curt504
#424
I’m thankful for this forum and its breadth of science topics. I take growth hormone secretagog peptides: ipamorlan / tesamorlan / CJC. Which I blood tested found that my IGF-1 jumps from 159 ish to 257 ish a few hrs post AM injection. I did not cycle based on my Monday rapa dose.
There’s too many interactions for me… Maybe I should cycle HGH at the rapa troughs, over the weekend prior to my Monday rapa dose. Brain straining how ot piece this all together.
In parallel there’s similar cycling, possible over loading scenarios for the mitocondria boosing nutricals: urolithin-a, SS-31, MOTSC, SLU-PP-331, methylene blue. Per expert Alex Kikel (on youtube) depending on how functional your mitocondria are, a max dose of each should not be taken together, but cycled, and at what dose? Another guessing game for most anti agers…
Over loading this post; Kikel loves plasmologens for regeneration!!! IE prodrom.com for non food based. High quality raw egg yokes, fish eggs, high quality fatty fish. Or just take prodrom gleia. ;(
Good luck to all, curt
3 Likes
Very interesting why Eric Verdin quit. According to his statements in the Peter Attia podcast, he quit, because he could feel no effects, meanwhile he had some immune suppression based on getting a pimple on the nose on the day or the day after taking a dose of rapamycin. He was ultimately taking 4-6mg once a week. He also saw no impact of any kind from rapamycin on his bloodwork. Remarkably weak reasoning as I see it. Even PA pushed back a little on that reasoning, pointing out that whatever rapamycin was doing did not necessarily have to be felt subjectively. We don’t “feel” the effects of statin therapy, but it definitely has profound impact on CV health. Not showing up in bloodwork, well we don’t know what to look for, it might be something that is not captured by standard blood tests - that’s a known limitation of taking rapamcin for life/healthspan. I may have missed it, but I don’t recall him stating how long he was taking rapa, but length of exposure may also be a factor - for me it took about seven weeks of a 6mg once a week dose to start experiencing effects on exercise capacity and recovery. YMMV.
5 Likes
Where did you hear this from?
Eric Verdin revealed that in his recent interview on Peter Attia’s podcast.
1 Like
OK - so here is an AI summary of the rapamycin-related discussion from this podcast:
Rapamycin is discussed as a promising but complex intervention for aging, with effects highly dependent on dosage, frequency, and context.
Here are the key discussion points about rapamycin from the video:
1. Rapamycin as a Longevity Intervention
- Rapamycin is highlighted as one of the most promising pharmacological interventions for aging, based on animal studies—especially in mice, where it consistently extends lifespan.
- The drug is known for its role as an immunosuppressant in transplant medicine, but at lower or pulsed doses, it may have immune-enhancing and geroprotective effects.
2. Dosage and Frequency Matter
- The effects of rapamycin on the immune system and aging are highly dependent on how it is administered:
- High, continuous doses (as used in transplant patients) are immunosuppressive.
- Lower, intermittent (pulsed) doses may enhance immune function and improve vaccine response in older adults.
- A clinical trial (the Manick trial) showed that a weekly 5 mg dose improved vaccine response in older adults without the side effects seen at higher doses.
3. Human vs. Mouse Data
- While rapamycin works reliably in mouse models (even when given continuously in food), translating these results to humans is complex.
- Mice and humans differ significantly in their baseline biology and environment, so results in mice may not always predict human outcomes.
- The speakers caution against over-reliance on mouse data and emphasize the need for more primate and human studies.
4. Mechanisms and Uncertainties
- Rapamycin’s benefits may be linked to its effects on autophagy, inflammation, and possibly reducing senescent cells, but these are hard to measure directly in humans.
- The drug’s impact on glucose metabolism is also discussed, with some evidence of negative effects at higher doses.
5. Clinical Use and Caution
- The speakers express caution about using rapamycin in younger, healthy individuals due to unknown long-term effects and potential risks.
- For older adults, especially those with signs of chronic inflammation or immune decline, rapamycin might offer benefits, but more research is needed.
- Anecdotal reports suggest some people feel stronger or better on rapamycin, but these are not universal or well-studied.
6. Regulatory and Practical Barriers
- Some promising clinical trials were hampered by regulatory or bureaucratic issues, slowing progress in the field.
