It’s not true.what’s your source?We can’t even detect rapamycin in the brain.and yet the clains about it are getting more and more diciculous.
According to Matt Kaeberlein… it doesn’t have to cross the BBB to be effective. It can work on inflammation peripherally around the brain. And, influence the hippocampus… and reduce Alzheimer’s effects.
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I don’t want to get side-tracked. is there any trial demonstrating that rapamycin restores HV?
This forum probably has the most rapamycin-obsessed people around, yet a ton of them don’t even pay attention to human clinical trials. But somehow they can just make up benefits like restoring hv. It’s ridiculous.
I’m not even talking about human studies. Just one paper showing restored hippocampal volume in mice would be enough to make it remarkable.
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I don’t know about HV. For me that is sort of getting down into the weeds. I don’t worry about anything that I can’t easily measure.
Yes, an anecdotal report from an N=1, 85+year-old.
Rapamycin has been an extremely rejuvenating experience for me.
You can trace my posts back to 2022 in the threads.
When I started rapamycin ~5 years ago, I was still mobile, but I had to use a cane or walking stick. I had many joint pains. I was seeing my dermatologist four times a year to treat actinic keratosis. I am now pain-free, not a joke, and my actinic keratoses have cleared up. I haven’t seen a dermatolist for two years. Also, I have caught nothing—no Covid, no colds, and no flu—for the last five years.
The protocol I follow is from the early days. One suggested by Dr. Blogosklonny: high pulsed doses. At first I sometimes had diarrhea from the high doses. I titrated down to the highest weekly dose that didn’t cause diarrhea. I have never had any of the other side effects that some mention, like acne or mouth sores. Currently I am on a two-week protocol.
Where I think the disconnect that commonly occurs, as in the mouse studies, the effects of rapamycin were dramatically more apparent in the old mice.
Younger people expecting to see results from rapamycin will just have to take it on faith at this time. If it’s not broken, there is nothing for rapamycin to fix except for delaying aging.
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It’s true. Again, extensively discussed on this site. However, major limitation - this is only true for ApoE4 carriers - no effect in ApoE3 carriers. The most shocking part - how fast it happened. But again, please locate the multiple threads discussing this, otherwise again it’s all over the place. Anyone studying rapamycin should have already been well aware of these. Like:
Short-term Sirolimus Treatment Restores Hippocampus and Caudate Volumes and Global Cerebral Blood Flow in Asymptomatic APOE4 Carriers Compared with Non-carriers
https://alz-journals.onlinelibrary.wiley.com/doi/abs/10.1002/alz.092991
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Researchers at the University of Missouri gave a low dose of sirolimus (rapamycin), an FDA-approved mTOR inhibitor, to a small group of cognitively normal middle-aged adults for four weeks. In the three participants carrying APOE4, the strongest common genetic risk factor for late-onset Alzheimer’s, the drug increased hippocampal and caudate volumes and raised global cerebral blood flow toward the levels seen in non-carriers. The two non-carrier controls showed no such change. No side effects and no disturbance of blood glucose or HbA1c were reported. The result is a provocative proof-of-concept, but the sample is tiny (n=5 total), uncontrolled by placebo, and reported only as an abstract.
For decades the APOE4 gene has been a sentence read out early. Carriers, who make up roughly a quarter of the population depending on ancestry, show measurable brain atrophy and reduced blood flow years or decades before any symptom appears. The prevailing view has been that this slow structural erosion is a one-way street. A new pilot study out of the University of Missouri suggests, cautiously, that at least some of it might be reversible with a drug already sitting in pharmacies.
The drug is sirolimus, better known to the longevity field as rapamycin. It inhibits mTOR, a master nutrient-sensing switch, and in doing so switches on autophagy, the cell’s recycling and quality-control machinery. Rapamycin extends lifespan in mice more reliably than almost any other intervention, which is why the aging-research community watches every human trial closely. Here the team gave just 1 mg per day for four weeks, a low, short exposure by design.
The big idea is targeting. The researchers did not treat everyone equally. They stratified by genotype and found that the benefit appeared specifically in APOE4 carriers, the people who started with lower hippocampal volume and lower cerebral blood flow than their APOE3 counterparts. After four weeks, carriers showed increased volume in the hippocampus and caudate, structures central to memory, learning, and emotional regulation, and higher global cerebral blood flow. The non-carriers, who had less to correct, did not change. In effect the drug appeared to nudge the high-risk brains back toward the profile of lower-risk brains.
If this holds up, the implication is a preventive strategy aimed at the highest-risk group before symptoms begin, using a cheap generic drug. That is a genuinely attractive proposition, because almost nothing in Alzheimer’s has worked at the prevention stage.
But restraint is essential here. This is five people. There was no placebo arm, the carriers and non-carriers were not matched, and four weeks is far too short to know whether a volume change reflects real neuroprotection or a transient fluid, perfusion, or measurement effect. The work has been presented as a conference abstract, not a peer-reviewed full paper, and no raw numbers or variance estimates are given. The signal is interesting. The evidence is preliminary. Both things are true at once.
Dosing Used: 1 mg per day, taken orally, for 4 weeks. The abstract describes it as “low dose Sirolimus (1 mg/day).”
- Publication type: Conference poster abstract (AAIC 2024), published in a supplement of Alzheimer’s & Dementia. DOI 10.1002/alz.092991. Alzheimer’s & Dement. 2024;20(Suppl. 2):e092991.
- Lead author: Abeoseh Flemister. Corresponding author: Maalavika Govindarajan. Senior investigator group includes Ai-Ling Lin, whose lab works on APOE, brain metabolism, and rapamycin.
