The Human Upgrade™ with Dave Asprey

Episode 1385: “What it takes to be ‘Young Forever!’ | Mark Hyman”
Date: December 23, 2025
Guest: Dr. Mark Hyman
Host: Dave Asprey

Episode Overview

This episode dives deeply into the science and practice of longevity, focusing on the actionable, root-cause approaches to aging–or more precisely, “healthy and optimal aging”—with functional medicine pioneer Dr. Mark Hyman. The conversation covers the hallmarks and causes of biological aging, how to reverse or slow them, the nuanced role of nutrition (especially protein), critical lifestyle interventions, and the latest perspectives on anti-aging pharmaceuticals like metformin and rapamycin. The tone is dynamic, direct, and practical—often blending biohacker enthusiasm with scientific nuance and a healthy dose of humor.

Key Themes & Discussion Points

1. Paradigm Shift: Viewing Aging as a Disease (06:17, 07:00)

• Aging Reframed: Hyman advocates seeing rapid biological aging as an abnormal and largely treatable process, not inevitable decline.
  • “We have now finally unlocked the causes of rapid biological aging, which is abnormal and it's treatable. So all of a sudden we're kind of reframing aging as a disease.” — Mark Hyman (05:02)
• Functional Medicine Lens: Rather than managing diseases downstream, focus on creating health and restoring optimal function at the source.

2. Measuring Biological Age & Interventions (04:00, 05:02)

• Objective Markers: DNA methylation clocks, telomere measurements, and DEXA scans are discussed for tracking biological age.
  • “I'm chronologically 63, but I'm biologically 43 because I've applied a lot of these principles to myself.” — Mark Hyman (03:51)
• Actionable Programs: Interventions can “reprogram our biology and our genes” toward a younger state.

3. Hallmarks & Root Causes of Aging (09:41, 10:09, 18:07)

• Hallmarks of Aging: Discussion of 10-13 interconnected biological systems/pathways that collectively drive aging, e.g., mitochondrial dysfunction, deregulated nutrient sensing, inflammaging, cellular senescence.
  • “It's not really separate. They're not like, oh, it's 10 different things or 13 different things. It's really one system.” — Mark Hyman (10:09)
• Functional Medicine Approach: Treat root causes (the “cause of the hallmarks”) rather than merely symptoms or surface-level biomarkers.

4. Nutrient Sensing & Longevity Switches (18:33, 18:53, 22:00, 25:19, 43:16)

• Four Key Pathways:
  • Insulin Signaling: Too much insulin is devastating for aging; fasting insulin is a crucial, overlooked diagnostic marker.
    • “Too much insulin is the worst thing you could possibly think of for aging.” — Mark Hyman (18:53)
  • mTOR: Regulates growth/protein synthesis; needs cyclic inhibition for autophagy and longevity.
    • “MTOR is a really interesting pathway...If you don't give yourself a break from eating, you can't give this pathway a rest.” — Mark Hyman (22:00)
  • AMPK/Sirtuins: Pathways activated by fasting, nutrient scarcity; linked to cellular cleanup, DNA repair, and mitochondrial function.
• Integrated Systems: Metabolic flexibility is more important than any specific dietary dogma.

5. Food, Protein & the mTOR Debate (46:23, 41:11, 44:16)

• Nuanced Meat/Protein Discussion:
  • Quality and timing matter; cyclic mTOR activation is crucial for muscle maintenance as we age.
    • “So the idea that if you overstimulate mtor, you're going to age faster is true. So logically, if you eat anything that stimulates mtor, that's bad. Well, that's wrong, right? It's like Goldilocks. You need just the right amount at the right way.” — Mark Hyman (43:16)
  • Sugar (refined carbs) is a far more potent and harmful stimulator of mTOR than animal protein.
    • “Literally, if you’re restricting animal protein because cancer and you’re having any sugar at all, you’re doing it wrong, because sugar is way stronger than animal protein at raising mtor.” — Dave Asprey (46:48)
  • Protein intake: Most people need more and higher-quality protein, especially after fasting, to preserve muscle.
    • “You need a big load of protein in a fasted state so that you actually activate MTOR in that way after fasting. That's the best way to build muscle.” — Mark Hyman (50:01)

6. Lifestyle Interventions vs. Pharmaceuticals (25:54, 27:56, 29:59)

• Metformin: Cautioned against as a blanket longevity drug; it underperforms compared to lifestyle and diet changes.
  • “There's no more powerful drug. So I'm just saying, like, you can give every diabetic every drug, every treatment that is conventional for diabetes. You will never reverse it...But with food, you can go away in three days.” — Mark Hyman (28:44)
• GLP-1 Agonists/Ozempic: Useful in select cases for weight loss, but cause significant muscle loss and require aggressive lifestyle changes to prevent weight regain.
  • “When you take ozempic, 40% of the weight loss is muscle.” — Mark Hyman (31:08)
• Rapamycin: Potentially promising for cycling mTOR inhibition and longevity, if used judiciously, but much remains to be studied.

