In this video, we discuss: 0:01:00-David & Matt’s expertise in mTOR & rapamycin 0:12:00-The discovery of rapamycin & first use in humans as an immunosuppressant 0:19:05-Emergence of rapamycin as a molecule with the potential to prolong lifespan 0:25:53-Groundbreaking rapamycin study on mouse lifespan extension & the open questions about the timing & frequency of dosing 0:36:26-Explaining mTOR & the biology behind rapamycin’s effects 0:47:13-Differences in how rapamycin inhibits mTOR complex 1 (MTORC1) versus mTOR complex 2 (MTORC2) 0:51:20-Reconciling the biochemical mechanism of rapamycin with its longevity benefit 0:56:42-Important discoveries about the interplay of amino acids (leucine in particular) & mTOR 1:04:43-Reconciling rapamycin-mediated mTOR inhibition with mTOR's significance in building & maintaining muscle 1:12:00-Unanswered questions around the tissue specificity of rapamycin 1:18:09-Rapamycin’s ability to cross the blood-brain barrier & its potential impacts on brain health & neurodegeneration 1:26:40-Rapamycin may act as an immune modulator in addition to immunosuppressive effects 1:40:41-Might rapamycin induce changes in T cell methylation patterns, potentially reversing biological aging? 1:49:00-Rapamycin side effects & impacts on mental health: fascinating results of Matt’s survey on off-label rapamycin use 1:59:32-Impact of taking rapamycin in people who contracted COVID-19: more insights from Matt’s survey 2:05:20-What David would like to study with mTOR inhibitors 2:09:50-Joan Mannick’s studies of RTB101 & other ATP-competitive inhibitors of mTOR 2:20:10-Impact of mTOR inhibition on autophagy & inflammation & a discussion of biomarkers 2:28:24-The Dog Aging Project: what we’ve learned from testing rapamycin in dogs 2:36:20-Preliminary results of primate studies with rapamycin 2:39:31-Dosing of rapamycin 2:49:33-Effect of rapamycin on fertility 2:55:30-Outlook for future research of rapamycin & the development of rapalogs
Rapamycin is a potent and selective inhibitor of the mechanistic target of rapamycin (mTOR) protein kinase, which acts as a central integrator of nutrient signaling pathways. mTor is a key regulator in maintaining skeletal muscle mass. Rapamycin is an inhibitor of mTOR and mTOR is critical to signaling muscle protein synthesis. Why would rapamycin be used as an anti-aging agent that inhibits muscle protein synthesis? Would resistance muscle training to maintain muscle mass be impaired and cause sarcopenis muscle atrophy?
Thank you for the podcast Dr Attia. You are clearly the most ethical Dr on the internet, nowadays when most Doctors online are trying to sell you something. Your position on that matter was very clear, you don't feel comfortable to promote or sell anything as a doctor even if you believe in that product, for the simple reason that it will interfere with your ethical values as a Dr. You took a noble step giving up a lot $$ where the majority of doctors including your colleagues fail. This indicates your ethics as a doctor but first and foremost as person. Respect for that!
This comment is hilarious if you know how much it costs to be one of his patients (100k+), have him speak at a conference (200k+) or even to take one of his pre-recorded classes (early medical is $2500). He drives race cars just as a fun hobby. Altruism and nobility to give up cash was not a choice he made except for maybe for a transitional period of his life. Dude is loaded beyond anyone's dreams and doesn't need to sell any products but himself. But he's worked his ass off for it and blazed a new trail and offers much of his content for free and for that we thank him.
@@MichaelMerritt that not as much as sabatini's extremely unethical behavior. you can search sabatini hhmi or whitehead termination, sexual misconduct to learn more. so disappointing for attia to give a platform to sabatini.
My son has been on it (Sirolimus) for 6 years for a genetic immune deficiency thanks to the NIH and it has changed his life! He is now in law school and doing so well - where before his condition was steadily declining and he had lung disease on top of everything else. It has completely reversed his lung disease and put his disease into a remission of sorts. Miracle drug!
65 yr old man here, no major medical problems. I've been taking Rapamycin for almost a year, 1mg a week. I tried 2 mg a wk but I felt it was "too much" for my body. I'm getting it online but I think I need to get it from my doctor, but he won't "just prescribe it." Feeling pretty good with more energy, for about 3 days, no major side effects except minor mouth sores again for about 3 days. I do hydrogen peroxide with my tooth brushing and that helps. Im also interested in some kind of clinical study. Yes, expensive $12.USD a pill online. Great discussion.😮
Peter really reinforced something that I always believed in. I have been exercising religiously since I was a teenager, all strength training and cardio. I am 50 now. I have made a lot of bad choices along the way but the one thing that I never did, was stop training. It made me really excited about all the other pieces of the puzzle. I’m working hard on zone 2 training and loving the progress. 💪🏼
This was awesome! You asked the questions that were on my mind lately. The timing of this is amazing. Keep up the long detailed format... the deeper the better.
