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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Youâd 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 yearsâŚ
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Part of that but also part of that Attia is said to have stopped taking Rapamycin about a yr ago if not longer. I thought he looked better back then.
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Photos need to be taken under controlled circumstances if you want to obtain useful information.
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As another data point, I take rapamycin the day before a GLP-1. I worry about the slowed gastric emptying affecting how the rapa works. The day before the next GLP-1 dose seems like the time gastric emptying is back to baseline, so I take my rapa then. I have not noticed the rapa interacting with the GLP-1. I was on the GLP-1 for about a year before starting rapa.
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At what doses?
Why Rapamycin likely has no effect or only a minor effect on human longevity:
- Mainly proven in lower-order species: It is an intervention with robust life-extending effects primarily in lower-order (less complex) species.
- Lack of Mendelian randomization evidence: In humans, one would expect Mendelian randomization to show that mTOR-inhibiting mutations are life-extending. However, there is no such evidence, making me think it doesnât exist. In contrast, there is strong genetic evidence that LDL-suppressive genes reduce lifetime heart disease risk and extend human lifespan.
- Lack of observational evidence: In human cohorts utilizing rapamycin, the therapy isnât associated with longevity or rejuvenation. Even metformin and several other antidiabetic drugs are associated with life extension in their respective patient cohorts. The fact that no analogous evidence exists for rapamycin makes its efficacy highly dubious.
How can humanity make progress here?
- Focus on genes that have a direct causal effect on human lifespan based on Mendelian randomization studies. We will never run a 30-year RCT (and even if we did, it would be too late for current middle-aged people). The closest thing to a 30-year RCT is Mendelian randomization. We must double down on it to find genes that truly make a difference, and then find a way to test them indirectly (via observational studies) or directly (via interventions).
The key to solving this conundrum is to focus on humans; please do not get fooled by mice studies. Less than 5â10% of drugs that work in mice ever get approved for human use.
We both take a GLP1 every day, Rapa once a week, 6 mg my husband and 3 mg me, have done this Rapa regime for several years, husband does 3 months on and one month off, I keep mine going . We are in our 80s and feel much younger. No colds or flue for at least 15 years . We golf 3 times a week, eat only organic , wild Alaska salmon, grass fed meat and eggs etc we have our own gym, a PEMF mat, we do 35 grams Vitimin C IV monthly and have ozone insufflation 3 or 4 times a month . Our little dog has half a gram of Rapa a week also for the last 2 years and her labs are perfect other than she has always had a heart murmur
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I think the LLM summary here is wrong, itâs underplaying the data we have on higher order animals. The marmoset study is probably the most powerful indicator that weâll see good results in humans⌠we are very close to marmosets in many ways (weâre both primates after all). Iâve been speaking with Adam Salmon, the researcher who is running this study at UT southwestern, and heâll have more details later this summer it seems. So weâll have even more data soon.
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I think marmosets study would be great to see. As itâs yet unpublished, itâs hard to make claims.
Btw what I wrote was purely my opinion (written in the style of LLM). It wasnât an LLMâs opinion or data.
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Since, almost universally across species from worms to primates, rapamycin provided life extension results, it is one of the few, if not the only, interventions that I am not skeptical of. What is still up for debate is optimal dosing and timing.
On the N=1 side, I have been taking high-dose rapamycin for over 5 years and have received many health benefits. Life extension remains to be seen.
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not really LOL. Youâre well into your 80âs and were supposed to be dead at 78, so Iâd say youâve already got some life extension benefit. To be fair Iâd like to see someone in their 90âs and using Rapa to be sure of the life extension benefit.
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7.5-10mg tirz. 3-6mg rapa.
I do more or less depending on goals.
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re: Rapamycin or other drugs to extend human lifespan. One point that differs from humans vs dogs, cats, monkeys, mice, worms, etc. is that humans have already drastically improved their lifespan over the past 100 years or so. If we hadnât done it via vaccinations, food supply, infant mortality, etc. then maybe Rapa and others would show similar results as other animals.
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Youâre mixing up two different concepts. One of disease or illness and death prevention (e.g. better prenatal care, vaccines, better food, etc. - you might call this "extrinsic mortality), compared with the basic biology of aging (or âintrinsic agingâ).
A simple example is if you take a mouse out of the wild and put in him a lab environment youâve probably doubled his expected lifespan compared to the wild type (because he no longer is likely to be eaten by predators), but his intrinsic aging rate hasnât changed.
People have always had a max lifespan of around 120 years and people lived until 80 or 90 quite frequently in centuries before. Similarly, mice, monkeys, etc. have a natural limit on their age. What rapamycin and other longevity drugs seem to be doing (and what the researchers are focused on) is slowing the intrinsic aging of the animal or human.
Rapamycinâs demonstrated effect in animals is specifically on intrinsic aging / maximum lifespan , the one thing a century of vaccines and sanitation did not change. So rather than making rapamycin redundant, the current human situation (and medical therapies) leaves that mechanism largely untouched.
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