Is 5 years of Rapamycin Enough?

I’m very impressed by Matt’s results on mice where short term pulse rapamycin dosing gives impressive long term results. Since I’ve been on rapamycin weekly for 5 straight years, I’m now wondering if it’s time to stop. There are many unanswered questions, especially since we are so lacking in human data.
I will say that at this point I’m not feeling as many positive effects that I did in the beginning, but that may not really matter. I also don’t know how long to stop it, if I should then resume it at some point, and for how long. Such a shame that it’s all such guess work. Should you pulse it, or take it continuously forever like a blood pressure drug?
I realize that no one has definitive answers to these questions but I’d love some opinions.

Have you been tracking longevity/aging markers (DNA methylation, phenotype age, liver and kidney function, full blood biomarkers)?

How else would you know if you’re truly slowing down the aging process?

Have you experienced dosing where side effects are indicated? Lipids, glycemic, other?

“Such a shame that it’s all such guess work”…but it’s NOT guess work I’d argue per above logic.

If my markers were NOT improving, assuming I explored a range of therapeutic dosing regiments, then yes, I’d pause and assess.

Alternatively, I don’t know of another exogenous intervention that has the pan model longevity track record of Rapamycin, so what is Plan B?

And if you changed horses, what would be your “success criteria”?

I don’t know anyone who can rule out cancer as full on all cause mortality risk, THE major inhibitory pathway of mTOR inhibition.

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I would argue that, since the best results in terms of lifespan improvement, has come from lifelong administration of rapamycin starting in early adulthood (equivalent to age 20 to 30 in humans), at higher levels, the probability is low that you have reached maximum benefit from rapamycin from 5 years of taking rapamycin at lower levels (I’m assuming this obviously - since I don’t know your dosing history over the past 5 years).

See Cohort 5 results in the ITP Study summary below (click to enlarge the image below) - with dosing of 42ppm/day, starting at 9 months, with 28% (f) and 22% (m) median lifespan improvement, as the key data point.

The short term pulsed dosing that has been done on mice with good results were at extremely high levels - 8mg/kg, daily… and I doubt that you (or anyone) have been dosing at anywhere near that level for the past 5 years…even considering the typical dose equivalency calculations of dividing the mouse dosing by 12.3 per this paper.… which equates to around 30mg/daily in humans.

Additionally, Dudley lamming has suggested that the interval dosing period in mice in the most recent study… that was used is equivalent to perhaps 20 years in human terms - so again, you (and most of us) are taking much lower doses, much less frequently (weekly, for most), for much shorter periods of equivalent time compared to the mouse studies (6 months in mice equal about 20 years in human terms) :

Now - another way to view 5 years on Rapamycin is that you’ve probably gotten some significant benefit, you aren’t seeing significant additional benefit that can be measured right now, and as a risk avoidance strategy you may want to take a few years off to let the science (specifically the dog studies) to progress and get published before you continue with rapamycin dosing. Everyone has a different risk/reward profile and that would seem to be a reasonable conclusion for some people to make, though my decision might be different.

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After 40 years as a practicing internist I’ve pretty much lost faith in lab results for asymptomatics. I go more by how I actually feel and I sort of feel like the effects hit a peak and then plateaued out at about a year. This would correspond with Matt’s findings that you can pulse it and stop it.

When I started with Alan Green 5 years ago, I was very skeptical. I had exercised daily for most of my life and had never taken a medication for any reason. We started at just 3 mg per week and I have to say that after 3-4 months I felt GREAT. My stamina improved markedly and I felt generally younger. No doubt about it . The benefits, as you say , were substantial.
It’s probably not realistic to continue to see improvements, but there are occasions when drug holidays kick the effects back in gear again. Don’t get me wrong, I still feel good at 67. Apparently my eyes are that of a 40 year old and I can still play basketball and hike with my 30y/o son. I’m not complaining, but I’m like that addict that wants that original feeling back.
But Rap, your arguments are strong ones and they’re swaying me to continue taking it.
Thanks

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There is also the argument that rapamycin can help lower longterm risk of many different cancers… which is perhaps the biggest risk we all face as we get older. It seems likely that ongoing use of rapamycin will help reduce this risk, at least from the papers I’ve seen.

Rapamycin for Cancer Prevention

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I am just starting…9 weeks…but have thought of when I might stop or pause as some of the protocols do. Kind of do not think I will do either. The safety profile and history of rapa seems good and we know half life and how to adjust dose to keep trough levels low.

I have not had my bloodwork done and will have it done at my regular physical in 2 months. If nothing seriously amiss I will not test again for another year. if something jumps I will do as needed. But to solve a problem not to track month to month. I think blood work is great, but not the be all and end all that some think. I like my Doc because he thinks through them and me and its sometimes a compromise…

I think assessing the specific anti-aging effect are very difficult…near impossible and certainly looks even more complicated by the range of dosing that rapa appears to have positive effects on health related issues. For certain, if you are taking 8 mg weekly and seeing results in obvious health parameters would 20 mg be even better and reach some hidden ones that are less obvious and maybe not even picked up by pretty intensive blood work? Very possible but I can live without that.