Hello and Thank you Doctors. Thus far I cannot get anyone in the Medical field to even acknowledge or discuss Rapamycin with me. It is especially important to me because I am now 68 years old and have been Diagnosed with "Fronto Temperal Dementia" as well. So it is probably readily evident as to why greater knowledge of this Rapamycin would be of import to me. So, I basically have been given an "Expiration Date" of sorts. Whenever I speak to my Neurologist, he pats me on the head & sends me home to... Die?! I want to be much more proactive than that and it appears that this may actually be a promising road to travel, if not for myself, perhaps to help in this research, maybe helping pave the way for others in the future? Thank you for sharing this with us all. God is putting little Gold Stars in your books, up there. (lol) Keep Smiling... Cheers...
I heard a former MD recovered from “chronic fatigue” using rapamycin. I suppose this audience is mostly healthy but if any of you know anything about this or of any others who have recovered from ongoing fatigue using this, would you please comment? Thanks.
Besides the great information, the video format and audio quality are amazing! It’s hard to achieve when everyone is in separate parts of the world but you all did it. Thank you!!
Why doesn't Attia just start crowd funding, or go to his Silicone valley friends? He keeps saying how interesting and important and relatively cheap these studies are. He has a huge platform and is himself a millionaire. DO SOMETHING!
And he and Andrew Huberman said they are politically correct on one TH-cam dialogue so Stanford is quite the woke environment except for the Hoover Institution!😂. Dr Attia changed his mind about Metformin but not Ozempic yet.
Tremendous work. Crucial question: what is the implication of what David is saying about R's side effects (ulceration-sores/epithelium) when it comes to autoimmune disease of the GI tract (IBD). It seems that Rapamycin may be effecting 2 opposite directions re: GI autoimmunity. 1.(beneficial) modulating the immune system. 2 causing epithelial breakdown and some ulceration? Any sense of the effect of this on IBD and what prevails?
Fantastic discussion! Should be required listening for anyone interested in longevity using rapamycin, or who is already taking rapamycin for longevity.
Kudos to Peter for having the "cancelled" David Sabatini on his podcast, who in my view is one of the great scientists on the planet, and who should eventually win a Nobel prize, but probably won't. for all the obvious and tiresome reasons.
@yourDoom8 My understanding is that while he was at the Whitehead Institute at MIT, and separated from his wife, he started a relationship with a woman who came to the Institute who was not a direct report but someone who he had "career influence over." The relationship started before she came to Whitehead. The woman eventually brought charges of sexual harassment and Sabatini was obviously going to be kicked out of MIT, so he resigned. Arguably he did violate MIT rules, in that he had a relationship with a fellow MIT citizen. Sabatini was going to move to NYU, but they got cold feet and didn't hire him, sunk ultimately by student protests. While the guy has a couple of start up companies, and apparently some modest funding from Bill Ackman, I think that is it for now. This is the environment we live in. Did he make a policy mistake? Pretty clear he did. Did he engage in harassment? Unclear. In the end, though, none of the actors in this drama will very likely EVER be the significant scientific figure Sabatini is. I daresay this woman got her scalp, and the world of science will no doubt be worse off for it. The cynic in me say brilliance takes a back seat to politically correct woke-ness in today's modern "civilization."
He comes from a family of intellectuals and scientists. It's MIT's loss. I heard Bill Ackman was funding his research and trying to get a new lab off the ground. All the best in this endeavor. Remember guys, all it takes is a crazy vindictive bitch (ex lover) to ruin a person's career.
@yourDoom8Sexual harassment and sexual relationships at work. I wouldn't say he was cancelled. Him resigning was the proper measure. I would never tolerate such conduct in my workplace
Hi Folks, about rapamycin, John Krystal (one of the original Ketamine New Haven group and a co-author on the rapa/ket study) said that because Ketamine activates mTOR, they expected a block of the antidepressant effect. However the result was the opposite of what theoretical knowledge would predict, a potentiated antidepressant effect, and a more enduring one (up to two weeks). So your questions about mechanism are spot on, but this is a great example of why theoretical knowledge of mechanisms does not mean you can predict outcomes, this remains an empirical question. Oh, also, the rapa was administered two hours before the ketamine infusion (two hours to peak blood levels was the thought), and has a much longer half-life, so timing is also an open question requiring empirical answers. So maybe rapa could be administered a day or two before the ketamine administration, or get different outcomes with how this is timed, or maybe even block the rapamycin effects. Very interesting. There is a youtube podcast where Tim Ferriss interviews Krystal about this study.
Can you put this into really, really simple layman’s terms for me? What is the exact relation between Ket/Rapa? Are you saying the Rapamycin can block the effects of Ket? Thanks!
I didn't hear an explicit discussion around the effect of the adaptive immune system vs. the innate immune system. I loved the suggestion to frame the question more broadly: "how is rapamycin improving the immune system?" rather than specifically around methylation. Could it have something to do with how the adaptive immune system works from the top down? (like the thymus being affected?) that'd also be supported by a reduction in inflammation. As the adaptive immune system declines, the innate immune system would have to ramp up, and it just blasts things more indiscriminately with inflammation, right? Could it be that rapamycin modulate adaptive vs innate immune function?
