The Human Upgrade: Biohacking for Longevity & Performance

Host: Dave Asprey
Guest: Dr. Valter Longo (Professor of Gerontology and Biological Sciences, Director of the Longevity Institute at USC)
Episode: STOP Intermittent Fasting If You Want to Stay Young : 1409
Date: February 3, 2026

Episode Overview

This episode dives deep into the science and misconceptions of fasting, protein intake, and nutritional strategies for longevity. Dave Asprey interviews Dr. Valter Longo—widely recognized for his research on aging, fasting, and the “longevity diet.” They discuss long-term versus short-term health interventions, the power (and pitfalls) of fasting, optimal protein consumption, the personalization of diets for longevity, and how emerging tools like AI will shape future nutritional recommendations.

Key Topics and Insights

1. Short-Term Versus Long-Term Interventions

• Misconception: Most people fixate on immediate results, projecting short-term benefits into long-term outcomes, which is "dangerous and usually wrong."
  • “Short-term effects and long-term consequences are very, very different.” — Dr. Longo [00:00, 03:43, 74:15]
• Example: GLP-1 drugs may help with weight and immediate cardiovascular risk, but traditional dietary interventions like the Mediterranean or longevity diet are much more effective for lifespan.

2. The Power of the Longevity Diet and Fasting Mimicking Diet (FMD)

• Fasting Mimicking Diet: Developed by Dr. Longo, allows for eating while still inducing cellular regeneration and longevity pathways.
  • Mechanisms: Increased stem cells, activation of Yamanaka factors (rejuvenate old cells), tissue/organ regeneration.
    • “In some cases, it’s an increase of stem cells…in some other cases it’s reprogramming cells.” — Dr. Longo [06:43]
• Why FMD Works: Multi-organ benefits in mice, rats, and humans; coordinated evolutionary process with fewer drawbacks than forced cellular reprogramming.
• Practical Use: 5 days every 3–4 months promotes benefits without excessive restriction.

3. Protein Intake Myths and Data

• Optimal Protein: Debate around minimum requirements versus longevity.
  • “If you look at 100 years of data… the only intervention to make mice and rats consistently longer-lived is protein restriction.” — Dr. Longo [00:00, 19:46]
• Plant vs Animal Protein: High animal protein intake correlates with more diabetes, obesity, and cardiovascular disease in epidemiological studies.
• Notable Outlier (Hong Kong): High meat intake, high longevity. Dr. Longo dismisses it as an insufficient counterpoint to overwhelming multi-pillar evidence.
  • “You could say ‘what if,’ but you need another 100 years of similar data to counterbalance that.” — Dr. Longo [22:08]

4. Personalized Longevity Nutrition

• Individual Biology: Recommendations may change based on genetics, ancestry, and personal biology (e.g., Asprey’s Basque background and protein tolerance).
  • “There could be people that need another level of proteins… but seems to be fairly consistent.” — Dr. Longo [43:31]
• AI & Data: The future points to AI-driven personalized diets optimizing longevity, healthspan, and disease-risk factors.
  • “AI is just going to probably do a much better job… than even we can do with lots of scientists and physicians.” — Dr. Longo [45:42]

5. Balance: Muscle Mass, Leanness, and Fat

• Risks of Excess Leanness (Especially in Older Age):
  • “Older people that have a little more fat reserves… tend to do better.” — Dr. Longo [14:10]
• Muscle Maintenance: FMD and well-designed low-protein diets can preserve or even increase lean mass while targeting fat loss.

6. Nutrient Timing, Amino Acids, and Quality

• More Than Protein Amount: Focus on amino acid profile and timing for muscle synthesis (leucine especially relevant).
• Application: Regular, moderate protein intake (0.8g/kg) for most; adjust for age, muscle, and goals.

7. Systemic Equilibrium and Supplements

• Caution Against Mega-dosing: Evolution shaped a delicate equilibrium—overdosing on anything (even 'beneficial' supplements) likely disrupts it.
  • “As you mega dose anything… you’re going to disrupt this equilibrium.” — Dr. Longo [65:46]
• Supplements like Creatine: Short-term benefits are possible, but if not supported by longevity or epidemiological data, they should be viewed with skepticism.

