The Human Upgrade: Biohacking for Longevity & Performance

Episode 1402: This Brain Trick Feels Like Cheating (Do THIS)
Date: January 22, 2026
Host: Dave Asprey
Guest: Dr. David Perlmutter

Episode Overview

This thought-provoking episode explores the cutting edge of brain health, neuroimmunity, and whole-body biohacking with renowned neurologist Dr. David Perlmutter. Filmed live in Las Vegas, Dave Asprey and Dr. Perlmutter dive deep into the science of microglia—the brain’s “immune cells”—their central role in neurodegenerative diseases, how metabolism governs their behavior, and actionable protocols to shift your brain’s defenders from “evil twin” to “loving and supportive.”
The discussion is rich with insights on mitochondrial health, metabolic therapies, gene therapy, psychedelics, biofield science, and the latest on GLP-1 agonist drugs (like Ozempic) for extending healthspan and influencing behavior.

Key Discussion Points & Insights

1. The Central Role of Microglia & Brain Immunity

• Microglia as the Overlords of Neuronal Health

  • Microglia, the brain's immune cells, can be friend (M2/“supportive”) or foe (M1/“evil twin”), profoundly affecting brain function.
  • Shifts from M2 to M1 are driven by metabolic dysfunction—often mitochondrial in origin.
  • [09:25] Dr. Perlmutter: “The brain's immune cells, the microglial cells, can be friend or foe ... and when they are foe, it's a consequence of their metabolism having gone awry, their mitochondrial functioning.”

• Neurodegenerative Disease as Immune-Metabolic Dysfunction

  • Alzheimer’s, Parkinson’s, and autism aren’t single-cause diseases—they are complex “recipes” involving immune dysregulation and metabolic breakdown.
  • [08:43] Dr. Perlmutter: “It’s because our brain’s immune cells have shifted to become the evil twin. And they have shifted because their mitochondria have become dysfunctional.”

• Metabolic Modulation over Symptom Suppression

  • Treating downstream symptoms (e.g., amyloid plaques in Alzheimer’s) is “treating the smoke, not the fire.”
  • The real target should be restoring healthy microglial metabolism and mitochondrial resilience.

2. Cutting-Edge Therapeutics: GLP-1 Agonists, PPAR-gamma, and Beyond

• GLP-1 Agonist Drugs & Parkinson’s “Arrest”

  • Recent trials showed GLP-1 agonists can halt Parkinson's disease progression by modifying microglial metabolism.
  • [11:29] Dr. Perlmutter: “Those individuals who were given the GLP-1 agonist drug ... Parkinson’s was totally arrested. It’s breathtaking.”

• Beyond Lifestyle—The “Big Box” of Integrative Medicine

  • Dr. Perlmutter advocates an expanded, integrative approach: combine lifestyle, pharmaceuticals, peptides, and even gene therapy, emphasizing “do no harm.”
  • [20:17] Dr. Perlmutter: “My goal is to make the box bigger and be more inclusive ... Integrate whatever works provided, above all, do no harm.”

• Microdosing Pharmaceuticals for Longevity?

  • Both agree that selective, microdosed pharmaceuticals (e.g., metformin, Actos) may help extend healthspan.
  • [21:02] Dave Asprey: “Oh, I’m all over pharmaceutical microdosing.”
  • [55:06] Dave Asprey: “Is there a role for microdosing these for healthy people?”

3. Lifestyle & Metabolic Levers for Neuroimmunity

• The “Big Levers” for Brain Health

  • Diet, sleep, exercise, social/nature connection, blood sugar/insulin control, and targeted nutrients (e.g., coQ10, urolithin A, rosmarinic acid, lithium orotate, nicotine) are primary tools.
  • [35:19] Dr. Perlmutter: “But the big levers are what you mentioned. But there are some other more exciting things ... hyperbaric oxygen, ketogenic diet, urolithin A, coenzyme Q10...”

• Biohacks for Microglial Modulation

  • Infrared/photobiomodulation, hyperbaric oxygen, 40 Hz light/sound (gamma oscillation), peptide therapies, and even gene therapy can “nudge” microglia back to their supportive role.
  • [36:02] Dr. Perlmutter: "There are ways of activating TREM2 ... the TRMM2 receptor ... People who have genetic downregulation ... have a dramatically increased risk of Alzheimer's."

4. Wider Societal and Philosophical Implications

• Diet, Inflammation & Global Behavior

  • Industrialized diets cause chronic inflammation, disconnecting populations from empathy and prefrontal cortex-driven behavior.
  • [52:33] Dr. Perlmutter: “Globally, we are keeping people away from their prefrontal cortex and locking them into ‘I am better than you.’ ... It’s happening globally as a consequence of the foods that people are eating causing more inflammation in the world.”

• GLP-1s and the Future of Behavior

  • Widespread use of GLP-1 agonists (Ozempic-like drugs) could drastically reduce gambling, shopping addictions, alcohol deaths—potentially impacting global economies.
  • [54:35] Dr. Perlmutter: “...ultimately be used in the next five years by 25% of the global population. The economic impact ... will have a multi-trillion dollar effect on global economy.”

