The mice in the ITP study also appeared to have metabolic disfunction yet they lived longer, part of the answer is in the following study
And don’t know how many people got rapamycin in the Stanfield study but by now there are many of us here, taking it for many years now and I don’t think anyone of us got any serious side effects definitely attributed to rapamycin
The ITP paper does not explicitly discuss or provide data to demonstrate whether rapamycin increases or improves specific metabolic dysfunctions. Could you please share your data source?
Moreover, even if both humans and mice(ITP) exhibit metabolic dysfunction, does that prove that this can be used to extend human lifespan?
Never mind. I had a feeling I might get a lot of criticism, so I deleted my original comment. I’ve watched all his interview videos, and there are quite a lot of outrageous things.
I think you are talking about “clinical trials” that use certain biological or epigenetic clocks, which we know are not ready for prime time and that do not measure all aspects of aging.
I hear you but need a small correction. I think you might need to use past tense when you refer to him. I doubt he “IS” any longer because he’s been dead for over a year now LOL, other than that I do get your point
The provided analysis of the 13-week human trial is heavily skewed toward a binary “pass/fail” interpretation of gerotherapeutics. While the raw data accurately reflects the outcomes of that specific trial, the conclusions drawn from it contain significant mechanistic blind spots and biological misconceptions.
Here are the primary flaws in the analysis, cross-referenced with the 2026 Hibbert et al. Science Advances data and broader pharmacological literature.
1. The Hypertrophy Fallacy: Conflating “Power” with “Adaptation”
The analysis concludes that rapamycin “blunts muscular strength adaptations” and provides “zero measurable physiological or functional benefits” because of lower repetitions in the 30-Second Chair-Stand Test. This is a profound misinterpretation of muscle biology.
The Flaw: The chair-stand test primarily measures explosive concentric power, which is directly dictated by the cross-sectional area (thickness) of muscle fibers. The Hibbert et al. (2026) [cite_start]study definitively proves that this specific type of growth—radial growth—is mediated entirely by the rapamycin-sensitive mTORC1 pathway[cite: 13, 167]. By administering a 6 mg weekly dose, the trial successfully inhibited mTORC1, thereby predictably blunting radial hypertrophy and the resulting concentric power generation.
The Ignored Benefit: The analysis completely ignores the existence of longitudinal growth. [cite_start]Hibbert et al. demonstrated that mechanical loading induces the in-series addition of new sarcomeres (lengthening the muscle fiber) via a completely rapamycin-insensitive mechanism[cite: 13, 172, 703]. [cite_start]Claiming there are “zero physiological benefits” ignores that these subjects were likely still undergoing profound structural remodeling, increasing fascicle length and altering contraction velocity, even while their radial “power” adaptations were chemically locked[cite: 706, 770].
2. Mischaracterization of the “Starvation Phenotype” as Toxicity
The analysis points to elevated HbA1c (+1.74 mmol/mol) and LDL cholesterol (+0.32 mmol/L) as “objective proof” of “measurable degradation” and metabolic dysfunction.
The Flaw: In the context of mTOR inhibition, these lipid and glucose shifts are not necessarily indicative of pathological toxicity; they are well-documented features of a state often called “pseudo-diabetes” or the “starvation phenotype.”
When mTORC1 is inhibited, the body mimics a state of nutrient scarcity. It suppresses lipid storage (resulting in a transient rise in circulating LDL as lipids remain in the blood) and initiates peripheral insulin resistance to spare circulating glucose for the brain (slightly elevating HbA1c). Equating an adaptive survival phenotype to pathological metabolic disease is a common error in translating standard clinical biomarkers to longevity interventions.
3. The Epigenetic Time-Horizon Fallacy
The author asserts there is “zero quantitative evidence” of anti-aging benefits because epigenetic clocks (GrimAge, etc.) showed negligible differences over the 13 weeks.
The Flaw: Epigenetic clocks track the long-term, cumulative methylation changes of cellular aging. Expecting a 13-week (91-day) protocol to yield statistically significant, systemic reversals in human DNA methylation is biologically naive. The absence of epigenetic age reversal in a single financial quarter is a limitation of the study’s duration, not definitive proof of the drug’s inefficacy as a geroprotector.
The analysis states that mean C-Reactive Protein (CRP) increased by 4.26 mg/L, framing this as a failure of rapamycin’s anti-inflammatory properties, while simultaneously admitting the data was skewed by two massive outliers (17 mg/L and 50 mg/L).
The Flaw: A CRP of 50 mg/L indicates an acute phase response—typically a severe bacterial infection (which perfectly aligns with the single reported Serious Adverse Event of community-acquired pneumonia). Allowing acute infection outliers to dictate the mathematical mean, and then using that skewed mean to declare the drug lacks basal systemic anti-inflammatory properties, represents poor data interpretation.
5. Protocol Failure vs. Mechanism Failure
The overarching conclusion strips away “theoretical optimism” to declare a “definitive negative result” for the drug.
The Flaw: The trial does not prove that rapamycin is a failure; it proves that this specific protocol (combining an exercise intervention with a high-trough 6 mg weekly dose) creates a biological conflict of interest. You cannot maximally stimulate radial muscle hypertrophy (which requires mTORC1) while simultaneously dosing a compound designed to block it. The blunted functional gains are a failure of timing and pharmacokinetics, not a failure of the molecule’s longevity potential.
It’s hard to even know what to make of this AI-on-AI analysis. The study only looked at short-term data, and every conclusion is strictly qualified by that 13-week window. If I ran your critique through an AI again, it would just hallucinate even more errors.
You stated this in your analysis. Are you now saying you don’t agree with your post? Why post it if you don’t agree with it?