- Institutions: University of Missouri, Columbia, Missouri, USA (primary site), with collaborators at University of Kentucky, Rush University, and Siemens Healthineers.
- Country: United States.
- Journal: Alzheimer’s & Dementia (the flagship journal of the Alzheimer’s Association, published by Wiley).
- Impact evaluation: The impact score of this journal is approximately 14.0, , therefore this is a High impact journal.
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Put one more study down for the effiacy of the 1mg/day dosing regimen.
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Can’t find anything that supports this directly, lots of mechanistic “potentials”
rapamycin ESTORATION OF HIPPOCAMPAL VOLUME use onl.pdf (682.6 KB)
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https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.094114
To be honest this was a while back and I saved it in a file. I did not re read the article before sending. Just wanted you to know where I got that idea and to my recollection someone had asked why people bother. Quotes from the conclusions:
APOE4 carriers had significantly increased Caudate and Hippocampal volumes (Fig. 1A) and gCBF (Fig. 1B) after 4 weeks of Sirolimus treatment. These differences were not found in the non-carriers (APOE3 participants). The quantitative data is shown in Table 1. It also shows that APOE4 carriers had significantly lower Hippocampal volume and gCBF at baseline compared with that of APOE3 participants (indicated by “**”), and Sirolimus tends to restore the values to closer to those of the non-carriers. No side effects were observed, and no changes in blood glucose and HbAc1 levels were found in all the participants.
Conclusion
We show that short-term Sirolimus treatment can effectively restore brain volumes and gCBF for asymptomatic APOE4 carriers.
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I’m here for educational information not harrassment or disrespect. I have enough of an education to read and understand research and decades of clinical work to boot. But I am just one person who started out knowing nothing about this topic, which is very, very deep and far-reaching. If I am in error there is a much more professional way to let me know. I know there were only 5 humans but they were humans and not rodents and I kept reading and listening for more. There have been more human studies and Arizona State just funded a new larger one. I watched an interview with the more recent study and nobody had any bad side effects and people who did get canker sores did not want to report b/c they felt so good on rapa they were afraid they would be put out of the study. I have seen a lot and there have not been harmful effects when people stayed on protocol. That is all I know and trust me I will be very careful before I think about sharing anything more on this site. Life is hard enough. You need to lighten up.
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I did not claim they found rapa in the brain.So your conclusion that “claims …are .getting more and more ‘diciculous’” as you put it, I guess is an accurate statement. The study measured the volume of the hippocampus and re-measured after short term, low-dose rapa. They were numeric values.
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Exactly. It works at the cellular level. It is not said to race to the brain. It helps turnover of senescent cells and encourages autophagy.
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The problem is that I cannot access the full article to check any references, this is a 2 page open article with very little good evidence. And specifically claimed for 1 type of condition.
If this is all there is to support this hypothesis it’s pretty weak. I’m going to look for more now that we have the basic info.
And there is 1 comment.
1 Salix songarica
comment accepted March 2025
I find the distributions of datapoints in Fig. A puzzling.
In hippocampus, the baseline and post distributions look the same. I annotated the screenshot below with an overlay showing this (green circles are overlaid over blue squares).
Estimating the values using an online data-from-graph tool, I got baseline (left-to-right): 2992, 3180, 3836 (mean = 3336, vs. 3336.77 in table); post: 3465, 3653, 4301 (mean = 3806.33, vs. 3806.33 in table). By trying possible pairings in one-sided (or not) paired t-test or Wilcoxon tests, the datapoints seem to be paired (baseline & post of each individual) as such: 3–1; 2–2; 1–3. In this order, a paired and one-sided t-test indeed gives p = 0.025 (vs. 0.024 in table; other options are much further). As it gives the expected p-value here, I will assume below that the authors used one-sided paired t-tests. The authors unfortunately did not report the statistical test they used.
In caudate post-sirolumis, one (of three) datapoint seems to be precisely on the mean, and the two others be symmetrically distant from it (which must automatically be the case if a datapoint is exactly the mean, my surprise is specifically that one datapoint of just three is precisely the mean). With a bit of algebra using the mean and SEM given in the table, one can back-calculate the three datapoints (bottom to top): 2265.29; 3050.77 (the mean); 3836.25. Thus, the distances from the mean for the top and bottom datapoints are both exactly 785.48 (3050.77 minus 2265.29, and 3836.25 minus 3050.77).
I estimated the caudate baseline datapoints using the online data-from-graph tool: 2089.6, 2770.1, 2986.1 (mean = 2615.27, vs. 2615.32 in table). Assuming I found the type of test the authors used above, I cannot replicate this p-value. With one-sided paired t-tests, the smallest p-value is with baseline/post datapoints being paired in the same order (1–1; 2–2; 3–3), giving 0.087, which is close to double the p-value reported (0.087/2 = 0.0435, vs. 0.044 in table). Perhaps the authors incorrectly divided by two another time to obtain the “one-sided” p-value? This would be incorrect. The “two-sided” p-value is 0.17, which is (correctly) divided by two (0.087) when it is one-sided. 0.043 (or 0.044) would amount to divide it by four.
Could the authors help me understand these data distributions and the caudate baseline vs. post p-value? With regards to the data distributions, perhaps this kind of data is much more discrete than I imagine (I am not an MRI expert). I could also not be using the correct statistical test.
Thank you in advance!
Here is what Perplexity found, some good info.
are there any similar articles or studies on this.pdf (455.2 KB)
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I wonder how many apoe4 carriers on rapa have had brain MRIs?
I had it done at Simon One, but it was after starting rapa. Too bad it was not prior to starting.
I’m not planning to spend $$ on another one any time soon, but it will be interesting to see if there is an improvement, if small changes are even reliable.
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