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How I Biohacked the Aging Process | Dave Pascoe

Dave Pascoe is one of today’s most recognizable biohackers. The 63-year-old man takes over 170 different dietary supplements daily, experiments with anti-aging technologies like hyperbaric oxygen therapy, and attempts to prove that even “ordinary people” can significantly improve their health. According to him, his current epigenetic age is only 43, and the most flattering epigenetic age was 37.95! He currently ranks among the top 11 of the Longevity World Cup, and has previously outperformed the contest’s founder, Bryan Johnson, who spends $2M a year on anti-aging. At the 6th #TimePieLongevityForum, he shared how he has used biohacking strategies to reverse biological aging and offered practical advice for the general public.

AI Summary of Video:

Here is the high-resolution summary and analysis of the provided transcript.

A. Executive Summary

The speaker, Dave (ranked #6 on the Rejuvenation Olympics leaderboard), presents a counter-narrative to the approach popularized by billionaire Bryan Johnson (ranked #7). He argues that superior age-reversal results are achievable not through spending millions, but by mastering five physiological fundamentals: eliminating toxic exposure, consuming regenerative whole foods, constant movement for lymphatic drainage, restorative sleep for glymphatic clearance, and stress mitigation via gratitude.

While Dave admits to an aggressive “biohacking” regimen involving roughly 200 supplements and monthly blood diagnostics, he asserts that gadgets and pills are secondary to these fundamentals. A significant portion of his current protocol involves using multiple Large Language Models (LLMs)—including ChatGPT, Grok, and Gemini—to optimize his supplementation. He uses AI to resolve pharmacokinetic conflicts (e.g., mineral vs. polyphenol absorption) and to cycle compounds to alternate between mTOR activation (growth/muscle) and autophagy (cellular repair). He emphasizes that “exercise in a pill” is chemically possible but physiologically flawed because it fails to mechanically pump the lymphatic system to remove cellular waste.

B. Bullet Summary

  • Rejuvenation Olympics Ranking: The speaker outperforms billionaire Bryan Johnson on the Rejuvenation Olympics leaderboard using a protocol focused on fundamentals rather than exclusively high-cost experimental therapies.
  • The “Exercise Pill” Fallacy: Pharmaceutical mimetics for exercise are shortsighted because they cannot replicate the mechanical muscle contraction required to pump the lymphatic system and clear interstitial cellular waste.
  • Cellular Waste Dynamics: Without manual movement, cells “stew in their own waste,” blocking signaling molecules and reducing nutrient absorption efficiency.
  • Glymphatic Clearance: The brain lacks a muscular pump; it relies on deep, restorative sleep to contract and force waste through the glymphatic system.
  • Stress as a Toxin: In 2012, the speaker’s telomere length indicated a biological age of 68 at chronological age 50, attributed to chronic stress (caregiving, job loss, marathon training).
  • Mindset Reframing: Shifting internal narrative from “I have to” to “I get to” (gratitude) was a primary driver in reversing his biological age markers.
  • Dietary Protocol: Follows a “feast and famine” approach; time-restricted feeding between 12:30 PM and 5:30 PM.
  • Macronutrients: Currently high protein (to counteract muscle loss during running season), low carbohydrate, and high monounsaturated fats (olive oil, macadamia, avocado).
  • Supplement Volume: Consumes ~200 supplements daily, validated by monthly blood panels to monitor liver and kidney function.
  • Liver Support: Explicitly names Milk Thistle and TUDCA as critical agents for protecting the liver during heavy supplementation.
  • AI-Driven Optimization: Uses AI to identify antagonistic supplement pairs (e.g., minerals competing with polyphenols) and separates them into different dosing windows.
  • mTOR vs. Autophagy Cycling: utilizes an AI-designed schedule to induce mTOR (growth) for 5 days (weekdays) and autophagy (cleanup) for 2 days (weekends).
  • Cold Therapy: Prefers cold showers over immersion tubs due to hygiene and maintenance issues with home setups.
  • Therapeutic Wishlist: Identifies Plasmapheresis as a top-tier intervention he would use if cost were not a barrier.

D. Claims & Evidence Table

Claim Evidence Provided Assessment
Lymphatic flow requires muscle contraction. Anatomy citation: The lymph system has no heart/pump; relies on movement/massage. Strong. This is established physiological fact. The lymphatic system relies on the skeletal muscle pump.
Brain waste is cleared primarily during sleep. Reference to brain contraction and glymphatic system function during deep sleep. Strong. Supported by neuroscientific consensus (e.g., Iliff et al., 2012).
Stress alone aged telomeres by ~18 years. Personal telomere test results (Bio-age 68 at Chron-age 50) during a high-stress period. Speculative. While stress correlates with telomere attrition, commercially available telomere testing has high variability and other factors likely contributed.
Taking 200 supplements is safe. Personal monthly blood tests showing stable liver/kidney markers. N=1 / Risky. Polypharmacy carries significant risk of hepatotoxicity and unknown interactions. Safe for him currently, but not generally “safe.”
mTOR/Autophagy cycling improves longevity. Concept of cycling growth (weekdays) and repair (weekends) via supplements. Theoretical. The mechanism is sound based on longevity research (rapamycin studies), but the specific 5:2 supplement protocol lacks clinical trials.
Minerals block polyphenol absorption. AI analysis of chemical interactions (chelation/competition). Strong. Many minerals (iron, calcium, magnesium) are known to bind with polyphenols or compete for transporters.

