How did you get it to include hyperlinks for the papers? What was your prompt?
I came off Rapamycin and caught a virus a month later that took 2 weeks to fully go away. It is quite rare that I get sick so I wonder if coming off enabled this to happen.
This video makes me want to start it up again but maybe just 3mg per week instead of 5mg I was previously doing.
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Same. I am about to be 45, and reasonably healthy (I hope?). Also prioritizing strength + cardio. I’ve reconfigured my plan to dose 6 mg every 3 weeks.
Week 1- Dose 6mg, and for first 3-4 days only focus on cardio (Z2). Lift second half of week like normal. This is probably sub-optimal, but I will live with it.
Week 2 & 3 - Lift 4-6 days/week +Cardio (Z2 + VO2 Max)
Repeat.
Given i am taking it for preventative health measure vs fixing something (at least that I know about), I figure this give me the best mix. But reality is, I am not sure if anyone knows.
If we don’t have evidence for them, how do we know there are more powerful lifespan extension molecules than rapamycin?
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Exactly… you’re fairly young… body not crapped out from bad habits and bad food, so a lower dose might be more appropriate.
My 6 mg weekly past 5 years has been excellent for 60 years up dosing.
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See prompt here: Using AI for Health and Longevity and Research - Your Favorite Prompts - #162 by RapAdmin
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I said it is likely. I think GLP1RA’s could easily outperform rapamycin in terms of life extension if they were tested head to head.
If we merely look at all of the individual possible health benefits given by rapamycin vs GLP1RAs I believe there are more benefits from GLP1RA’s.
That’s just looking at things currently approved, there are many new things being developed and studied right now.
The odds that one of them isn’t more powerful than rapamycin is low.
Rapamycin Longevity Lab discovered multiple mTOR modulating compounds that extended C elegans lifespan more than rapamycin.
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I would say it’s possible that some of the GLP1s could provide better life extension than rapamycin. Certainly there is a lot more money being poured into clinical trials of GLP1s than there ever will be for rapamycin as rapamycin is off-patent (so even if rapamycin outperforms, or can outperform GLP1s the data is likely to be more voluminous than for rapa).
And yes, there may be other MTOR inhibitors that are better than rapamycin out there, but its going to take 20 to 30 years to build up the same level of clinical research data that we have on rapamycin, so don’t hold your breath on those being helpful and practically usable anytime soon.
And, it doesn’t really matter if a GLP1 is better than rapamycin, because they are largely complimentary drugs, so people can easily take both. From Claude Opus 4.8:
GLP-1 agonists and rapamycin are predominantly complementary, not contraindicated
On current evidence, GLP-1 agonists and rapamycin are predominantly complementary, not contraindicated — but they share one real overlapping liability (muscle/lean-mass loss) that has to be actively managed. There is no known pharmacokinetic drug–drug interaction; the interaction is physiological and mostly favorable. The field’s own confidence in complementarity is signaled by the ARPA-H–funded VITAL-H trial (UT Health San Antonio, ~$38M, 2026), which puts semaglutide, rapamycin, and dapagliflozin head-to-head against placebo for healthspan.
Where they complement each other
The strongest argument for pairing is that **GLP-1 agonists directly offset rapamycin’s principal metabolic downside.**Rapamycin’s main liability at longevity-relevant exposures is glucose intolerance and insulin resistance, driven not by its intended mTORC1 inhibition but by off-target mTORC2 disruption (loss of insulin-mediated suppression of hepatic gluconeogenesis). Critically, this metabolic penalty is uncoupled from the longevity benefit — mice with genetically reduced mTORC1 live longer with normal glucose handling. So the insulin resistance is a side effect you’d like to erase without losing the lifespan effect. GLP-1 agonists do essentially the opposite thing metabolically: they enhance glucose-dependent insulin secretion and improve insulin sensitivity. Mechanistically that makes GLP-1 a rational “buffer” against rapamycin-induced glucose intolerance, which is most problematic in people who are already insulin-resistant or prediabetic.
Beyond glucose, the two hit different but converging aging pathways. Rapamycin’s core action is autophagy induction via mTORC1 inhibition. GLP-1 agonists act largely upstream/orthogonally — appetite and weight reduction, reduced systemic inflammation, senescence and epigenetic-aging effects (semaglutide slowed multiple DNA-methylation clocks in an RCT), and a ~20% reduction in major cardiovascular events (SELECT) that appears partly independent of weight loss. Interestingly, some of GLP-1’s benefit is itself described as mTORC1 modulation of inflammatory signaling, so there’s mechanistic rhyme rather than conflict. Non-overlapping mechanisms with a shared endpoint (reduced inflammaging, improved metabolic and cardiovascular aging) is the textbook profile for a complementary combination.
How that shapes practical use
The pairing looks most favorable, and most like a true synergy, in metabolically unhealthy / overweight individuals: GLP-1 handles adiposity and neutralizes rapamycin’s glucose penalty. It warrants more caution in lean, older, or already-sarcopenic individuals, where combined lean-mass loss is the dominant risk. Standard mitigations map directly onto the mechanism: weekly (not daily) rapamycin dosing to spare mTORC2 and preserve anabolic windows, robust resistance training, high protein intake (timed away from the rapamycin dose so acute MPS isn’t blunted), and monitoring of body composition (DEXA), fasting glucose/HbA1c, and lipids. Minor additive tolerability issues also exist — GI effects from GLP-1 plus rapamycin’s mucosal/immune effects — but these are nuisance-level, not safety-defining.
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It’s also not really fair to compare rapamycin, a single mTOR inhibitor, to an entire class of existing, in trial and future created GLP1RA drugs. But I still stand by my prediction.
I take both.
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GLP-1 agonists also activate AMPK which causes downstream inhibition of mTORC1. So there could potentially be some additive effect when GLP-1 is added to a rapamycin protocol
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I have been taking Rapa 6 mg weekly for 5 years now. I am 71, leaner, and have more muscle than I ever have. For the last 3 years, I have been sick (mild flu/cold) once a year, compared to 2 to 3 times a year, with sometimes much more serious symptoms before Rapa.
Is it all because of Rapa? I don’t know, but the data is compelling, and I am very optimistic and hopeful that Rapa could improve the lives of our aging population.
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That mirrors my experiences, also 5 years of use. Rapamycin is amazing!
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Old guys RULE! Gotta keep the machine moving:) The more you move, the longer you last.
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I skimmed through the presentation and Matt Kaeberlein was really mogging throughout.
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I just got a prescription for Zepbound. Can you comment on how much and when you take rapamycin and your GLP-1? Thanks.
Tirz thurs, rap sat. Doses vary. Start low and slowly increase.
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Peter Attia resurfaced. He does not look that great for a 53 yr old obsessive longevity practitioner.
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You’d probably be able to tell more about his health from his Cbc or CMP than a random photo.
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Why are you posting this in this thread?
Probably because Attia has been a big proponent of rapamycin for many years…
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