8. Fasting: Not Always "More Is Better"

• Risks of Over-Fasting:
  • Water-only fasting beyond a few days can cause leaky gut, hypoglycemia, and is tough to sustain.
  • “I hate the word fasting. I always say, it’s eating. Is eating good for you or bad for you? It’s pointless.” — Dr. Longo [53:54]
  • Fasting must be individualized (“dose, who, when”) to avoid harm; most people will overdo or do it unsafely without guidance.

9. Growth Hormone, IGF-1, mTOR, and Longevity Pathways

• Hierarchy of Impact:
  • #1 Growth Hormone Receptor, #2 mTOR.
  • “Growth hormone is clearly the most powerful… modulator of lifespan.” — Dr. Longo [58:09]
• Alternation of States: The combination of low and high states (via fasting and refeeding) is physiologically vital.

10. Oxalate, Beans, and Food “Toxicities”

• Don’t Discard Longevity Foods (e.g., legumes) Because of Isolated Compounds:
  • Epidemiology indicates net positive effects except in specific intolerant/predisposed populations.
  • “If this ingredient is bad for most, why do we see such positive results in large cohorts?” — Dr. Longo [47:48]

Notable Quotes & Memorable Moments

• On Protein and Longevity:
  • “If you look at 100 years of data… the only intervention to make mice and rats consistently longer-lived is protein restriction.” — Longo [00:00, 19:46]
• On AI & Personalization:
  • “AI is going to do a much better job than even lots of scientists and physicians.” — Longo [45:42]
• On Fasting as Drug:
  • “FMD is, we think of it as a drug made of food.” — Longo [62:07]
• On the Future:
  • “I’m hopeful… very close to the golden age of personalized longevity.” — Asprey [76:42]
• On Longevity vs. Acute Performance:
  • “Function, strength and longevity, they’re very closely connected.” — Longo [73:14]
• “Short-term effects and long-term consequences are very, very different.” — Longo [74:15]
• “I hate the word fasting… For whom? When? Otherwise we probably do more damage than good.” — Longo [53:54]
• “You could have something extremely effective short term… and then, you know, eventually it might help you a lot less than something else.” — Longo [03:43]
• “Pick the foods your grandparents ate all the time. That’s what you’ll do best with.” — Longo [51:52]

Key Timestamps for Important Segments

| Timestamp | Segment & Topic | |-----------|------------------------------------------------------------------| | 00:00–01:08 | Dr. Longo on short vs. long-term effects and protein restriction | | 03:33–04:39 | Biggest misconceptions in aging science | | 06:11–06:43 | "Why does fasting mimicking diet work?" | | 08:25–10:09 | Fasting’s effect on insulin, IGF-1, mTOR pathways | | 14:10–15:40 | The risks of excessive thinness and body fat in aging | | 19:46–24:03 | Data on optimal protein intake & animal vs. plant protein | | 26:19–27:32 | Protein timing & absorption discussion | | 29:45–31:18 | Leucine, amino acids, and protein recommendations | | 38:49–41:17 | Why 5-day FMD works vs. intermittent fasting/ketosis | | 53:54–56:08 | The dangers of un-contextualized fasting | | 57:53–60:48 | Ranking of longevity pathways: Growth hormone, mTOR, IGF-1 | | 62:07–65:21 | Water fasting risks and rationale for FMD/Prolon | | 70:47–73:14 | Equilibrium, biohacking, and supplement caution | | 74:00–75:06 | Growth hormone and long-term effects | | 76:42–78:05 | The future of personalized longevity via AI |

Tone & Takeaways

• Pragmatic and evidence-driven: Dr. Longo cautions against over-interpreting trends, encourages multi-pillar, longitudinal analysis.
• Personalization & nuance: There’s no “one-size-fits-all” solution—context, age, ancestry, and goals matter.
• Equilibrium over excess: Biohacking should seek to restore, not radically disrupt, the evolved balance of the human body.
• Fasting is powerfully beneficial when applied properly—but more isn’t always better.

Recap for Non-Listeners

This episode arms you with a deep, science-based understanding of why simplistic or dogmatic approaches to fasting, protein, or supplements fail the test of longevity science. Dr. Longo’s advice: combine evidence from many domains; personalize interventions with new tools; and don’t let short-term gains compromise your future resilience and health. The Fasting Mimicking Diet emerges as a well-studied, sustainable fasting strategy. The episode finishes on an optimistic note about AI’s potential to unlock a new era of truly individualized longevity protocols.