Too Much uncertainty?

I’m new to the group, but do appreciate the well-researched and thoughtful information presented on the site.

I’m a very fit and healthy 49-year-old and wanted to begin sirolimus for cognitive and general longevity benefits down the road.

I’m just concerned about potential issues regarding Trem2, amyloid and other “scary” reports recently. There seems to be far more positives, but I’ve worked hard for decades to be in excellent shape and worry about detrimental, unforeseen effects.

Anyone else interested primarily in dementia prevention? Any reservations about long-term rapa usage.

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Hello Ben,

Certainly can understand not wanting to undo the great effort you have put in… fair to be cautious.
For what it is worth after 2 years and 4 months on rapamycin every week - no breaks - (at almost 65 years) memory is sharper, body is more fit and strong and attitude is euphoric.

If you have not heard Dr. Peter Attia (surgeon) and Matt Kaeberlein (clinical aging researcher) YouTube talks (both users started several years ago at 50 years). their caution and confidence might help you.

I think 49 is a great age to start rapamycin - but you are in such great shape - you might not see the full benefits it gives you. I recommend getting a good biological age baseline before starting and see your age. That way if you start on rapamycin in 6 months to a year you can retest and see what your methylation, glycans and other biological markers say. Reversing age, no change or worse. For me it was reverse biological age 14-27 years (depending on the test a simple spit 14 years - blood test 27 years). Pretty astounding and the CEO’s of those companies I used agree - I am not the norm. My only explanation is rapamycin.


Hi Ben, welcome to the site.

Everyone has a different risk/reward profile so I completely understand if people want to wait for more data around rapamycin, or like me start earlier and test it out with the option of pausing if any issues develop. And one of the goals of the site here is to bring together all the information (both academic, clinical and personal experience) so that everyone can make the best decision for themselves.

I think most of us here have an equal or higher priority on mental functioning as physical health. And many of us have family members and / or parents who suffer(ed) from dementia or alzheimers and know we want to do everything to avoid it. Here is a thread regarding this issue: Best Methods for Tracking Cognitive / Brain Health with Age?
Some of us here are taking very high doses of rapamycin precisely for the reason of keeping our brain healthy (@MAC ).

We’ve had a long discussion on the TREM2/Amyloid plaque paper that came out - you can see that here: Rapamycin increases Alzheimer's-associated plaques in mice, study finds

Of course, they’ve been working on the premise that the amyloid plaques cause alzheimers but that really hasn’t panned out using the existing mouse models of Alz, so there are many questions around that entire theory. Additionally, there is, in many people’s opinions, very good data suggesting that rapamycin increases blood flow in the brain and likely helps make the brain more resilient to dementia or alzheimers - see these papers/discussions here: Intranasal Rapamycin Lessens Alzheimer-like Cognitive Decline in a Mouse Model of Down Syndrome

here: Fighting Alzheimer’s with Increased Autophagy via Rapamycin + Trehalose

here: Rapamycin and Alzheimer’s disease: Time for a clinical trial?

here: mTOR signaling as a molecular target for the alleviation of Alzheimer's disease pathogenesis

Anyway - there is a lot of rapamycin data out there so I encourage you to read up, and if you want to wait for even more data, there are many clinical studies coming out that will further add to the data, see these currently active clinical trials for rapamycin, including as treatment for alzheimers:

Here is a Rapa for Alz clinical study: New Rapamycin Clinical Trial at UT Health San Antonio
Here: New Rapamycin / mTOR Clinical Studies Funded By Impetus Grants
Here: New / Active Rapamycin Human Clinical Trials (related to Aging)
Here: Rapamycin Exercise Study Moves Forward: Dr. Brad Stanfield's Study Registered in NZ
Here: Two New Studies on Rapamycin: For Cats and Dogs, Treatment of Cardiomyopathy
Here: PEARL Rapamycin Clinical Trial Update. Dr. Ross Pelton Webinar

So - a lot more data will be coming online in the coming years if you want to wait.

My approach has been to start rapamycin (3 years ago) and do lots of blood work and tracking, and if any issues come up, I can always stop. Right now at my last blood measure my biological age (as measured by the Levine Phenotypic bioclock calculation, and V3) is about 12 to 15 years lower than my chronological age, so everything seems to be going well.

Ultimately, Only you can make the decision that is right for you.


Thanks everyone very much for all the feedback and insight. Finished the bloodwork appointment this morning and the rapa prescription was actually dropped on the doorstep this evening. I’ve been very excited to start this journey, but became concerned the more I scoured the web for naysayers and negative studies. Cognitive health is definitely my number one reason but long term unknown’s always influence me more than just some current bloodwork issues. Those can be fixed quickly, but other changes that don’t manifest themselves until later are always the things that concern me. Anyway, many thanks again for the links and first-hand accounts of your experiences.