#1

New study in preprint.

Longevity expert Dr. Matt Kaeberlein breaks down three new scientific studies on the popular anti-aging drug rapamycin and the supplement taurine. Discover which research shows real promise for conditions like chronic fatigue and which studies are being overhyped in the longevity community. 0:00 - Intro: 3 Hot Longevity Papers 0:29 - Rapamycin for Alzheimer’s: A Flawed Study? 17:53 - A Breakthrough for Chronic Fatigue? (New Rapamycin Study) 23:29 - The Promising Results: How Rapamycin Helped 34:44 - Taurine: Does It Really Affect Aging? 39:20 - The Big Miss: What the Taurine Study Didn’t Do 41:13 - Final Take: What This Science Actually Means for You

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#2

This is a really great video by MK, well worth watching. I was particularly interested in his remarks on rapa and crossing of the BBB.

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#3

From chatGPT o3.

Tidied-Up Transcript

(Filler words, digressions and repeated phrases removed; technical terms standardised; approximate time-stamps retained for navigation)

Intro – “Three Hot Longevity Papers” (0 min)

Host: “Welcome to the Optispan podcast. Today we’ll look at three recent papers that have been buzzing around the longevity community—two on everyone’s favourite molecule, rapamycin, and one on the amino-acid derivative taurine.”

Paper 1 – Rapamycin for Alzheimer’s disease (0 : 29 – 17 : 46)

Tópico Key Points
Study referenced Rapamycin treatment for Alzheimer’s disease and related dementias: a pilot phase-1 trial – 10 patients with mild cognitive impairment or mild AD; open-label; 1 mg/day for 8 weeks.
Author’s Twitter storm Alex Zhavoronkov called it a “VERY IMPORTANT study.” Host felt the tweet oversold the paper.
Design flaws (as argued by host) • No placebo arm • Dose too low (1 mg/day) and too short (8 weeks) to reach CNS or show clinical change • CSF rapamycin was undetectable—exactly what PK calculations predict.
Why detection was unlikely Peak blood levels at 1 mg/day are ≈4–8 ng/mL; CSF is typically ≤10 % of plasma, below assay sensitivity. Earlier ALS work at higher doses also showed no CSF penetration.
Secondary read-outs Small, statistically significant increases in p-tau-181, GFAP and NFL, but effect sizes dwarfed by baseline variability; impossible to interpret without controls.
Take-home Study is not “very important”; tells us little about efficacy. A better-designed phase-2a trial (the RAP study) is already under way using 7 mg weekly with CSF, PET and MRI outcomes.

Paper 2 – Rapamycin for ME/CFS (17 : 53 – 34 : 44)

Tópico Key Points
Pre-print Low-dose rapamycin alleviates fatigue and PEM in chronic-fatigue-syndrome patients via improved autophagy – 86 enrolled, 40 completed; decentralised, uncontrolled.
Dosing Titrated to 6 mg once weekly for 90 days (standard “longevity” regimen).
Outcome measures Bell Activity Scale, Symptom Severity Score, Multidimensional Fatigue Inventory, SF-36, plus plasma Beclin-1 and p-ATG13.
Results • 29/40 (≈75 %) were “strong responders” with large improvements in fatigue, PEM and quality-of-life metrics (p < 10⁻⁵). • Molecular markers changed in the predicted direction (↓p-ATG13, ↑Beclin-1). • No significant adverse events; HbA1c, fasting glucose, TGs, LDL and HDL unchanged.
Limitations No placebo; high attrition; heterogeneous pharmacy sources; patient-reported outcomes susceptible to placebo effect.
Author’s verdict Signal looks real and clinically meaningful, especially in post-viral CFS. Encourages physicians and patients to consider supervised off-label use while awaiting RCTs.

