As requested
1. Tidied, lightly‑edited transcript
(Filler words, repetitions and time‑stamps removed; sense preserved but phrasing occasionally tightened for readability.)
Intro – “Three Hot Longevity Papers”
Welcome to the Optispan podcast. Today I’ll discuss three recent papers that have been buzzing around the longevity world—two concerning rapamycin (my “vitamin R”) and one on taurine.
Paper 1 – Rapamycin for Alzheimer’s disease (AD)
The study (“Rapamycin treatment for Alzheimer’s disease and related dementias: a pilot phase‑1 clinical trial”) enrolled ten people aged 55–85 with mild cognitive impairment or mild AD.
- Design: open‑label, no placebo, 1 mg rapamycin /day for eight weeks.
- Primary aim: detect rapamycin in cerebrospinal fluid (CSF). Secondary aims: safety, cognition, CSF/plasma inflammatory markers.
Why 1 mg/day? No rationale is given. Transplant patients take several mg/day; longevity self‑experimenters favor 4–10 mg once weekly to achieve high peaks then troughs below detection, which seems both safer and more effective.
Blood data from the same group’s earlier work show 1 mg/day only yields 4–8 ng/ml in serum. Even if 10 % crossed into CSF, that would be 0.4‑0.8 ng/ml—below the assay’s 1 ng/ml limit. Unsurprisingly, the study found no CSF rapamycin. An ALS trial that used ~2–4 mg/day likewise found none.
Side‑effects were minimal, but without a placebo we can’t know if rapamycin mattered. Three CSF biomarkers (p‑tau, GFAP, NfL) rose slightly yet significantly—but the between‑person variance dwarfed the change, and natural disease progression wasn’t controlled. The authors themselves state the outcomes “cannot be clearly interpreted.”
A better‑designed phase‑2a trial (“RAP‑AD”) will dose 7 mg weekly and include imaging, cognition and CSF levels; that should be far more informative. Importantly, rapamycin might not need to enter the brain directly; systemic mTOR inhibition could indirectly suppress brain mTOR activity.
Early human data in APOE‑ε4 carriers already hint at improved brain volume and perfusion with rapamycin.
Paper 2 – Rapamycin for chronic fatigue syndrome (CFS / ME‑CFS)
A new pre‑print (“Low‑dose rapamycin alleviates clinical symptoms of fatigue and post‑exertional malaise via improved autophagy”) followed 86 ME‑CFS patients in a decentralized, uncontrolled study.
- Dose: 6 mg once weekly for 90 days (after a short ramp‑up).
- Completed: 40 participants (high drop‑out, partly because they paid out of pocket).
- Outcomes: validated self‑report tools (BAS, SSS, MFI‑20, SF‑36) and blood markers of autophagy (Beclin‑1 ↑, pS258‑ATG13 ↓).
Results: 29/40 (~73 %) reported strong improvement in fatigue, post‑exertional malaise and orthostatic intolerance, with p‑values < 1 × 10⁻⁴. Post‑infectious cases (e.g., long‑COVID) improved the most. Lab chemistry showed no changes in HbA1c, fasting glucose or lipids, and adverse events were mild and transient.
Limitations: no placebo, self‑report, heterogeneous pharmacy formulations, three‑month duration. Yet molecular changes line up with symptom gains, suggesting a real effect. Author’s takeaway: if you have moderate–severe ME‑CFS, weekly rapamycin is worth discussing with your physician.
Paper 3 – “Is taurine an aging biomarker?”
A Science paper reassessed whether circulating taurine declines with age. Using longitudinal cohorts of humans, monkeys and mice, the authors found no consistent age‑related drop, challenging the 2023 report that had spurred taurine‑supplement enthusiasm.
The new work does not test taurine supplementation’s ability to extend lifespan or healthspan, so it tells us nothing about taurine as an intervention. The press‑release comment that taurine’s efficacy “may be context‑dependent” is a truism: everything in biology is context‑dependent. Without the hard replication of the lifespan data, this feels like an expensive non‑answer.