E. Actionable Insights

  1. Audit Supplement Timing: Do not take all supplements at once. Use AI to separate minerals from polyphenols/catechins to prevent absorption competition (chelation).
  2. Implement the “Muscle Pump” Rule: If you work a sedentary job, mechanical movement is non-negotiable for waste removal. Chemical mimetics (like GLP-1s) do not replace the lymphatic need for contraction.
  3. Cycle Anabolism and Catabolism: Instead of constantly suppressing mTOR (for longevity) or constantly spiking it (for muscle), cycle your intake. Example: High protein/mTOR inducers on training days, fasting/autophagy inducers on rest days.
  4. Prioritize Liver Support: If taking >10 supplements daily, integrate hepatoprotective agents like TUDCA and Milk Thistle.
  5. Reframe Stressors: Apply the “I get to” vs. “I have to” cognitive reframe to active stressors. The physiological impact of gratitude is a tangible longevity lever.
  6. Hyper-Hydrate the Lymph: Lymphatic fluid requires hydration to move. Combine movement with high water intake.
  7. Optimize Sleep for Glymphatics: Prioritize deep sleep specifically, as this is the window for glymphatic clearance.

H. Technical Deep-Dive

1. The Lymphatic vs. Glymphatic Clearance Systems
The speaker correctly identifies a critical distinction in waste management.

  • Peripheral Clearance (Lymphatic): The interstitial fluid (ISF) accumulates metabolic waste. Unlike the cardiovascular system, the lymphatic system is a low-pressure, open loop system. Flow depends on extrinsic compression (skeletal muscle pump) and intrinsic rhythmic contraction of lymphangions. Sedentary behavior leads to lymphostasis, resulting in localized toxicity and inflammation.
  • Central Clearance (Glymphatic): The CNS lacks traditional lymphatic vessels. Instead, cerebrospinal fluid (CSF) enters the brain parenchyma along para-arterial spaces, mixing with ISF and washing solutes (like amyloid-beta) into para-venous spaces. Crucial Note: The interstitial space increases by ~60% during NREM sleep, drastically lowering resistance to flow. This validates the speaker’s claim that sleep deprivation inherently accelerates “brain aging” via waste accumulation.

2. Pharmacokinetic Optimization via AI
The speaker’s use of AI addresses Bioavailability Competition, a common failure point in biohacking.

  • Chelation: Polyphenols (e.g., EGCG in green tea, quercetin, curcumin) contain phenolic hydroxyl groups that bind with metal cations (Iron, Zinc, Calcium), forming insoluble complexes that are excreted rather than absorbed.
  • Transporter Competition: Amino acids and certain peptides compete for the same solute carrier (SLC) transporters in the gut lining.
  • Strategy: Segregating intake into “bio-compatible windows” (e.g., minerals AM, polyphenols PM, or separated by 2+ hours) significantly increases the effective dose (Area Under the Curve) without increasing the oral dose.

3. The mTOR/Autophagy Switch
The speaker’s 5:2 cycling addresses the “Goldilocks” problem of mTOR (Mechanistic Target of Rapamycin).

  • Chronic mTOR Activation: Leads to accelerated aging, senescence, and cancer risk.
  • Chronic mTOR Inhibition (Autophagy): Leads to sarcopenia, frailty, and immune suppression.
  • The Protocol: High protein/leucine intake (mTOR activation) during the week supports muscle synthesis (vital for the skeletal muscle pump mentioned above). Fasting or taking mimetics (e.g., Spermidine, Resveratrol, Rapamycin) on weekends triggers macroautophagy to recycle damaged organelles.

I. Fact-Check Important Claims

  • Claim: Exercise pills cannot replace movement due to lymphatic mechanics.
    • Verdict: Accurate. While drugs like SLU-PP-332 or AICAR can mimic metabolic transcription factors (increasing mitochondrial biogenesis), they do not generate the hydrostatic pressure gradients required to return lymph to the venous circulation.
  • Claim: Supplements like TUDCA regenerate the liver.
    • Verdict: Supported. Tauroursodeoxycholic acid (TUDCA) is clinically proven to reduce endoplasmic reticulum stress and prevent apoptosis in hepatocytes. It is a standard treatment for cholestatic liver diseases.
  • Claim: Telomeres of a 68-year-old at age 50.
    • Verdict: Context Required. While stress accelerates telomere shortening (Epel, PNAS, 2004), commercial telomere tests (usually measuring leukocyte telomere length) have a high margin of error and fluctuate based on immune status and inflammation. This metric should be viewed as a trend indicator rather than an absolute biological age.
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