I have been thinking about taking this to help calm down my immune system, I might have RA and am doing well to control whatever the hell is going on by diet, and NMN & resveratrol have helped a lot. I hope that it will just reset or calm down my immune system enough that it causes it to go into remission. The pain in my joints as soon as I eat beef or sugary or refined. I love beef! I am South African and man I miss biltong a lot! If this stuff could help me get to a point where I can eat a tiny bit of bilton, I would be VERY happy! The reason I want to try rapamycin is because I have been given prednisone once before and I had a very bad reaction to it and I had 2 years of heartburn non-stop. It made me feel like I was going to die and so I do not want to take it ever again. If all goes well or even if it fails, I will come back and let you know what my experience is.
What a fascinating podcast as I've been very interested in learning more about Rapamycin. I really need some slides though to make it easier for me to understand the science. 😁
Great episode, thanks. I noted the comment about enteric coated tablets and wondered how the dosage for dogs was being done as these are probably half a tablet. I have been giving 1/4 tablet (0.5mg) to each of my cats once per week and I'm wondering if that is ineffective due to Rapamycin being broken down in the stomach as mentioned around 2:48. Anecdotally we have noticed a huge difference in both cats who are nearing 10 years old - they definitely have more energy and are much more playful so perhaps the effect on mood is a real thing!
I'm surprised there's no mention of Dr Seghal's who used himself as a test subject on the effects of rapamycin and cancer treatment. I think he did some ground breaking work for the field.
Wasn’t one of rapamycin’s early noted actions a very effective treatment for toenail fungus? I know that in the grand scheme, control of toenail fungus is pretty small. However, for sufferers who have not had success with other treatments (Rx or OTC) this is a pretty big deal. Thoughts?
I am surprised that side-effects are not discussed more. In the leaflet of rapamune it is reported that up to 1 out of 10 people (10% of users) get skin cancer! the dosing in the leaflet (for kidney transplantation) is 2 mg per day. from the leaflet it seems that this regimen is usually longer than 3 months, not clear how much longer. So my guess is that a 2 mg/day dose for 3 to 6 months results in the reported risk of skin cancer. quite scary if you ask me
I think this would have benefited from a bit more background on metabolism. Glycolysis vs FAO. Maybe next time you can talk about these topics as well as AMPK and the paradigm of mTOR regulation of T cell metabolic state as canonical example?
mind boggling podcast, always with Attia, I love it, i feel so smart listening to you as I can understand eveything of what is being talked about and I'm very far from the medical field
These two guests need to be introduced to ARROGANTS because they have NONE!!! AND THEY SHOULD!!! The population is so fortunate to have people like this in the world!!!
Organ transplant pharmacist here - sirolimus is still routinely used in several subpopulations for example liver transplant patients with h/o hepatocellular carcinoma and heart transplant patients with cardiac allograft vasculopathy
I'm a liver transplant recepient as of 07/2023. I use Everolimus 2.25 mg twice per day (replaced Cellcept) along with a low dose tacro... I have so many questions which I haven't been able to find answers for (lipids, resistance training etc)
A minor correction for a classic mistake by Peter around the attribution of elevated amyloid in serum or CSF in folks at risk for or already in the Alzheimer's trajectory. This is backwards. They show lowered amyloid in both serum and CSF because of failing clearance. Amyloid PET scans are inversely correlated with beta amyloid in serum and CSF. Part of the overwhelming evidence that autophagy is disturbed in neurodegenerative disorders. And part of the evidence that therefore mtor inhibition may be protective.
OUTSTANDING VIDEO ❤ SO MUCH WE DON'T KNOW AND NOT A BIG CONCERN TO LEARN UNLESS THERE IS GREEDINESS BEHIND IT . I WOULD LOVE TO VOLUNTEER FOR THE TRIALS AS AN ATHLETE . Thank you for bringing great videos and information
I love The Drive but I'm going to skip this one as my FOMO is already too high when it comes to Rapamycin. My Dr says she can't even get access to it in Singapore.😭
Dear Sir, I am 47 years old man, for 12 years I took prednisone and azathioprine because of autoimmune hepatitis. Now for fifteen years I have not taken them because I have achieved remission. My ALT and AST fluctuate between 20 and 30. I would like to take rapamycin for so-called "longevity". Have you had such a clinical case of autoimmune hepatitis and taking rapamycin for longevity?. I do not take any medication, except for vitamin D3. Can I aggravate the disease, or is it possible or regulate my immune system to decrease my ALT and AST below 20 ? Thank you very much in advance. Robert
Bryan Johnson of the popularized blueprint protocol is a good n of 1 study that you can definitely build muscle while on a biweekly 13mg rapamycin protocol and moderate caloric deficit (1:07:35)
As I’m listening to this podcast, I surfed over to Wikipedia to read about rapamycin. I saw references to sex differences in the anti-aging effects of rapamycin use in latter aged female versus male mice and that there seemed to be anti-aging benefits in males, but not in females. Granted, I haven’t surfed over to the 2 references Wikipedia listed for this statement. Still, I think it worthwhile to mention because I want to hear from y’all what your response is.
