This is amazing news
1 Like
The dosing is disappointingly low (which I believe may minimize the results they see). Everolimus is roughly equivalent to 2/3 of a dose of rapamycin, so its like taking rapamycin at 3mg or so for 24 weeks. I’m sure they did this to minimize risk as seen by their IRB, but I’m not sure they will see much in the way of results at that dosing level for 24 weeks. I hope I’m wrong.
Drug: Everolimus 0.5 MG once per day
Drug: Everolimus 5 MG once per week
4 Likes
Remember that these are 2 of the 3 doses successfully used in the original Mannick trial, with 5 mg once weekly as the best of the crop.
1 Like
Very exciting in general. Look forward to seeing what they find around this:
Also wonder how they will be doing that and whether perhaps non trial participants could do such testing somehow?
There was a thread on this{testing mTORC1]
If you did not see, review link below;
1 Like
I have posted before cost is around $4,000 to do each test.
All standard off the shelf equipment.
All out of pocket payment.
Not willing to spend $8k for two test.
2 Likes
Wow, yeah, not me either.
Seems like a business opportunity for someone to run with as more and more people around the world are taking up rapa…
Yes - for the immune response and for side effect profile. Given the “higher is better” results of rapamycin dosing in mice longevity studies, I have to suspect that the optimal dosing for rapamycin for longevity is higher than the optimal dose may be for immune response in the short term. But as with so many things, we really lack clarity on this from a research perspective.
2 Likes
1 Like
Rapamycin shortens lifespan in mice with diabetes:
https://academic.oup.com/biomedgerontology/article/71/7/850/2605132?login=false
I don’t think it will work - they got participants that are the worst candidates for Rapamycin
2 Likes
“The objective of this project is to determine if mTORC1 inhibition by 24 weeks of daily (0.5 mg/day) or weekly (5 mg/week) everolimus can safely improve physiological and molecular hallmarks of aging in humans. [86] Participants who are 55-80 years old and insulin resistant or prediabetic will be randomized to treatment and can expect to be on study for up to approximately 38 weeks. Participants aged 18-35 will not receive the intervention and can expect to be on study for up to approximately 8 weeks.”
The dosing, timespan, and participants make this appear to be a weak trial. Hopefully, it won’t produce negative results for this participant group, but that may depend on the tests being given.
4 Likes
I’m puzzled as to why people this trial seems like it won’t “work”. Are people worried about negative results? Negative results are still useful. Are people worried that there won’t be much difference between the medication and placebo? That seems unlikely, but still useful .
I’m just happy this study doesn’t involve mice for once. Don’t let the perfect be the enemy of the good here.
1 Like
There are some problems with that study:
-
- Rapamycin in mice with diabetes SHORTENS lifespan - here they choose people with prediabetes. Rapamycin increased lifespan in 90% types of mice, but not here - they choose type of people that will respond the worst
-
- They measure blood chemistry, blood cell counts, lipids, glucose, and insulin - all of this is impaired in mice with Rapamycin - even though Rapamycin extends lifespan in normal mice, it still causes high glucose, high cholesterol, low blood counts - so they measure traditional “markers of health” - all of this probably will be worse (based on studies on mice)
- Rapamycin is for now the best drug in mice for lifespan extension - but this is study has very low probability of success - I don’t know why they didn’t add Acarbose or Metformin - it had better results in mice than Rapamycin alone - Acarbose removes high glucose from Rapamycin
Also, just compare this 2 survival curves for male mice (14 ppm Rapamycin + 14 ppm Rapamycin + 1000 ppm Acarbose):
https://phenome.jax.org/itp/surv/Rapa/C2009
https://phenome.jax.org/itp/surv/RaAc/C2017
- Good thing is that they measure: epigenomics, transcriptomics, proteomics, lipidomics, and metabolomics - but the problem is that most clocks don’t show any difference in Rapamycin treated mice in blood - most epigenetic clocks showed that Rapamycin doesn’t slow down epigenetic clock in blood (it had some effect on liver and some other tissues but not blood)
2 Likes
All your evidence points to mice studies. Human studies might or might not replicate results found in mice. In either case, it will be a useful data point going forward.
We have a lot of mice knowledge. We need more human knowledge.
Usually when you design clinical trials you design them in a way that maximizes the probability of “positive” results - i.e. the results you hope for. The concern i have is that the Institutional Review Board is likely extremely risk adverse and so has forced Adam to accept the shortest time period and lowest dosing protocol. Unfortunately that lowers the probability of success. And if it fails then more clinical trials are less likely.
4 Likes
Thanks for the explanation, that makes sense.
Anyone who wants to learn more and is considering everolimus instead of rapamycin, see this thread here: Everolimus instead of Sirolimus / Rapamycin? Anyone else trying?
I do share this concern: whether you look at blood levels or convert doses based on metabolic rate, the animal studies suggest that even standard clinical doses may not be enough, let alone these. I expect that they were (a) trying to replicate a positive previous result, and (b) being conservative with safety for the IRB and maybe the NIA, and (c) thinking of real-world translation: many people on this forum are willing to put up with a lot of side effects and non-trivial risks, but the average aging person likely won’t — especially since we’re never going to get a lifespan study and may never get one with hard outcomes.
