprey sits down with Valter Longo for a systems-level conversation on fasting, protein, and aging that challenges popular biohacking assumptions. They explore why intermittent fasting can backfire when applied without proper duration and refeeding, how short-term health gains often mislead long-term longevity outcomes, and why amino acids, mTOR, IGF-1, and growth hormone signaling shape mitochondrial health, neuroplasticity, and lifespan. The discussion spans fasting-mimicking diets, ketosis, metabolism, muscle preservation, Blue Zone evidence, supplements, and nootropics, while also examining modern stressors and AI-driven personalization as the next frontier in functional medicine and Smarter Not Harder longevity strategies.
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In this Episode of The Human Upgrade™...
STOP intermittent fasting if you think it automatically keeps you young. In this episode, you’ll learn why short-term fasting results can mislead long-term aging outcomes, and how duration, frequency, refeeding, and protein intake determine whether fasting supports longevity or quietly accelerates decline.
Host Dave Asprey sits down with Valter Longo, one of the world’s leading longevity researchers with over 30 years of experience studying aging, nutrition, and disease prevention. Dr. Longo is the Director of the Longevity Institute at the University of Southern California’s Leonard Davis School of Gerontology and the Director of the Longevity and Cancer Program at IFOM, the Italian Foundation for Cancer Research Institute of Molecular Oncology in Milan. He is the author of the bestselling book The Longevity Diet and was named one of TIME Magazine’s 50 most influential people in health care for his research on fasting-mimicking diets.
Together, Dave Asprey and Dr. Longo explain why many people focus too heavily on short-term effects and extrapolate them incorrectly across a lifetime. They break down how intermittent fasting differs biologically from multi-day fasting, why five-day fasting cycles trigger deeper cellular changes, and how insulin, IGF-1, mTOR, and growth hormone shape aging, regeneration, and disease risk over time.
The conversation covers protein and amino acid intake, muscle preservation, frailty risk, and the tradeoffs between strength, function, and longevity. They explore ketosis, fasting-mimicking diets, stem cell activation, mitochondrial function, neuroplasticity, and why equilibrium and cycling matter more than constant restriction. Dave and Valter also discuss supplements, nootropics, creatine, carnivore-style eating, metabolism, sleep optimization, and how AI may eventually personalize fasting and nutrition based on individual biology rather than population averages.
You’ll learn:
- Why short-term fasting benefits do not predict long-term longevity
- How fasting duration changes gene expression and cellular regeneration
- The difference between intermittent fasting and multi-day fasting
- How protein and amino acids influence mTOR, IGF-1, and aging
- Why muscle, strength, and longevity must be balanced, not maximized
- When ketosis overlaps with fasting and when it does not
- Why supplements can disrupt biological equilibrium
- How AI could support future personalization in fasting and nutrition
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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: intermittent fasting longevity, fasting mimicking diet, fasting and aging science, biohacking fasting podcast, longevity fasting research, protein restriction longevity, amino acids aging, mTOR IGF-1 longevity, mitochondria aging science, neuroplasticity fasting, ketosis fasting science, metabolism longevity podcast, anti-aging fasting, functional medicine longevity, supplements fasting debate, nootropics brain optimization, muscle frailty aging, sleep optimization longevity, AI personalized nutrition, carnivore diet longevity debate, Dave Asprey fasting, Valter Longo longevity, longevity diet podcast, human performance aging
Resources:
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“If you look at a hundred years of data, the only intervention to make mice and rats consistently live longer is protein restriction.”
Valter Longo
0:00 Introduction & Aging Fundamentals
Dave explains why short-term health results often fail to predict long-term aging outcomes and sets the framework for thinking in decades, not weeks.
4:36 Fasting Mimicking Diet Overview
Valter Longo outlines how the fasting mimicking diet works, why it differs from intermittent fasting, and how it compares to Mediterranean-style longevity diets.
7:03 Insulin, IGF-1 & mTOR
They break down the core longevity pathways that regulate growth, aging, and muscle synthesis, including insulin, IGF-1, and mTOR signaling.
11:03 Body Fat & Fasting Frequency
A discussion on optimal body fat levels, why being too lean can backfire, and when certain people should fast less frequently.
17:08 The Protein Debate
Dave and Valter explore high versus low protein intake, short-term performance gains, and long-term risks for aging and disease.
20:22 Blue Zones & Centenarian Evidence
Valter shares insights from long-lived populations and what their dietary patterns reveal about protein, plants, and longevity.
23:10 Amino Acids & Leucine
They explain why amino acid profiles matter more than total protein, with a focus on leucine and aging pathways.
30:30 Growth Hormone & Longevity
A deep dive into growth hormone receptors as a master regulator of lifespan, healthspan, and disease risk.
34:01 Five-Day Fasting Benefits
Why multi-day fasting cycles trigger deeper regeneration, stem cell activation, and cellular reprogramming than shorter fasts.
40:55 Personalization & AI
How AI and large data sets could personalize fasting, protein intake, and longevity strategies based on individual biology.
42:29 Plant-Based Concerns
Addressing oxalates, anti-nutrients, and why some people struggle with certain plant foods despite population-level benefits.
49:07 Fasting Risks & Limits
When fasting goes too far, including risks of overdoing restriction, gut issues, and metabolic adaptation.
53:05 Supplements & Equilibrium
A critical look at supplements like creatine, growth factors, and how megadosing can disrupt biological balance.
1:03:05 Ranking Longevity Pathways
Valter stack-ranks the most important aging pathways, including growth hormone, mTOR, insulin, and IGF-1.
1:05:05 Modern Environmental Challenges
Dave discusses microplastics, EMFs, travel, and modern stressors that complicate achieving biological equilibrium.
1:16:21 Final Thoughts
Closing reflections on protein experimentation, personalization, and how to balance performance with longevity over a lifetime.
Enjoy the show!
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