The references listed: Strong R, Miller RA, Bogue M, Fernandez E, Javors MA, Libert S, et al. (November 2020). "Rapamycin-mediated mouse lifespan extension: Late-life dosage regimes with sex-specific effects". Aging Cell. 19 (11): e13269. doi:10.1111/acel.13269. PMC 7681050. PMID 33145977. "Late-Life Rapamycin Regimens Extend Mouse Lifespan in a Sex-Specific Manner". Nicotinamide Mononucleotide (NMN). 11 November 2020. Archived from the original on 28 February 2021. Retrieved 23 March 2022.
Unfortunately Wikipedia can, now, only be trusted to provide narrative-approved information. ... a sad situation ... But maybe not as damaging as the analogous condition for medical journals .... Etc ....
Actually this type of format, direct - to - the-public presentation by physicians/scientist/researchers 🔬🩻🏊🦮🏎️🧑🔧 (who has been found to be trustworthy) might play a significant part in preserving the usefulness of science and medicine.
@@madison1446 I totally agree! Some of the molecules mentioned seemed to be ditched from further study by pharmaceutical company probably because the patent of one molecule lasted longer than another. When I’m sitting still (instead of running errands), I’ll see if I can listen to time stamped sections to get a bit more specific.
Rapamycin has an effect in both sexes but is a bit larger in the males. Interestingly many interventions work better in males, some equally but I have never seen one that works exclusively in females?
Lysine destroys herpes (mouth, genitals no matter). Arginine feeds it, stay away from foods high in it(chocolate, peanuts, do your research) Take lysine supplements, capsules not tablets, up to 3,000 mg daily.
I had a brain aneurysm bleed, off the circle of Willis , due to a bleed, I was put on a breathing. They but a pin in my head. I am 66. I feel better than I ever did. I had to take anti-rejection drugs,
I have a stupid question but where does the body get all these raw materials such the ribose sugars and dna bases from? All the materials to form proteins for the hundreds of enzymes and other functional proteins that are happening all day long? How much of a meal provides the body with all of these raw materials? Suppose I ate Doritos every day for a month would the body’s processes come to a standstill since I’m not providing protein and the other nutrients?
Considering people have water fasted for 30 days and survived you'd probably just feel like sh*t as your body does what it can with your existing stored nutrients until it runs out of the specific nutrients you need and then your systems start malfunctioning. Then if that went on long enough disease occurs.
Great video and thanks so much for taking the time to go into so much depth on this subject matter. You mentioned reversing ovary atrophying but I’ve not seen any mention of whether Rapamycin helps reverse Thymic involution. I would think this would be of significant interest?
Interesting that Sabbatini doesn't take it. I'm ordering whatever I can find from India based on what you guys are saying, and willing to accept that it might be 20% flour.
@peterattiamd, not to call you out, but why do you keep saying you wish some benevolent billionaire would fund these studies which could be as cheap as $100-200k? Don't you have the money and/or influence to make the cheaper studies happen? I've got to imagine it would not be very hard for you to raise money for a non-profit.
Sadly I don’t think the required clinical trials will ever take place in our nation since there just isn’t enough of an incentive for anyone to fund them. Hopefully some group in China, India or Japan can conduct the trial and we can finally see if it helps humans
New member and subscriber here. Great topic but too little in the clinical benefits, known or speculated, and too much on the details of lab data on the details of mechanism.
![PASULOL รามเกียรติ์ ตอนที่ 4 นนทกพบรัก [Ramakien Ep.4: Nonthok in love]](http://i.ytimg.com/vi/tMUQgmZzf_A/mqdefault.jpg)
In this video, we discuss:
0:01:00-David & Matt’s expertise in mTOR & rapamycin
0:12:00-The discovery of rapamycin & first use in humans as an immunosuppressant
0:19:05-Emergence of rapamycin as a molecule with the potential to prolong lifespan
0:25:53-Groundbreaking rapamycin study on mouse lifespan extension & the open questions about the timing & frequency of dosing
0:36:26-Explaining mTOR & the biology behind rapamycin’s effects
0:47:13-Differences in how rapamycin inhibits mTOR complex 1 (MTORC1) versus mTOR complex 2 (MTORC2)
0:51:20-Reconciling the biochemical mechanism of rapamycin with its longevity benefit
0:56:42-Important discoveries about the interplay of amino acids (leucine in particular) & mTOR
1:04:43-Reconciling rapamycin-mediated mTOR inhibition with mTOR's significance in building & maintaining muscle
1:12:00-Unanswered questions around the tissue specificity of rapamycin
1:18:09-Rapamycin’s ability to cross the blood-brain barrier & its potential impacts on brain health & neurodegeneration
1:26:40-Rapamycin may act as an immune modulator in addition to immunosuppressive effects
1:40:41-Might rapamycin induce changes in T cell methylation patterns, potentially reversing biological aging?