7. Inflammation and Inflammaging (56:05, 61:04)

• Root of Chronic Disease: All age-related diseases are, at their root, inflammatory.
  • “Heart disease, cancer, diabetes, Alzheimer's, depression, obviously autoimmune disease, all these are inflammatory diseases.” — Mark Hyman (56:05)
• Zombie Cells (Senescent Cells): Key contributors to “inflammaging”; therapies include senolytics like fisetin and lifestyle interventions.
• Diagnostic Progress: Research points toward novel biomarkers for systemic inflammation, with AI-driven “immunomes” able to predict mortality.
• Lifestyle Impacts: Hyperbaric oxygen therapy shown to be effective at reducing senescent cells.

8. Metabolic Flexibility and Individualization (49:26)

• Key to Health: Greater health comes from a body that can adapt to various inputs, not from rigid avoidance or elimination.
  • “Health is about metabolic flexibility and resilience. Most of us are metabolically inflexible…” — Mark Hyman (49:26)
• Personalization: Dietary needs and effects vary widely by individual; “one size fits all” does not work.

9. Actionable, Optimistic Path Forward (65:21)

• Accessible Longevity: Dr. Hyman stresses most people can achieve “80% of what you need” for longevity through actionable lifestyle changes, even without expensive clinics or therapies.
• Practical Tools: His book Young Forever is intentionally written to be scientifically rigorous yet extremely actionable.

Notable Quotes & Memorable Moments

• On Paradigm Shifts:
  “I don't want to manage someone's chronic disease. I want to get rid of it.” — Mark Hyman (07:00)

• On “Young Forever” Approach:
  “I'm not anti aging. I'm for healthy aging and optimal aging and for reversing our biological age… I want my physiology and my body's capacity to be kind of getting better as I get older and matching the wisdom and increased understanding of the world that happens as you get older.” — Mark Hyman (52:26, 53:55)

• On Prioritizing Interventions:
  “There’s no more powerful drug than food.” — Mark Hyman (28:44)

• On Muscle as Central to Aging:
  “You've got to maintain, keep, build muscle as you get older. It's harder to do as you get older, but you can.” — Mark Hyman (30:39)

• On the Protein Controversy:
  “If you're restricting animal protein because cancer and you're having any sugar at all, you're doing it wrong, because sugar is way stronger than animal protein at raising mtor.” — Dave Asprey (46:48)

Important Timestamps

• Hallmarks of Aging Introduction: 09:41–12:18
• Diet, Insulin, Nutrient Sensing: 18:33–22:00
• mTOR Explained (Autophagy, Fasting): 22:00–25:19
• Metformin & Lifestyle Comparison: 25:54–28:44
• Ozempic, GLP-1 Drugs & Risks: 29:59–33:05
• Rapamycin & Prospects: 33:19–39:49
• Meat vs. Plant Debate & mTOR: 41:11–47:32
• Metabolic Flexibility & Protein Recommendations: 49:26–52:26
• Inflammaging Deep Dive: 56:05–61:04
• Senescent (“Zombie”) Cells & Therapies: 61:04–62:04
• Book’s Practical Approach: 65:21–66:47

Tone and Language

The conversation is highly energetic, sometimes irreverent, science-driven but practical. Both host and guest challenge dogmas with personal anecdotes, evidence-based argument, and a willingness to “call BS” on misleading trends. Humor and storytelling are used to make the dense science relatable.

Takeaways for Listeners

• Rapid biological aging is treatable; focus on restoring health, not just disease management.
• Dietary quality and timing (especially protein) matter far more than rigid food dogmas.
• Lifestyle changes—including exercise, fasting, and sleep—are more powerful than most drugs for healthspan.
• Use advances in diagnostics but treat the root, not just markers.
• Practical, accessible steps can create real, measurable longevity benefits starting at any age; expensive interventions are “icing on the cake.”
• “Young forever” isn’t about denying age, but living with vigor, resilience, and function as the decades pass.

Further Action

• For hands-on protocols, check out Dr. Hyman’s book, Young Forever.
• Focus your own approach on foundational nutrition (favoring high-quality protein, reducing excessive carbs/sugar), exercise, sleep, and cultivating metabolic flexibility.
• Be skeptical about pharmaceutical “shortcuts” for longevity until the evidence is clear.
• Prioritize measurable, actionable health improvements over fads or one-size-fits-all advice.

This episode is a masterclass in functional-longevity thinking, and a must-listen (or must-read summary) for anyone serious about upgrading their longevity and quality of life.