Outro
Of today’s three papers, two (rapamycin‑AD and taurine) were disappointing; the ME‑CFS study, despite caveats, looks genuinely promising. Questions welcome—let me know where I’m wrong.
2. Executive summary
| Study |
What was done |
Key findings |
Host’s verdict |
| Rapamycin 1 mg/day in AD |
n = 10, open‑label, 8 weeks; looked for CSF drug & biomarkers |
No CSF rapamycin; small biomarker shifts of uncertain meaning |
“Very unimportant”— dose too low, duration too short, no placebo |
| Rapamycin 6 mg weekly in ME‑CFS |
n = 86 (40 completers), decentralized, 3 months |
~73 % reported marked clinical improvement; supportive autophagy markers; minimal side‑effects |
Potentially game‑changing for post‑infectious ME‑CFS; deserves larger RCT |
| Taurine biomarker study |
Longitudinal measurement in humans, monkeys, mice |
Taurine levels do not reliably fall with age |
Technically solid but addresses a low‑value question; says nothing about supplementation benefits |
3. Critique
3.1 Rapamycin–Alzheimer’s pilot
The host’s skepticism is warranted. A phase‑1 pilot can sacrifice statistical power for safety data, but dose and endpoint must still be justifiable. Here:
-
Dose mismatch – 1 mg/day was almost guaranteed to stay below CSF detection. The investigators even omitted serum rapamycin levels, so we cannot correlate exposure with biomarker changes.
-
No control arm – in progressive AD, eight weeks without placebo cannot distinguish treatment effect from natural variability.
-
Over‑interpretation on social media – calling it a “VERY IMPORTANT study” (per the viral tweet) misrepresents the findings. The host pushes back appropriately.
However, the study is not entirely useless: it re‑confirms safety at low daily dosing in cognitively impaired elders and sets the stage (via IRB groundwork) for the higher‑dose weekly RAP‑AD trial now underway. (ResearchGate, Scholars @ UT Health San Antonio)
3.2 Rapamycin–ME‑CFS pre‑print
Strengths the host notes—and I agree—include:
- Consistent, large effect sizes across multiple validated scales.
-
Biological coherence – ATG13 phosphorylation dropping fits the proposed mTOR–autophagy mechanism.
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Real‑world setting – multiple clinics, heterogeneous formulations resemble day‑to‑day practice.
But some caveats deserve sharper emphasis:
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Attrition bias – losing >50 % of participants risks inflating perceived efficacy if non‑responders preferentially quit.
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Placebo effect – fatigue and PEM are highly placebo‑responsive; subjective scores without blinded controls can overestimate benefit.
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Short follow‑up – three months may miss late adverse events or waning efficacy.
Still, given the dire therapeutic vacuum in ME‑CFS, even an imperfect open‑label signal is valuable and justifies a rapid, well‑powered RCT. (PubMed , ResearchGate)
3.3 Taurine biomarker study
Here the host may undervalue negative results. Demonstrating no longitudinal decline undermines the narrative that falling taurine drives aging; that matters if taurine’s advocates invoke deficiency as rationale. Yet I share the criticism that the study stops short: lifespan or functional read‑outs in mice (easy and inexpensive by comparison) would have answered the pressing question of intervention efficacy. The opportunity cost—allocating primate resources to descriptive plasma work rather than a replication of the 2023 supplementation experiment—feels high. (Science, National Institutes of Health (NIH), PubMed )
Bottom line
-
AD pilot: Tells us little; higher‑dose weekly trials are the real test.
-
ME‑CFS pre‑print: Early but encouraging; warrants controlled follow‑up.
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Taurine biomarker: Elegant rebuttal of a minor claim, but leaves the core intervention question unanswered.
For clinicians and patients: weekly rapamycin remains investigational but is showing a favorable safety‑signal and potential in post‑viral fatigue; taurine’s longevity benefits remain speculative until supplementation outcomes are replicated.