1:49:00-Rapamycin side effects & impacts on mental health: fascinating results of Matt’s survey on off-label rapamycin use
1:59:32-Impact of taking rapamycin in people who contracted COVID-19: more insights from Matt’s survey
2:05:20-What David would like to study with mTOR inhibitors
2:09:50-Joan Mannick’s studies of RTB101 & other ATP-competitive inhibitors of mTOR
2:20:10-Impact of mTOR inhibition on autophagy & inflammation & a discussion of biomarkers
2:28:24-The Dog Aging Project: what we’ve learned from testing rapamycin in dogs
2:36:20-Preliminary results of primate studies with rapamycin
2:39:31-Dosing of rapamycin
2:49:33-Effect of rapamycin on fertility
2:55:30-Outlook for future research of rapamycin & the development of rapalogs
Much respect to Dr Attia for personally donating and calling on your friends to contribute to the Dog Aging Project's rapamycin study.
Does Peter Atila take rapamycin?
Rapamycin is a potent and selective inhibitor of the mechanistic target of rapamycin (mTOR) protein kinase, which acts as a central integrator of nutrient signaling pathways.
mTor is a key regulator in maintaining skeletal muscle mass.
Rapamycin is an inhibitor of mTOR and mTOR is critical to signaling muscle protein synthesis.
Why would rapamycin be used as an anti-aging agent that inhibits muscle protein synthesis?
Would resistance muscle training to maintain muscle mass be impaired and cause sarcopenis muscle atrophy?
so disappointed to see you have given a platform to sabatini. he does not deserve a platform. his ethical transgressions are now on you too.
He does, or did!@@susymay7831
Thank you for the podcast Dr Attia.
You are clearly the most ethical Dr on the internet, nowadays when most Doctors online are trying to sell you something. Your position on that matter was very clear, you don't feel comfortable to promote or sell anything as a doctor even if you believe in that product, for the simple reason that it will interfere with your ethical values as a Dr.
You took a noble step giving up a lot $$ where the majority of doctors including your colleagues fail.
This indicates your ethics as a doctor but first and foremost as person. Respect for that!
This comment is hilarious if you know how much it costs to be one of his patients (100k+), have him speak at a conference (200k+) or even to take one of his pre-recorded classes (early medical is $2500). He drives race cars just as a fun hobby. Altruism and nobility to give up cash was not a choice he made except for maybe for a transitional period of his life. Dude is loaded beyond anyone's dreams and doesn't need to sell any products but himself. But he's worked his ass off for it and blazed a new trail and offers much of his content for free and for that we thank him.
@@MichaelMerritt that not as much as sabatini's extremely unethical behavior. you can search sabatini hhmi or whitehead termination, sexual misconduct to learn more. so disappointing for attia to give a platform to sabatini.
My son has been on it (Sirolimus) for 6 years for a genetic immune deficiency thanks to the NIH and it has changed his life! He is now in law school and doing so well - where before his condition was steadily declining and he had lung disease on top of everything else. It has completely reversed his lung disease and put his disease into a remission of sorts. Miracle drug!
What dose is he taking?
10mg per day for last 6 years - it's completely reversed his GLILD@@nerin3624
@@nerin3624 If it's for cancer, probably...high.
65 yr old man here, no major medical problems. I've been taking Rapamycin for almost a year, 1mg a week. I tried 2 mg a wk but I felt it was "too much" for my body. I'm getting it online but I think I need to get it from my doctor, but he won't "just prescribe it." Feeling pretty good with more energy, for about 3 days, no major side effects except minor mouth sores again for about 3 days. I do hydrogen peroxide with my tooth brushing and that helps. Im also interested in some kind of clinical study. Yes, expensive $12.USD a pill online. Great discussion.😮
Where do u get rapamycin from??
I've applied to AgelessRX online. $95 per month. One of Dr. Kaeberlein's collaborators is involved in the company.
Peter really reinforced something that I always believed in. I have been exercising religiously since I was a teenager, all strength training and cardio. I am 50 now. I have made a lot of bad choices along the way but the one thing that I never did, was stop training.
It made me really excited about all the other pieces of the puzzle. I’m working hard on zone 2 training and loving the progress. 💪🏼
Good exercises work even starting in 60s tho start earlier may have certain degree of additional benefits.
The discussion on dosing is sobering concerning the current human dosages in longevity circles.
2:39:31-Dosing of rapamycin
Hands down the best panel of experts.
Hope that as many people as possible would hear this quality discussion.
This was awesome! You asked the questions that were on my mind lately. The timing of this is amazing. Keep up the long detailed format... the deeper the better.
@@LisaC_aparentandsuchOPPO?
Hello and Thank you Doctors. Thus far I cannot get anyone in the Medical field to even acknowledge or discuss Rapamycin with me. It is especially important to me because I am now 68 years old and have been Diagnosed with "Fronto Temperal Dementia" as well. So it is probably readily evident as to why greater knowledge of this Rapamycin would be of import to me. So, I basically have been given an "Expiration Date" of sorts. Whenever I speak to my Neurologist, he pats me on the head & sends me home to... Die?! I want to be much more proactive than that and it appears that this may actually be a promising road to travel, if not for myself, perhaps to help in this research, maybe helping pave the way for others in the future? Thank you for sharing this with us all. God is putting little Gold Stars in your books, up there. (lol) Keep Smiling... Cheers...
have you discussed intermittent fasting? have you looked at the literature about SDAT and IF?