I’ll spell it out: if the results are indistinguishable from placebo (=negative), then we won’t know if the dose was too low or if it just doesn’t work. We would really like to know the difference 
. And after a negative result, neither the NIA nor anyone else is likely to pony up the rather large amount of money it will already have taken to run this first trial just to give it another go at a higher dose.
That’s a very good point. On the other hand, the mouse model in the study you’re referencing is the db/db mouse, which develops quite severe diabetes and obesity and is extremely short-lived (" The median survival of male db/db mice fed the control and rapamycin diets was 349 and 302 days, respectively, and the median survival of female db/db mice fed the control and rapamycin diets was 487 and 411 days, respectively."). It’s plausible that people who are only slightly insulin resistant might respond differently. I wish we had more rodent data on this question.
To play Devil’s advocate a bit, 72% of the US population is overweight or obese, and 48.8% of adults over the age of 65 are prediabetic, so it would be unrepresentative not to at least have a lot of prediabetic people in the trial.
There are safety signals they will need to monitor. In the original Mannick trial and other studies using these doses nothing too awful happened on basic CBC and clinical chemistry; provided that happens again in this larger study, having the bloodwork be broadly consistent with what’s seen in the mice will be evidence of translatability.
That would introduce serious confounding: scientifically, you’d really want to go step by step. Also, the acceptability of acarbose by Americans is low (GI issues), and the doses used in the ITP are really pretty astonishing and unlikely to be translated.
Would you please identify your source for this?
2 Likes
It looks like there is a follow-on study being done at the University of Wisconsin, by Adam Konopka and the team there. If you live in the area, I recommend you join the study. We need much more data on rapamycin in healthy people, so I’m glad to see this research being done (and still funded).
Can Rapamycin slow aging?
Overview
As people age, the risk for developing chronic diseases and conditions increases. The FDA approved drugs rapamycin (sirolimus) and rapamycin analogs (everolimus) increase the quality and quantity of lifespan in animals. It remains unknown if the same could be true for humans. The purpose of this research study is to learn if the rapamycin analog everolimus can help improve or maintain the health and function of adults 55-80 years old who may have insulin resistance or pre-diabetes. As a part of this study, you will be asked to take low doses of everolimus or placebo once daily and once weekly for 24-weeks. There will be several assessments before, during and after the 24 weeks. These include blood and muscle sampling, and measurements of body composition, metabolism, exercise capacity (VO2max), and brain and heart health. All visits are located at the University of Wisconsin- Madison campus and you will be compensated up to $2000 for your time.
You May Qualify to Participate if you meet the following:
- Are between the ages of 55-80 years old
- Are not taking medications to lower glucose or that prolong bleeding
- Have pre-diabetes or insulin resistance, but are otherwise healthy
- This would include an elevated fasting glucose (100-125 mg/dL) or HbA1c (5.7-6.4%). If you do not know if you have values consistent with pre-diabetes or insulin resistance, we can help determine this for you at no cost.
Participants Will:
- Take a pill once daily and once weekly for 24 weeks
- Be monitored by physicians and study team before, during, and after the course of the study
- Complete a variety of health tests as shown in the Study Schematic below.
- These include exercise testing, blood and muscle sampling, heart and brain imaging, glucose testing and continuous glucose monitoring (CGM), and a body composition scan (DEXA Scan)
- You will be compensated up to $2000 for your time!
https://konopkalab.medicine.wisc.edu/clinical-trials/everlast/
And a local (Wisconsin) news story on the study:
Could a drug slow aging? UW-Madison researchers seek answers in trial
University of Wisconsin-Madison researchers are studying whether a drug used for organ transplant patients could slow aging in humans.
Some compelling evidence in recent decades shows rapamycin — also known as sirolimus — can increase the quality and quantity of life in animals, said Adam Konopka, a UW-Madison assistant professor of geriatrics and gerontology.
“This got people really excited that maybe this drug could be used to improve human healthy longevity,” he said.
The New York Times and Washington Post have reported on the growing popularity of people taking rapamycin off-label in an attempt to live healthier longer. While it remains unclear whether the benefits reported in animals could extend to humans, Konopka said he hopes a clinical trial he’s working on will provide more insights.
“I think by the end of it we’ll be able to have a really good idea of whether this drug can have any sort of positive or even detrimental effects for humans,” Konopka said.
Funded by the National Institute on Aging, Konopka’s lab has worked on the clinical trial for the last few years and recruitment wrapped up in late 2025.
“The next six months will be largely focused on completing data collection, and then we’ll move on to a bunch of analysis in the summer of 2026,” Konopka said.
People can still sign up for a related study through Konopka’s lab. Participants may receive up to $600 for completing the study.
What’s unique about your research?
Our trial is a double-blinded, placebo-controlled trial that has enrolled over 84 participants and is testing whether 24 weeks of rapamycin can help prevent the decline or improve outcomes linked to healthy aging.
One unique aspect is that it is comprehensive. We are largely focused on metabolic health, but we’re also studying heart, brain and physical function.
As we get older, I think people can appreciate that those are some of the first things that they start to see change.
Read the Full story here:
3 Likes