Paper 3 – “Is Taurine an Aging Biomarker?” (34 : 44 – 41 : 08)

Tópico Key Points
New Science paper Longitudinal human, monkey and mouse data show no consistent age-related fall in circulating taurine.
Contrast with 2023 study Earlier paper (in which the host was a minor co-author) reported age-dependent decline and lifespan extension from taurine supplementation in model organisms.
Host’s critique • New work convincingly questions taurine as a biomarker, but sheds no light on whether supplementation slows ageing. • Would have been more useful (and worthy of Science) to replicate/ refute the lifespan data.
Practical takeaway Host neither takes nor recommends taurine; nothing in the new paper changes that stance.

Conclusion (41 : 13 – 42 : 43)

  • Two papers (rapamycin–AD pilot; taurine biomarker study) are “disappointing” or over-interpreted.
  • One paper (rapamycin–ME/CFS) looks promising despite limitations; supports the wider safety-and-efficacy picture for weekly rapamycin.
  • Viewers invited to challenge the analysis and ask follow-up questions.

Video Summary (in ≤ 200 words)

In this episode of the Optispan podcast, longevity scientist Matt Kaeberlein dissects three recent papers.

  1. Rapamycin for Alzheimer’s disease: A ten-person, open-label phase-1 trial used just 1 mg/day for eight weeks and failed to detect rapamycin in CSF or show credible biomarker improvement. Kaeberlein argues the dose and design guaranteed a null result and criticises social-media hype around the study.
  2. Rapamycin for chronic-fatigue syndrome: A decentralised pre-print following 40 ME/CFS patients on 6 mg once-weekly rapamycin for three months reports marked improvements in fatigue, post-exertional malaise and quality-of-life scores, with supportive autophagy biomarkers and minimal side-effects. He calls the signal compelling and clinically actionable, pending larger RCTs.
  3. Taurine as an ageing biomarker: A new Science paper finds no universal decline of taurine with age in humans or animal models, challenging part of a 2023 study. While methodologically solid, it leaves the key question—does taurine supplementation extend lifespan?—unanswered.

Kaeberlein’s overall verdict: ignore the Alzheimer’s pilot, stay sceptical but curious about taurine, and pay serious attention to rapamycin’s potential in post-viral fatigue conditions.

Critique of the Video

Aspect Strengths Weaknesses / Caveats
Scientific reasoning Carefully explains pharmacokinetics (e.g., why 1 mg/day rapamycin cannot reach detectable CSF levels). Provides mechanistic links (mTOR → autophagy → fatigue). Occasionally ventures into opinion (“useless study”, “big nothing-burger”) that may feel dismissive rather than analytical.
Use of evidence Cross-references earlier PK data and ALS trial; cites pending RAP phase-2a protocol. Summarises strong statistics in ME/CFS study. Relies heavily on author’s own calculations and anecdotal community data without displaying raw numbers from papers; viewers must trust his interpretation.
Balance & fairness Admits when his own tweet was “too reactionary” and apologises to authors. Acknowledges limitations (no placebo, attrition) of the CFS study even while optimistic. Taurine section downplays value of falsifying a biomarker hypothesis; could have acknowledged that rigorous negative findings prevent mis-allocation of resources.
Communication Jargon translated into plain language; clear segmentation; invites audience feedback. Video runs >40 minutes; pacing slowed by repeated explanations.
Impact & originality Highlights under-reported ME/CFS data and situates within broader mTOR literature—useful for clinicians. Alzheimer’s and taurine critiques echo points already circulating in geroscience blogs; novelty lies more in synthesis than in new insights.

Bottom line: The episode is a solid, mostly evidence-based tour through three topical studies. Viewers get a crash course in rapamycin dosing logic and an intriguing, if preliminary, look at its promise for ME/CFS. The critical tone is refreshing but occasionally slips into rhetoric; a bit more quantitative detail and acknowledgement of counter-arguments would strengthen the analysis.

References
• Phase-1 rapamycin-AD trial details – PubMed (pubmed.ncbi.nlm.nih.gov)
• ME/CFS rapamycin pre-print summary – PubMed (pubmed.ncbi.nlm.nih.gov)
• Taurine biomarker study – PubMed / NIH News Release (pubmed.ncbi.nlm.nih.gov, nih.gov)

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