You can get it online right now... Just look up rapamycin for sale.
I heard a former MD recovered from “chronic fatigue” using rapamycin. I suppose this audience is mostly healthy but if any of you know anything about this or of any others who have recovered from ongoing fatigue using this, would you please comment? Thanks.
The best 3hrs I've ever spent on a podcast - very balanced, very insightful
Besides the great information, the video format and audio quality are amazing! It’s hard to achieve when everyone is in separate parts of the world but you all did it. Thank you!!
Why doesn't Attia just start crowd funding, or go to his Silicone valley friends? He keeps saying how interesting and important and relatively cheap these studies are. He has a huge platform and is himself a millionaire. DO SOMETHING!
And he and Andrew Huberman said they are politically correct on one TH-cam dialogue so Stanford is quite the woke environment except for the Hoover Institution!😂.
Dr Attia changed his mind about Metformin but not Ozempic yet.
@@Geezerelliwhat did he say about. Metformin?
Tremendous work. Crucial question: what is the implication of what David is saying about R's side effects (ulceration-sores/epithelium) when it comes to autoimmune disease of the GI tract (IBD). It seems that Rapamycin may be effecting 2 opposite directions re: GI autoimmunity. 1.(beneficial) modulating the immune system. 2 causing epithelial breakdown and some ulceration? Any sense of the effect of this on IBD and what prevails?
Fantastic discussion! Should be required listening for anyone interested in longevity using rapamycin, or who is already taking rapamycin for longevity.
Kudos to Peter for having the "cancelled" David Sabatini on his podcast, who in my view is one of the great scientists on the planet, and who should eventually win a Nobel prize, but probably won't. for all the obvious and tiresome reasons.
@yourDoom8 My understanding is that while he was at the Whitehead Institute at MIT, and separated from his wife, he started a relationship with a woman who came to the Institute who was not a direct report but someone who he had "career influence over." The relationship started before she came to Whitehead. The woman eventually brought charges of sexual harassment and Sabatini was obviously going to be kicked out of MIT, so he resigned.
Arguably he did violate MIT rules, in that he had a relationship with a fellow MIT citizen.
Sabatini was going to move to NYU, but they got cold feet and didn't hire him, sunk ultimately by student protests.
While the guy has a couple of start up companies, and apparently some modest funding from Bill Ackman, I think that is it for now.
This is the environment we live in. Did he make a policy mistake? Pretty clear he did. Did he engage in harassment? Unclear.
In the end, though, none of the actors in this drama will very likely EVER be the significant scientific figure Sabatini is. I daresay this woman got her scalp, and the world of science will no doubt be worse off for it. The cynic in me say brilliance takes a back seat to politically correct woke-ness in today's modern "civilization."
@yourDoom8Sexual harassment I believe
He comes from a family of intellectuals and scientists. It's MIT's loss. I heard Bill Ackman was funding his research and trying to get a new lab off the ground. All the best in this endeavor. Remember guys, all it takes is a crazy vindictive bitch (ex lover) to ruin a person's career.
@yourDoom8Sexual harassment and sexual relationships at work. I wouldn't say he was cancelled. Him resigning was the proper measure. I would never tolerate such conduct in my workplace
@yourDoom8⁸.😅😅😅😅😅😊😅😅😅😅😊😅😅7uu.um.mm
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Wow this podcast is amazing. Thank you for inviting Dr. Sabatini. Hes truely deserving the nobel prize.
How come no one ever mentions David Sinclair, Ph.D.
Hi Folks, about rapamycin, John Krystal (one of the original Ketamine New Haven group and a co-author on the rapa/ket study) said that because Ketamine activates mTOR, they expected a block of the antidepressant effect. However the result was the opposite of what theoretical knowledge would predict, a potentiated antidepressant effect, and a more enduring one (up to two weeks). So your questions about mechanism are spot on, but this is a great example of why theoretical knowledge of mechanisms does not mean you can predict outcomes, this remains an empirical question. Oh, also, the rapa was administered two hours before the ketamine infusion (two hours to peak blood levels was the thought), and has a much longer half-life, so timing is also an open question requiring empirical answers. So maybe rapa could be administered a day or two before the ketamine administration, or get different outcomes with how this is timed, or maybe even block the rapamycin effects. Very interesting. There is a youtube podcast where Tim Ferriss interviews Krystal about this study.
Can you put this into really, really simple layman’s terms for me? What is the exact relation between Ket/Rapa? Are you saying the Rapamycin can block the effects of Ket? Thanks!