For me (and everyone is different…goal wise and “reaction to rapa” wise) I am here primarily to improve health parameters…care a lot less about ultimate aging extension. I have no major known health problems…but do need to lose 20 lbs., deal with allergies, have some periodontal issues, and old man aches and pains. These are my markers and I do not need blood work to all me if I am getting there. Easy to measure. Logic tells me that if rapa deals with these it is working s I am not radically changing my lifestyle or taking stacks of supplement or drugs. OK, maybe not working hard enough to scare everything away, but likely will extend age because those things I can measure help people live longer. So, in time I may increase dose just as insurance, but unless something is shown with real data, not individual self measurement and amateur vodoo analysis I probably will not. I might miss out on a few years. But then again, maybe I get knocked down by a stoke or a bus and I don’t get my rapa money back.

So far I see some help in some benign facial skin lesions, a few less aches and pain (this one could be a mind-fuck too), and the biggest…just seen 3 days ago… a much diminished pollen allergy. Dramatic…just like on/off switch. From a 9 on 1-10 scale to a 3. And this is peak allergy season are (11.5 on 12 point scale). no big energy changes or weight effects…I am told by folks on here to see some weight help in another month. My dentist is monitoring a perio problem and while that seems to be stable too soon to tell.

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Can you see if you have a cancer inside of you?

And if NOT, awesome. The genetic lottery, lifestyle, Rapamycin?

Cancer scares me the most…I can exercise for both CVD and brain health benefit, but how can I change gene expression to improve DNA repair, or inhibit wonky proliferation, or improve autophagy?

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Of course you cannot see cancer inside of you…mostly. But even if you could spot it today it could be lurking beyond detection and kill you in a short time.

I agree rapa is the way to go, but is 10 mg a day enough or is 45? I think that is the real issue for people who believe it works, not all or none or all the time or never.

At this point in time you are seeking too much from anything and worrying about something you really cannot solve with the tools at hand.

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Agreed, cancer scares me the most also. I’ve seen far too many patients die from it. Also, I got a zero on a coronary calcium score which put my mind at ease on that one.
In that vein, I heard a Peter Attia podcast a few years ago on a cancer screening device called Prenuvo.

It’s an MRI advanced technology that picks up cancer as small as 1 cm. Very curable even for pancreas/ lung/ ovary, etc.

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Wow…price is certainly reasonable.

I am going to dig a bit and check it out.

Now I can worry about not getting one. Always something.

Haha. Yeah, that comment is priceless. Always something.

Here’s another potential cancer screening test to consider:

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@ rivasp12

Thanks for sharing the Prenuvo link, sounds like a great tool to do cancer screening! They have a site opening up in my area this spring.

MRI is generally not as high sensitivity/specificity as PET/CT, but uses no xrays.

If one is to live an extended lifespan, they must “escape” the chronic illnesses that most people die from in old age. This is how centenarians reach a 100.

Until we have magic pill interventions, prevention is critical. In cancer and CVD, if one can diagnose very early, the chances of a curative intervention are far higher, allowing one a higher chance of “escapism”

I’ve had a volumetric brain MRI, Coronary Calcium, and thinking about a PET/CT scan for prostate cancer this summer (and I can get a relatively very lost cost test done at an academic institution) They are generally prohibitively expensive outside the funded/insured system. My dad was diagnosed with Prostate Cancer at 57, and although his treatment delayed his death, it came with side effects, and he still passed at 79. His diagnosis puts me at higher risk, and although my prostate markers do not indicate anything untoward (Urologist on my care team), I am being proactive at 57.

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@ brandy111

Another great suggestion.

“It’s able to detect about 50% of cancers in people ages 50 to 79 whereas our current screening only picks up about 15%, so that’s another 35%,” said Dr. Suresh Nair with Lehigh Valley Health Network. Grail says the test is also finding signals related to aggressive cancers that currently lack screenings, like pancreatic cancer. The Galleri test is available by prescription. It costs $949 and is not covered by insurance."

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No doubt that liquid biopsies are the wave of the future in early cancer screening and detection. After prevention, early detection is most important.

@ rivasp12

Did you learn anything further about the Early Detect screening product?

No, but I’ll call them again tomorrow.

Congratulations Mac, it takes a lot of research and guts to be as proactive as you are. Prostate cancer drives me nuts because the studies are very conflicting and PSA screening is so controversial.
Prevention is always key and so I think rapamycin is very important . Maybe exercise. Maybe green tea. Maybe a healthy weight.
Definitely has a genetic component so you’re smart to not just ignore it.
Ten years ago my PSA was 3.5 and now at 67 it’s 4.5. I checked a free percent PSA and it’s 23.3 ( not bad but over 25 is ideal) . Also got a prostate health index score which is 34 ( ideal under 35). All ok but not great. FH of uncle with prostate cancer.
Now I’m contemplating MRI, which at Hopkins is pretty decent.
My biggest pet peeve is that prostate cancer , after biopsy, is given a Gleason score. The range is 6-10. A score of 6 is essentially a histology diagnosis but it really doesn’t behave as a clinical cancer. It shouldn’t even be called cancer. The designation just scares men to death.
Same with basal cell skin cancer. Worry about melanoma.

Cancer prevention is probably the thing I love the most about rapamycin. The evidence keeps growing. That, along with really good early detection, will soon make cancer preventable and detectable.

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I think this is a trap that many may fall into is that they try to gauge antiaging based on feeling well, because its more true that someone can base health and fitness on feeling well. You can even base healthy longevity somewhat on feeling well. But if a person has a goal of extreme anti-aging then the wellness & health feeling becomes a very weak metric. Sometimes things that are antiaging make a person feel less well and even lower energy.

It all depends on what person’s goal is , is it decent longevity and health? or to extend life as much as possible (perhaps with the intention of future therapies that may grant additional anti-aging). The risks and sacrifices to each approach may differ.

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