- There is a need for better biomarkers to measure the effects of rapamycin and other interventions on immune aging in humans.
7. Rapamycin in Context
- The speakers emphasize that physical activity remains the most robust anti-aging intervention.
- Rapamycin and similar drugs should be considered as potential add-ons, not replacements, for lifestyle interventions.
These points reflect a nuanced view: rapamycin is a leading candidate for pharmacological longevity interventions, but its use in humans requires careful consideration of dose, timing, and individual context, and should be guided by ongoing research and improved biomarkers.
1 Like
Why did Eric Verdin say he quit rapamycin?
Eric Verdin said he quit rapamycin because he did not notice any tangible benefits from taking it.
In the podcast, Eric Verdin explains that he stopped taking rapamycin for several reasons:
-
Lack of Noticeable Effects: He did not observe any clear metabolic, physical, or strength improvements while on rapamycin. In contrast, he noticed measurable benefits (like improved numbers and functional strength) when using GLP-1 agonists, but with rapamycin, he “never could tell whether I was taking it or not.”
-
Caution About Mouse-to-Human Translation: Verdin expresses concern about directly applying results from mouse studies to humans. He notes that while rapamycin consistently extends lifespan in mice, humans are biologically different and already have highly optimized longevity pathways.
-
Potential Risks and Uncertainties: He worries about the unknowns of long-term rapamycin use, especially in healthy, younger individuals, and suggests it may be more appropriate for older adults with signs of chronic inflammation or immune decline.
-
Preference for Proven Interventions: Verdin emphasizes that physical activity and exercise remain the most robust, evidence-based anti-aging interventions, and he prioritizes these over experimental pharmacological approaches like rapamycin.
In summary, Eric Verdin’s decision to quit rapamycin was based on a lack of perceived benefit, scientific caution, and a preference for lifestyle interventions with proven efficacy.
2 Likes
I still say his reasoning is weak. If he is simply conservative, and worries about lack of evidence of long term effects in humans, that’s fine - it means he has low risk tolerance. That position is absolutely legitimate, and completely justifiable. But then… why doesn’t he stick to it? Instead he went ahead and took rapamycin - OK, now that is inconsistent with his position. For example, steroids exceed my risk tolerance. I therefore don’t take them - period. I wouldn’t get on them and then get off using the same information I had access to before I got on them. Eric Verdin had exactly the same information about lack of evidence of long term effects and possible risks before he took rapa, so it’s not like he didn’t know, and then found new info and quit. If he took it because he wanted to see subjective effects - that’s a very poor standard by which to go, in either direction. You may feel nothing, doesn’t mean you get no benefit - absence of evidence is not evidence of absence like in the statin example. On the other side, feeling subjectively good, doesn’t mean heroin is good for you, and seeing “good” effects of steroids doesn’t mean steroids, rapamycin or GLP1-RA have good long term effects without long term human trials showing this. So there is nothing much he could have learned from actually taking rapa, especially short term. Therefore, as I see it, his reasning to get on or off rapamycin is weak. YMMV.
This is not to claim he is right or wrong to get on or off rapamycin. Just that the reasoning he gave for it is not very sound or convincing to this outside observer.
5 Likes
I think the difficulty is that the aging process happens at the cellular level and is quite slow. People function and feel at the somatic level. Hence noticing anything happening at the cellular level is hard. I monitor all sorts of things which do pick up the effect of the aging process.
5 Likes
jnorm
#433
Very interesting why Eric Verdin quit. According to his statements in the Peter Attia podcast, he quit, because he could feel no effects, meanwhile he had some immune suppression based on getting a pimple on the nose on the day or the day after taking a dose of rapamycin. He was ultimately taking 4-6mg once a week. He also saw no impact of any kind from rapamycin on his bloodwork. Remarkably weak reasoning as I see it.
I have a colleague who hung out at the Buck Institute a bit and he told me (and I was shocked to hear) that the scientists he spoke with there there weren’t taking any supplements or drugs for longevity, and that they had a pretty condescending attitude towards drugs in general.
This was some years ago though, so maybe the square attitude there isn’t as prevalent as it used to be.