I didn't hear an explicit discussion around the effect of the adaptive immune system vs. the innate immune system. I loved the suggestion to frame the question more broadly: "how is rapamycin improving the immune system?" rather than specifically around methylation. Could it have something to do with how the adaptive immune system works from the top down? (like the thymus being affected?) that'd also be supported by a reduction in inflammation. As the adaptive immune system declines, the innate immune system would have to ramp up, and it just blasts things more indiscriminately with inflammation, right? Could it be that rapamycin modulate adaptive vs innate immune function?
I have been thinking about taking this to help calm down my immune system, I might have RA and am doing well to control whatever the hell is going on by diet, and NMN & resveratrol have helped a lot. I hope that it will just reset or calm down my immune system enough that it causes it to go into remission. The pain in my joints as soon as I eat beef or sugary or refined. I love beef! I am South African and man I miss biltong a lot! If this stuff could help me get to a point where I can eat a tiny bit of bilton, I would be VERY happy! The reason I want to try rapamycin is because I have been given prednisone once before and I had a very bad reaction to it and I had 2 years of heartburn non-stop. It made me feel like I was going to die and so I do not want to take it ever again. If all goes well or even if it fails, I will come back and let you know what my experience is.
Rule out that you don't have gout.
You should try it! It's been around long enough. AgelessRX offers it in the US.
Veterinary professional here. You have my attention on 2 levels
... great, and...
What a fascinating podcast as I've been very interested in learning more about Rapamycin. I really need some slides though to make it easier for me to understand the science. 😁
Great episode, thanks. I noted the comment about enteric coated tablets and wondered how the dosage for dogs was being done as these are probably half a tablet. I have been giving 1/4 tablet (0.5mg) to each of my cats once per week and I'm wondering if that is ineffective due to Rapamycin being broken down in the stomach as mentioned around 2:48. Anecdotally we have noticed a huge difference in both cats who are nearing 10 years old - they definitely have more energy and are much more playful so perhaps the effect on mood is a real thing!
I'm surprised there's no mention of Dr Seghal's who used himself as a test subject on the effects of rapamycin and cancer treatment. I think he did some ground breaking work for the field.
What about sarcopenia and muscle health in older dogs on rapamycin?
Ty Peter for covering Longevity ❤
Wasn’t one of rapamycin’s early noted actions a very effective treatment for toenail fungus? I know that in the grand scheme, control of toenail fungus is pretty small. However, for sufferers who have not had success with other treatments (Rx or OTC) this is a pretty big deal. Thoughts?
worked for me. Google it and you'll see it seems to work well as a topical solution too (I take orally)
Yes I believe that’s how rapamycin was first used
P.S. Thank you for doing this show and thank you for the information! You are the best!
I am surprised that side-effects are not discussed more. In the leaflet of rapamune it is reported that up to 1 out of 10 people (10% of users) get skin cancer! the dosing in the leaflet (for kidney transplantation) is 2 mg per day. from the leaflet it seems that this regimen is usually longer than 3 months, not clear how much longer. So my guess is that a 2 mg/day dose for 3 to 6 months results in the reported risk of skin cancer. quite scary if you ask me
Use your platform to get these studies done please!
I think this would have benefited from a bit more background on metabolism. Glycolysis vs FAO. Maybe next time you can talk about these topics as well as AMPK and the paradigm of mTOR regulation of T cell metabolic state as canonical example?
mind boggling podcast, always with Attia, I love it, i feel so smart listening to you as I can understand eveything of what is being talked about and I'm very far from the medical field
You mentioned L-Arginine. what role does that play?
similar to leucine?
These two guests need to be introduced to ARROGANTS because they have NONE!!! AND THEY SHOULD!!! The population is so fortunate to have people like this in the world!!!
Organ transplant pharmacist here - sirolimus is still routinely used in several subpopulations for example liver transplant patients with h/o hepatocellular carcinoma and heart transplant patients with cardiac allograft vasculopathy
I'm a liver transplant recepient as of 07/2023. I use Everolimus 2.25 mg twice per day (replaced Cellcept) along with a low dose tacro... I have so many questions which I haven't been able to find answers for (lipids, resistance training etc)
Thank you, dr. Attia. You are great.
A minor correction for a classic mistake by Peter around the attribution of elevated amyloid in serum or CSF in folks at risk for or already in the Alzheimer's trajectory. This is backwards. They show lowered amyloid in both serum and CSF because of failing clearance. Amyloid PET scans are inversely correlated with beta amyloid in serum and CSF. Part of the overwhelming evidence that autophagy is disturbed in neurodegenerative disorders. And part of the evidence that therefore mtor inhibition may be protective.
This is a very excellent podcast. Thank you so much.
OUTSTANDING VIDEO ❤ SO MUCH WE DON'T KNOW AND NOT A BIG CONCERN TO LEARN UNLESS THERE IS GREEDINESS BEHIND IT . I WOULD LOVE TO VOLUNTEER FOR THE TRIALS AS AN ATHLETE . Thank you for bringing great videos and information
I love The Drive but I'm going to skip this one as my FOMO is already too high when it comes to Rapamycin. My Dr says she can't even get access to it in Singapore.😭
Does taking Lysine help prevent the cold sores? and would that impact the effects of rapa in some way?
