I’m subscribed to a number of longevity newsletters and I just received this email.
Rapid progress has been made in our OSK (Yamanaka factor) primate rejuvenation study.
The first group of monkeys will be injected with an OSK-RNA construct within a matter of days.
We demonstrated efficacy of this OSK construct in live mice with robust transfection results in multiple organs.
To view my 32-minute November 2025 presentation about OSK systemic regeneration and living longer, click below:
Monkey Project is Fully Funded
This multi-million dollar primate study is being paid for with proceeds from blood tests and supplements you purchase from Life Extension®.
It is fully funded and does not require donations. I will continue funding it as long as the treated monkeys remain healthy and alive with no upper limit age threshold.
Video Summary: Longevity, OSK Gene Therapy, and Aggressive Lipid Management
A. Executive Summary
The speaker presents a bifurcated strategy for radical life extension: immediate lifestyle/pharmaceutical intervention and near-future genetic reprogramming. The presentation highlights the lethality of sedentary behavior, asserting that ultra-processed foods and lack of movement significantly increase mortality risk. The core scientific announcement concerns Yamanaka Transcription Factors (OSK). The speaker reveals unpublished internal data (dated November 2025) claiming successful systemic transfection of OSK into the heart and liver of mice using **Lipid Nanoparticles (LNPs)**carrying mRNA. This method reportedly outperforms plasmid DNA vectors in sustainability and biodistribution. Consequently, the group announces the immediate commencement of primate trials (African Green Monkeys) in December 2025.
Parallel to this, the speaker advocates for aggressive cardiovascular risk management, referencing Dr. Peter Attia. They argue that standard reference ranges for Apolipoprotein B (ApoB) and C-Reactive Protein (CRP) are dangerously permissive. The central thesis is that “normal” is pathologically high; to survive long enough for gene therapies, individuals must use pharmacological tools (statins, PCSK9 inhibitors) to drive ApoB levels down to the 30–40 mg/dL range.
B. Bullet Summary
Sedentary Lethality: A 2024 study suggests sedentary individuals have a 300% higher risk of sudden death compared to active counterparts.
Minimum Effective Dose: Walking just 15 minutes daily can significantly mitigate mortality risks; high-intensity interval training (HIIT) offers superior benefits.
Exponential Tech: The speaker uses the timeline of communication technology (Paper to iPhone) to argue that age-reversal tech will scale exponentially once the “code” is cracked.
Yamanaka Factors (OSK): The group utilizes Oct4, Sox2, and Klf4 (OSK), excluding c-Myc to avoid oncogenic (cancer) risks.
Delivery Mechanism Victory: Internal trials compared Viral Vectors, Polymers/Plasmids, and Lipid Nanoparticles (LNPs). LNPs with mRNA showed the most robust, sustainable expression.
Transfection Success: Preliminary November 2025 data shows successful OSK transfection in mouse heart and liver tissues after a single injection.
Primate Trials: Efficacy and safety trials on African Green Monkeys are scheduled for December 9–12, 2025, to test age reversal via LNP/mRNA.
Future Delivery: The goal is a monthly syringe of mRNA OSK delivered to patients to induce partial cellular reprogramming.
Cardiovascular Markers:ApoB (Apolipoprotein B) and CRP (C-Reactive Protein) are cited as the critical biomarkers for heart disease.
Flawed Standards: Standard medical reference ranges (ApoB < 100 mg/dL) are criticized as normalizing disease states.
Target Levels: The speaker advocates for ApoB levels between 30–40 mg/dL (referencing Peter Attia) and non-detectable CRP.
Pharmacology Required: Achieving these low levels usually requires aggressive pharmacotherapy (Statins, PCSK9 inhibitors like Repatha/Leqvio, Ezetimibe).
Personal Data: The speaker (age 71) claims an ApoB level of 24 mg/dL through strict intervention.
The “Gap” Strategy: The primary goal of current lipid management is to survive the “gap” years until OSK gene therapies become clinically available (projected potential human trials in 2026).
D. Claims & Evidence Table
Claim
Evidence Provided
Assessment
Sedentary lifestyle increases sudden death risk by 300%.
Cites “huge study published at the end of 2024” (specific citation not named in text).
Plausible. High relative risk correlates with severe inactivity, though “300%” likely compares extremes (bedbound vs. active).
OSK (Oct4, Sox2, Klf4) reverses aging without cancer.
Strong Pre-clinical. Validated in mice models (e.g., David Sinclair’s lab, Salk). Human translation remains Speculative.
