1. Primary and Secondary Efficacy Data: Functional Performance
Primary Outcome (30-Second Chair-Stand Test): * Intention-to-Treat (ITT) Analysis: Both groups improved, but the rapamycin group completed an average of 2.13 fewer repetitions compared to the placebo group at 13 weeks (p=0.089).
Per-Protocol (PP) Analysis: Among participants who strictly adhered to the exercise and dosing schedule, the negative impact was statistically significant, with the rapamycin group completing 3.44 fewer repetitions than the placebo group (p=0.007).
Objective Takeaway: The data demonstrates a clear, negative dose-response relationship: strictly adhering to the rapamycin regimen resulted in significantly worse lower-body functional improvements compared to exercise alone.
Secondary Functional Outcomes (6-Minute Walk and Grip Strength):
The rapamycin group walked an average of 4.87 meters less than the placebo group.
Grip strength in the rapamycin group was an average of 1.13 kg lower than in the placebo group.
Objective Takeaway: While these specific secondary differences did not reach statistical significance (p>0.3), the directional trend is uniform across all physical metrics: rapamycin produced inferior functional outcomes compared to placebo.
2. Biological Aging and Systemic Inflammation Markers
Epigenetic Clocks (DNA Methylation):
Measurements across multiple epigenetic aging clocks (e.g., GrimAge, SystemsAge, OMICmAge) showed mixed, negligible differences between the groups that were not statistically significant.
Systemic Inflammation (C-Reactive Protein):
The mean CRP level in the rapamycin group increased by 4.26 mg/L compared to placebo (p=0.152).
This numerical increase was entirely driven by two extreme outliers in the treatment group (17 mg/L and 50 mg/L).
Objective Takeaway: There is zero quantitative evidence in this 13-week timeframe that 6 mg of weekly rapamycin reduces biological age or systemic inflammation.
3. Safety, Adverse Events, and Metabolic Data
Adverse Events (AEs):
While 85% of participants in both arms reported at least one adverse event, the total volume of events was notably higher in the rapamycin arm (99 events) compared to the placebo arm (63 events).
Events adjudicated as “possibly or probably related” to the drug were more than twice as frequent in the rapamycin group (35%) compared to the placebo group (15%).
The only serious adverse event (SAE) in the trial—a case of community-acquired pneumonia requiring hospitalization—occurred in the rapamycin arm.
Laboratory Safety Parameters: * Glucose Metabolism: Rapamycin caused a statistically significant increase in HbA1c (+1.74 mmol/mol, p=0.030).
Lipid Metabolism: Rapamycin caused a statistically significant increase in LDL (“bad”) cholesterol (+0.32 mmol/L, p=0.036).
Hematology: Rapamycin caused a statistically significant decrease in Mean Corpuscular Volume (MCV) (-2.90 fL, p<0.001).
Objective Takeaway: Beyond mere symptoms, the bloodwork objectively proves that 13 weeks of weekly 6 mg rapamycin induces measurable degradation in lipid profiles, glucose regulation, and red blood cell parameters in this demographic.
I hear you, but apparently, it either didn’t help him much (but he thought it did), or it wasn’t enough help. Either way he’s dead and he was taking RAPA. Not good in my books regardless of what anyone thinks. I definitely need to see cases of people being in their late 90’s and hopefully 100’s that seem relatively healthy and have been take RAPA for a while to be convinced. Until such time count me as being very sceptical, while I am still taking it though, which is to say I’m not against it yet. But instead of being say 100% pro, I’m more like 60-65 pro and 35-40 against. Everything else I take I’m 100% pro, not even a 1% doubt that I’m benefiting (greatly) by taking them.
Again, I think Rapa is a perfect case of reward vs risk. For some people there seems to be no risks (or very low) for others there are risks of lipid and glucose moving in wrong direction plus infections and other sides. I always love it when I take something and don’t feel any negative side effects while reaping the benefits. and, for people with no side effects from RAPA I do think they are benefiting from it overall. But if you happened to have to take other meds to counter the side effects of RAPA as an example (or any other med for that matter) then to me it beats the purpose. Why not stick with the substances/meds that you know are not negatively affecting you, yet they are benefiting you greatly with better markers, while still showing pretty convincingly longevity benefits, i.e. SGLT2i’s, Acarbose and many others.
Again, I don’t call it a gamble at all if I take something and have ZERO side effects while the benefits show right away in the labs. As I said earlier been taking Empa, EZE, Telmi, Pita, ACA, and meftormin all of which have shown to increase lifespan (some more, some less) and I have absolutely no negative side effects. I love them! As far as RAPA, well can’t say I love it. One thing is for sure that If I get one more cold/flu case with symptoms near or as bad as last one I had couple weeks ago (it started two days after taking my Rapa dose) you can rest assured that all my 1000 pills of RAPA will be thrown in the garbage, but being that I’m a bit of vengeful type of guy, I might actually burn them first, and to NEVER look back at it again LOL. No, thank you I’m not going to continue taking something that continues to make me sick, and If I were to continue then I’d agree with you, that is pure gambling. As far as the other 5 or six I listed earlier and I love don’t see much gambling there. Even my anion GAP (whatever that is) that has persistently been higher for last five years dropped to “optimal” out of nowhere and i didn’t even expect it at all on my last test. Out of convenience, (and maybe a good guess) I dedicate that improvement to SGLT2i/EMPA even though I had started couple other substances at same time and after my last test (i.e. Telmi and Sele) but it definitely wasn’t Rapa because it kept showing as too high even long after I had started Rapa.
Just my unvarnished opinion but in all honesty if I were to have no side effects from it, or if my sides somehow disappear going forward, I will definitely continue using it.
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.