4 Likes
Of course, if you are relatively young (compared to me at 85) and healthy, why would you feel any positive effects if nothing is broken? Why would you expect to see any significant change in your blood work?
One would expect the effects of rapamycin to show up in later years in the form of greater healthspan. We do not know if rapamycin affects human lifespan. But the increased healthspan would result in a lower death rate for the individuals taking rapamycin, producing an apparent median life extension.
I have been taking rapamycin for almost five years, and I feel much better since taking rapamycin. My blood work is excellent, especially for someone my age. The only negative impact on my blood work occurred when I first started taking rapamycin at large doses. It raised my fasting glucose and lipid levels slightly. I addressed this by taking medications to lower them.
The thing that surprises me the most is how virtually pain-free I am. Even my lower back pains have all but disappeared. In the last five years, as I previously posted, I have had no illnesses. No colds, flu, etc. So I believe this cannot be a placebo effect, and the immunosuppressive effect of weekly pulse dosing is nearly non-existent. You think someone getting a pimple on his nose after taking rapamycin is proof. No more evidence than my N=1 of never having gotten a pimple or mouth sore. It could just as likely be a coincidence or placebo effect because he has been reading other people’s reactions to rapamycin. As many as 30-40% of people will experience a placebo effect good or bad.
It is still way too early in the game for people to stop taking rapamycin because they feel no subjective or measurable effect.
7 Likes
Jonas
#435
Buck since 1999, what have they done?
Jonas
#436
Could you share some specifics on this?
1 Like
I’ve been following this group for 2 years now. I’m still in the planning phase of my potential rapamycin journey.
I’m almost 64. My current conclusion is that starting around 65 years of age and using it for just a few years and then stop might be the optimal tradeoff between benefits, costs and caution, especially until we have human data and especially for otherwise healthy and fit people.
I think this strategy seems to work in mice. Start late in life and take it for a relative “short” period to get most of the longevity benefits
Some here seem surprised that Verdin, a leading longevity researcher, stopped taking rapamycin, but maybe he’s following a similar plan?
2 Likes
When I was up there for the Longevity Summit conference I met a lot of the Buck researchers and many of the younger people were already taking rapamycin. Like anywhere you get a varying view on risk/reward.
6 Likes
Yes, but the key issue here is how long is “short”? The 3 month mouse dosing (for example) might equate to something like 7 years in human terms.
7 Likes
Nick1
#440
One of the reasons BJ stopped Rapa was that he was alarmed that his RHR was up. While we know of little howbhe arrived at that conclusion.
I couple my weekly Rapa dosing with 24-36 hr caloric fast, I never had RHR as low as this now
6 Likes
RHR depends on lots of things and is not purely a sign of aging. I accept that having a low RHR is generally a good thing. However, if I have been binge drinking for 4-5 days and my RHR has crept up (on fitbit) to say 60 I know that is purely linked to the drinking and when I go on the wagon it will drop down again.
1 Like
Nick1
#442
Of course, RHR depends on many factors such as sleep, stress, alcohol(which affect RHR primarily through its effects on sleep), timing and type of meal, meditative practices, medications ( beta blockers, vasodilators). When l consume alcohol, mine usually is 52-53.
I dont think that BJ deviated much from his Blueprint Protocol. I recall when he announced that he was discontinuing Rapa, he cited rising RHR as the reason. Although he didnt put forth sny plausible link between Rapa and RHR.
So, I had been closely tracking mine to see my RHR is trending up.So, far no indication.
1 Like
I think Eric Verdin’s reasoning is ok, and he explained pretty clearly IMO. He did make the point that the translation of animal studies into humans is pretty poor, which we can hopefully all agree on.
One of the most interesting things he mentioned is the link between body size and longevity. Usually smaller animals have faster life cycles, reproduce quickly etc. Interestingly, humans are a big outlier and we live much longer than we “should” (even biologically/naturally, without medical intervention). He kinda indicated that maybe mice are in a hyper-mTOR activation state, which is normalised by Rapamycin, whereas humans may not be in that state.
So his point is that what applies to mice (inhibiting mTOR, extending life) may not translate to us.
He also laid massive praise onto GLP-1RAs, and said that they are geroprotective.
3 Likes