• Oneness, Biofields, and Quantum Interconnectedness

  • The conversation explores consciousness, the human biofield, plant intelligence, quantum biology, and the science-spirituality interface.
  • [58:27] Dr. Perlmutter: “My mitochondria are talking to your mitochondria ... It’s time we recognize that.”
  • [60:28] Dave Asprey: “Everything has some level of consciousness ... you’re one with everything.”

• Kindness as the Ultimate Biohack

  • The episode ends on the importance of love, self-acceptance, and non-judgment—essential for individual and collective healing.
  • [67:10] Dr. Perlmutter: “Love thy neighbor as thyself ... It’s not conditional ... and it’s hard to do.”
  • [68:27] Dave Asprey: “Judgment is an egoic manifestation. It’s your mitochondria trying to be safe.”

Memorable Quotes & Moments

• On Treating the Root, Not the Symptom

  • Dr. Perlmutter [09:39]: “By the time we get to targeting beta amyloid with these drugs, we’ve missed a lot of opportunities. Let's go upstream and ask, why did the amyloid accumulate?”

• On Bold, Integrated Medicine

  • Dr. Perlmutter [20:17]: “No, the goal is to make the box bigger ... It's the difference between alternative medicine and integrative medicine.”

• On Consciousness & Mitochondria

  • Dave Asprey [42:31]: “I think the ego is actually a manifestation of mitochondria...”

• On Microdosing Longevity Drugs

  • Dave Asprey [21:02]: “Oh, I'm all over pharmaceutical microdosing.”
  • Dr. Perlmutter [55:06]: “It's a great question. I'd love to see people study it.”

• On the Need for Kindness

  • Dr. Perlmutter [67:10]: “Love thy neighbor as thyself. ... And then part two is as thyself. And that might even be harder.”

Notable Timestamps and Segments

• 03:18 – Introducing Dr. David Perlmutter (bio, accolades, heart)
• 04:18–08:43 – Autism, Alzheimer’s, spectrum disorders as “recipes,” not single-cause diseases; dangers of reductionism in medicine.
• 09:25–11:45 – Microglial "friend or foe," mitochondria as root of immune dysfunction in brain, GLP-1 Parkinson's clinical trial result.
• 13:16–13:50 – The reversibility of microglial state (M1/M2); metabolic nudges.
• 16:26–19:23 – Glial cells as “overlords,” microglia in brain and immune modulation; PPAR gamma and drug-induced polarization.
• 21:01–25:13 – Open discussion on gene therapy, mold, glyphosate, and environmental toxicity’s impact on brain health.
• 28:12–30:59 – Personal stories: raising pigs, the psychology of food and ancestral eating.
• 32:59–41:05 – Parkinson’s origin from synthetic heroin, how immune activation persists; mitochondrial sharing between cells.
• 42:31–46:21 – The ego, mood, and mitochondrial function; feedback loops of inflammation, mood, and behavior.
• 52:33–54:50 – The "global amygdala takeover" via processed foods; GLP-1s reducing addictive behavior.
• 58:24–63:19 – Quantum entanglement, collective consciousness, the informational field, Darwin, sunflowers, and the definition of life.
• 67:10–69:34 – The primacy of kindness, loving oneself and others, the futility of external validation.
• 69:47–70:40 – Longevity, healthspan, happiness, and love as ultimate goals.
• 74:10–75:50 – Heart-brain connection, biofield, entropy, spirit energy, universal goodness.

Tone and Style

The conversation is both deeply scientific and openly philosophical, blending biochemistry, clinical anecdotes, cutting-edge research, and sweeping existential thoughts—punctuated by both speakers’ dry humor and warmth.

Useful for Listeners Who Haven’t Tuned In

• Understand the current scientific view that chronic disease, brain health, and behavior are fundamentally metabolic and immune issues.
• Get next-level insights on therapies that move the needle: drugs (GLP-1 agonists, metformin, peptides), red and infrared light, lifestyle, and even consciousness practices.
• Hear why empathy, kindness, and non-judgment—as practiced and articulated by highly credentialed experts—are not just spiritual ideas, but crucial for personal and societal healing.
• Gain actionable recommendations (diet, sleep, fasting, photobiomodulation, select supplements/pharma, mind-body modalities) to protect and repair your brain’s “defenders.”
• Be inspired to integrate rigorous science with compassion, open-mindedness, and a holistic worldview in your own health journey.

Final Takeaway

“Let’s take those neurons down a couple notches and elevate the microglia as equally valuable. The day of the microglia.”
— Dr. David Perlmutter [76:06]

“All of this—the idea of biohacking itself—is a Trojan horse to get people to pay attention to longevity and consciousness.”
— Dave Asprey [69:47]

For more brain hacks, practical protocols, and conversations that weave together hard science and human kindness, tune in weekly to The Human Upgrade with Dave Asprey.