Your posting / analysis seems to largely be a “straw man” analysis. It was a short-term muscle study, it tell us nothing about the long-known benefits of longevity that rapamycin has demonstrated in dozens and dozens of studies.
The original commentary explicitly limited its conclusions to a 13-week or short-term timeframe, as that is what the raw data reflects.
I simply used Gemini Pro to analyze the data from this specific paper, using prompts strictly designed for objective analysis. Therefore, any conclusions are limited to the scope of this study alone. I am confident that the AI followed my instructions and did not extrapolate findings beyond the actual timeframe of the trial.
Exactly. The analysis was strictly limited to the data in that paper, and I certainly didn’t bias the prompts to favor any specific outcome. Gemini Pro’s use of ‘anti-aging’ was merely a description of the epigenetic clock, and ‘anti-inflammatory’ referred specifically to the C-Reactive Protein levels. If those terms are problematic, I’m happy to remove them and leave only the raw data. Since those descriptions seem to have touched a nerve, I’ll ensure the AI strips away any descriptive labels for the metrics next time.
Gemini Pro:
Approximately 0.81% of the total U.S. population is male and 85 or older. This accounts for roughly 2.8 million male individuals.
Well, I am finally in a group of less than 1%; though rare, you see us everywhere. Apparently a high dose of rapamycin for five years isn’t killing me.
Yeah, I’m familiar with this paper. Alan Green mentioned in an interview that Matt Kaeberlein personally flew from Washington to New York to get an email list from him of 900 patients taking rapamycin for anti-aging. Professor Kaeberlein sent out surveys to all of them and got over 300 replies from rapamycin users, which formed the basis of this study. I bet a lot of people on this forum actually filled out that questionnaire. To be honest, I haven’t read the paper that closely. For me, the most important takeaway is that 90% of people using rapamycin for anti-aging are on a 6mg dose.
Haha, actually I’m more curious about how many dollars Matt Kaeberlein paid those patients as a thank you for filling out the questionnaire. The response rate was quite high; if they didn’t receive any compensation, then those patients were truly selfless.
Given that this paper is so important and represents the hard work of biohackers, posting comments indeed requires very careful and repeated consideration. However, I noticed that no one seems to have uploaded the PDF version of this paper. Although it claims to be free, downloading it without an institutional account incurs a fee. Therefore, I’ll take the opportunity to upload the PDF version without offering any interpretation.
After some thought, perhaps no one uploaded it because of commercial copyright concerns. Making the PDF publicly available might not be appropriate. After further consideration, I decided to delete it. It seems that only sharing it via private messages would be legal.
Muscle tightness: Users 29.8% vs. Non-users 45.3%.
Depression: Users 4.1% vs. Non-users 15.1%.
Anxiety: Users 7.3% vs. Non-users 18.0%.
Eye pain: Users 3.7% vs. Non-users 11.6%.
Specific Infection Data Not Reaching Statistical Significance:
Respiratory tract infection: Users 14.7% vs. Non-users 8.1%.
Skin infection: Users 6.1% vs. Non-users 2.3%.
Urinary tract infection: Users 2.9% vs. Non-users 1.2%.
V. Self-Reported COVID-19 Infection Data
Overall Infection Rate: The user group reported an infection rate of 28.5% (95 cases), while the non-user group reported 31.3% (54 cases).
Disease Severity (Classified by Usage Group):
Continuous user group (n=37): Took rapamycin before, during, and after infection. Mild 88.5%, Moderate 13.5%, Severe 0%, Long-COVID symptoms 0%.
Non-user group (n=54): Mild 50.0%, Moderate 46.3%, Severe 3.7%, Long-COVID symptoms 5.6% (3 cases).
Statistical Results: Continuous rapamycin users were significantly less likely to have experienced a moderate or severe infection compared to non-users (p < 0.005).
VI. Subjective Self-Evaluation Questionnaire Results
In the subjective agreement survey regarding rapamycin user experiences, the top three indicators were:
“My health has improved since taking rapamycin”: 44.7% Agree, 5.7% Disagree.
Wow, that’s a lot of 85+ dudes and that is good to know. I hear you about rapa and I did mention you as being a very good N=1 now let’s try and find few more N=1’s hopefully over 95 that are taking Rapa LOL. Not against Rapa whatsoever, just mentioning that I’ve had every now and then the known side effects. Will see as we go along.
To be honest, I haven’t seen any comments from the usual critics who often pick apart papers. I know the unspoken rules of the forum go without saying, but I still feel the need to say a few words.
On subjective benefits:
In a non‑blinded survey, when subjects actively seek out, purchase, and take a widely hyped “anti‑aging miracle drug” in pursuit of longevity, a strong placebo effect and confirmation bias are inevitable. Under the current study design, these purely subjective measures have virtually zero objective medical value.
On the COVID‑19 data:
Infection rates were essentially the same between the two groups. As for disease severity, the “continuous treatment” group, which the authors highlight as having the best outcomes, consisted of only 37 people. If you look closely at their statistical methods, that neat p < 0.005 in the 37‑person group came from lumping together “moderate,” “severe,” and “long COVID” cases and comparing them against the non‑treatment group. Break it down: severe (0 vs 2) or long COVID (0 vs 3) – the sample sizes are so small that no statistical significance can be calculated at all.
If this comparison were meaningful, the fact that the continuous‑use group had a significantly higher proportion of mild infections (86.5% vs non‑users, p < 0.005) would imply that taking rapamycin increases the likelihood of mild COVID‑19. But that’s absurd.
Bottom line:
The study design has fatal flaws; it cannot yield any valid conclusions. And let’s be blunt – people who go out of their way to get a rapamycin prescription from Alan Green at a New York clinic are inevitably more aggressive in their anti‑aging and medical approaches. Confounding factors are nearly impossible to control.