The Human Upgrade: Biohacking for Longevity & Performance
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PodcastThe Human Upgrade: Biohacking for Longevity & Performance
Publisher/creatorDave Asprey
Shortcast updated
About this episode
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. Watch this episode on YouTube for the full video experience: https://www.youtube.com/@DaveAspreyBPR 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 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 is the top podcast for people who want to take control of their biology, extend their longevity, and optimize every system in the body and mind. Each episode features cutting edge insights in health, performance, neuroscience, supplements, nutrition, hacking, emotional intelligence, and conscious living. Thank you to our sponsors! • BEYOND Conference 2026 | Register now with code DAVE300 for $300 off at https://beyondconference.com/ • AquaTru | Go to https://aquatruwater.com/daveasprey and save $100 on all AquaTru water purifiers. • Caldera + Lab | A small habit with big results. Go to https:// CalderaLab.com/ DAVE and use code DAVE for 20% off your first order. • Timeline | Go to https:// timeline.com/Dave for 20% off. 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: • Learn More About Valter’s Work At: https://valterlongo.com/ • Join My Fasting Challenge: https://daveasprey.com/#14-day • Get My 2026 Biohacking Trends Report: https://daveasprey.com/2026-biohacking-trends-report/ • Join My Low-Oxalate 30-Day Challenge: https://daveasprey.com/2026-low-ox-reset/ • 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 Timestamps: 0:00 Introduction & Aging Fundamentals 4:36 Fasting Mimicking Diet Overview 7:03 Insulin, IGF-1 & mTOR 11:03 Body Fat & Fasting Frequency 17:08 The Protein Debate 20:22 Blue Zones & Centenarian Evidence 23:10 Amino Acids & Leucine 30:30 Growth Hormone & Longevity 34:01 Five-Day Fasting Benefits 40:55 Personalization & AI 42:29 Plant-Based Concerns 49:07 Fasting Risks & Limits 53:05 Supplements & Equilibrium 1:03:05 Ranking Longevity Pathways 1:05:05 Modern Environmental Challenges 1:16:21 Final Thoughts See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info .
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Episode summary
You’re listening to The Human Upgrade. I’m excited to dig into fasting, intermittent fasting, and longevity with Dr. Valter Longo, one of the most studied experts on how not eating for a bit changes the body—what do most people still get wrong about aging?
We chase quick wins and forget the long game. GLP-1 drugs look great short term, but when you stack them against a Mediterranean or longevity-style diet that includes time-restricted eating, periodic fasting-mimicking cycles, movement, and sleep, the diet wins over years; we’re now testing three to four fasting-mimicking rounds per year in a large Italian study.
For people new to this, ProLon is your fasting‑mimicking diet in a box that makes a five‑day fast doable. Why does it work while you’re still eating?
Because it triggers a coordinated, evolved program: organs temporarily downsize, stem cells activate, and cells flip on reprogramming factors in organ‑specific ways. You get regeneration signals without the collateral damage that can come from forcing the same pathways with drugs.
Can you lay out insulin and mTOR for listeners and what fasting does to them?
Fasting cycles lower insulin and IGF‑1 and dial down mTOR, a growth switch tied to protein synthesis. High mTOR keeps you in growth mode, which supports size but also accelerates aging.
But we still need muscle. How do you balance growth and regeneration?
You need a minimum growth signal for muscle synthesis, and very low protein—especially mostly plant—can drop mTOR too far. In our trials, fasting‑mimicking cycles preferentially reduce fat, protect lean mass, and sometimes bump it up, likely via satellite cell activation.
If someone’s very lean with good muscle, should they fast less?
Be cautious and do it less often until we know more, especially as you age, since some fat reserve can be protective. The real goal is equilibrium, not extremes.
Protein is polarizing. I feel better around two point two grams per kilo, but you recommend much lower. How do we square that?
A century of data points to protein restriction extending rodent lifespan, and human epidemiology links high animal protein to diabetes, obesity, and cardiovascular mortality. Longevity cultures trend low on protein with more plant sources, and we should focus less on “protein” and more on amino acid profiles, because leucine and methionine drive growth pathways differently.
What about protein absorption speed and meal timing?
For muscle growth, timing matters more—hit a quality dose around training to reach the leucine threshold for synthesis. In general, around zero point eight grams per kilo per day balances disease risk with function, but trade‑offs vary by age and goals.
Is there a best daily leucine target for longevity?
Lower leucine supports lifespan in animals but can raise frailty, so the sweet spot depends on age, muscle status, and disease risk; Okinawan patterns were very low on total amino acids, including leucine, alongside exceptional longevity.
If I eat a steak, can I blunt the growth signal cost?
We’re exploring oral growth hormone receptor inhibitors, since blocking that axis extends lifespan in mice and protects humans with similar mutations, but aging isn’t yet an approval path and complex food‑based regimens don’t fit current FDA lanes.
Many listeners do cyclical keto or eighteen-hour fasts. What does a five‑day fasting‑mimicking cycle add?
Time. Around five days lets autophagy and reprogramming mount across tissues, then refeeding carries regeneration forward for days to weeks; it’s a shrink‑and‑rebuild wave that’s hard to mimic with shorter windows.
I agree fasting is the biggest lever, with circadian alignment close behind.
Circadian hygiene matters, but five days of fasting rewires gene expression across organs in a way light and timing don’t match on that timescale.
Personalization keeps growing. Can AI help tailor diet and fasting, and what about oxalates for plant‑forward eaters?
AI plus clinician science will speed customization, and our clinics already mix the longevity diet with fasting‑mimicking to unlock stubborn insulin resistance. Big‑picture data still lifts legumes and olive oil for healthy aging, but we do elimination protocols for the one‑in‑four or so who react; stick to traditional foods your family tolerated and personalize from there.
Can fasting go too far, and how should people think about dose?
Treat it like medicine: who, when, how long. Very long fasts can trigger hypometabolism and gut leakiness in animals, while our five‑day format with specific composition avoided that and reduced risks like hypotension and hypoglycemia; the safest path is tested protocols, not improvised extremes.
Can you rank the longevity pathways you’ve worked on?
The growth hormone receptor axis is the master lever, with mTOR next, especially in later life; fasting‑mimicking modulates GH/IGF‑1, insulin, mTOR, and PKA together. The pattern that works is alternating low signals for cleanup with higher signals on refeed for rebuilding.
Water fasts can make the gut leaky, which is why I like ProLon’s approach that includes things like glycerol to protect muscle and mimic fasting biochemistry.
Glycerol rises naturally during fasting, so we include it, plus prebiotic foods that echo long‑lived cultures; I donate my proceeds so people know this isn’t about profit.
What about creatine and other supplements that boost performance now?
Mega‑dosing single molecules can disturb a finely tuned equilibrium built over evolution; I look for multi‑pillar evidence of lifespan extension rather than short‑term benefits alone, and creatine doesn’t yet have that longevity signal.
We don’t live in a natural environment, so I use targeted tools for function while we wait for better data; big real‑world datasets and AI should soon reveal who benefits from what.
I agree, as long as the inputs are high‑quality and filtered; with the right team plus AI, personalization will scale fast.
Last one: should some people suppress growth hormone to live longer?
If your growth axis runs high—think IGF‑1, insulin, mTOR—bringing it into an optimal range likely helps; I can see a future where we track IGF‑1 like cholesterol and treat to a healthy band.
Thanks for the work you’ve done and for innovating a practical way to fast. I’ll experiment with lower protein when travel calms down, and I’ll keep using ProLon as a tool; see you next time on The Human Upgrade.
This show is informational and not medical advice; talk with your healthcare provider before acting on what you hear.
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