LNP/mRNA is superior to Plasmid DNA for OSK delivery.
Internal unpublished data (Nov 2025) showing sustained expression (21+ days) vs. rapid drop-off for plasmids.
Promising but Verification Needed. Unpublished internal data cannot be independently verified yet, but aligns with broader mRNA biotech trends.
ApoB is a better predictor of CVD than LDL-C.
References Dr. Peter Attia (“Outlive”) and general lipidology consensus.
Strong. Widely accepted in advanced lipidology; ApoB captures total particle burden.
Ideal ApoB target is 30–40 mg/dL.
Clinical anecdotal evidence from aggressive preventative medicine (Attia); references risk curves.
Aggressive/Debated. Mainstream guidelines suggest <70 or <55 for high risk. <40 is “physiological for a neonate” but controversial for general pop.
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E. Actionable Insights
Execute the “15-Minute Rule”: If you are sedentary, immediate integration of 15 minutes of continuous walking daily is the minimum viable intervention to reduce immediate mortality risk.
Order Specific Blood Panels: Do not rely on a standard lipid panel. Explicitly request ApoB and hs-CRP (High-sensitivity C-Reactive Protein) tests.
Target Aggressive Lipid Suppression: Ignore “Normal” (<100 mg/dL) on lab reports. Aim for ApoB < 60 mg/dL. If you are high-risk or a longevity enthusiast, consider discussing pharmacological suppression to < 40 mg/dL with a preventive cardiologist.
Evaluate Lipid Lowering Drugs: Investigate PCSK9 inhibitors (e.g., Repatha, Leqvio) or combination therapy (Statin + Ezetimibe) if lifestyle alone does not crush ApoB levels.
Monitor OSK Gene Therapy: Follow the specific progress of mRNA via Lipid Nanoparticles. This is the likely modality for the first generation of human age-reversal treatments.
Incorporate HIIT: Move beyond walking to High-Intensity Interval Training to maximize mitochondrial efficiency and VO2 max.
H. Technical Deep-Dive: OSK & Partial Reprogramming
The transcript discusses Partial Cellular Reprogramming, a technique derived from the discovery of Yamanaka Factors (Nobel Prize, 2012).
The Factors: The original cocktail is OSKM (Oct4, Sox2, Klf4, c-Myc).
The Modification: The speaker emphasizes the use of OSK, deliberately excluding c-Myc. c-Myc is a potent oncogene; while it accelerates reprogramming, it significantly increases the risk of teratomas and malignant tumors. The industry consensus (followed here) is that OSK offers a safer therapeutic window for rejuvenation without dedifferentiating cells to a cancerous state.
Mechanism of Action: These transcription factors bind to DNA and reset the epigenetic clock (DNA methylation patterns), effectively reversing the cell’s biological age while maintaining its identity (e.g., a liver cell becomes a younger liver cell, not a stem cell).
The Vector Battle:
Viral Vectors (AAV): Efficient but carry risks of immunogenicity and insertional mutagenesis.
Plasmids (pDNA): Safer but demonstrated poor transfection efficiency and short duration in the speaker’s data (expression lost after ~3 days).
mRNA via Lipid Nanoparticles (LNP): The winning modality in their tests. LNPs protect the mRNA payload and facilitate endosomal escape. The data indicates this method achieved systemic transfection (heart/liver) and sustained expression (up to 21 days), likely due to the stability of the LNP formulation and the efficiency of the ribosomal translation of the mRNA blueprint.
I. Fact-Check: Cardiovascular Claims
Claim:Standard ApoB reference ranges (up to 100 mg/dL) are too high; 30-40 mg/dL is the target.
Consensus View: The American College of Cardiology (ACC) and AHA guidelines generally target LDL-C < 70 mg/dL (roughly ApoB < 80 mg/dL) for those with established cardiovascular disease.
Longevity/Aggressive View: The speaker aligns with Dr. Peter Attia and Dr. Allan Sniderman, who argue that atherosclerosis is driven by the number of atherogenic particles (ApoB).
Evidence: Neonates typically have ApoB levels of ~20-30 mg/dL and show no atherosclerosis. Hunter-gatherer populations often maintain levels far below Western norms (approx 50-70 mg/dL) with minimal heart disease.
Verdict: The claim is Medically Accurate within the context of optimal longevity and atherosclerosis prevention, though it is far more aggressive than the “Standard of Care” which balances cost/benefit for the general population.