It is not cold sores(which are due to Herpes Simplex virus) that can be aided by Lysine, it is non-viral mouth ulcers.
Sirolimus cost less than 2.00 mg at Mark Cuban Cost Plus
Is it an FDA approved generic for Rapamycin?
Yes, and less than $1.00 per 1 mg tablet from many good online Indian pharmacies.
Dear Sir, I am 47 years old man, for 12 years I took prednisone and azathioprine because of autoimmune hepatitis. Now for fifteen years I have not taken them because I have achieved remission. My ALT and AST fluctuate between 20 and 30. I would like to take rapamycin for so-called "longevity". Have you had such a clinical case of autoimmune hepatitis and taking rapamycin for longevity?. I do not take any medication, except for vitamin D3. Can I aggravate the disease, or is it possible or regulate my immune system to decrease my ALT and AST below 20 ? Thank you very much in advance.
Robert
Bryan Johnson of the popularized blueprint protocol is a good n of 1 study that you can definitely build muscle while on a biweekly 13mg rapamycin protocol and moderate caloric deficit (1:07:35)
Great video to all 3 of you. 👍👍
Fantastic interview. Thank you
As I’m listening to this podcast, I surfed over to Wikipedia to read about rapamycin. I saw references to sex differences in the anti-aging effects of rapamycin use in latter aged female versus male mice and that there seemed to be anti-aging benefits in males, but not in females.
Granted, I haven’t surfed over to the 2 references Wikipedia listed for this statement.
Still, I think it worthwhile to mention because I want to hear from y’all what your response is.
The references listed:
Strong R, Miller RA, Bogue M, Fernandez E, Javors MA, Libert S, et al. (November 2020). "Rapamycin-mediated mouse lifespan extension: Late-life dosage regimes with sex-specific effects". Aging Cell. 19 (11): e13269. doi:10.1111/acel.13269. PMC 7681050. PMID 33145977.
"Late-Life Rapamycin Regimens Extend Mouse Lifespan in a Sex-Specific Manner". Nicotinamide Mononucleotide (NMN). 11 November 2020. Archived from the original on 28 February 2021. Retrieved 23 March 2022.
Unfortunately Wikipedia can, now, only be trusted to provide narrative-approved information. ... a sad situation ... But maybe not as damaging as the analogous condition for medical journals .... Etc ....
Actually this type of format, direct - to - the-public presentation by physicians/scientist/researchers 🔬🩻🏊🦮🏎️🧑🔧 (who has been found to be trustworthy) might play a significant part in preserving the usefulness of science and medicine.
@@madison1446 I totally agree!
Some of the molecules mentioned seemed to be ditched from further study by pharmaceutical company probably because the patent of one molecule lasted longer than another.
When I’m sitting still (instead of running errands), I’ll see if I can listen to time stamped sections to get a bit more specific.
Rapamycin has an effect in both sexes but is a bit larger in the males.
Interestingly many interventions work better in males, some equally but I have never seen one that works exclusively in females?
Can you make an episode about kids with autism?
Everything from food, behaveral tools, sauna, supplements and more?
Mouth Sores: you had mentioned Arginine earlier; a higher Arginine:Lysine ratio might encourage some mouth virus sores😊
Lysine destroys herpes (mouth, genitals no matter). Arginine feeds it, stay away from foods high in it(chocolate, peanuts, do your research) Take lysine supplements, capsules not tablets, up to 3,000 mg daily.
Or a xylitol mint or disc as per DDS DrEllie.
I had a brain aneurysm bleed, off the circle of Willis , due to a bleed, I was put on a breathing. They but a pin in my head. I am 66. I feel better than I ever did. I had to take anti-rejection drugs,
Heck yes. So excited. Thanks so much!
The marmoset trial published no effect on epigenome. "DNA methylation age analysis of rapamycin in common marmosets".
I have a stupid question but where does the body get all these raw materials such the ribose sugars and dna bases from? All the materials to form proteins for the hundreds of enzymes and other functional proteins that are happening all day long? How much of a meal provides the body with all of these raw materials? Suppose I ate Doritos every day for a month would the body’s processes come to a standstill since I’m not providing protein and the other nutrients?
Considering people have water fasted for 30 days and survived you'd probably just feel like sh*t as your body does what it can with your existing stored nutrients until it runs out of the specific nutrients you need and then your systems start malfunctioning. Then if that went on long enough disease occurs.
Great video and thanks so much for taking the time to go into so much depth on this subject matter. You mentioned reversing ovary atrophying but I’ve not seen any mention of whether Rapamycin helps reverse Thymic involution. I would think this would be of significant interest?
Is a low-protein diet the best way to reduce mTOR activation?
I'm very interested in seeing how Rapa helps osteoarthritis.
Most critical, Attia: "We shouldn't think of this as an immune suppressant, we should think of this as an immune modulator."
David's house analog makes lots of sense which directly points to the direction of manipulating the power plant, mitochondria.
Interesting that Sabbatini doesn't take it. I'm ordering whatever I can find from India based on what you guys are saying, and willing to accept that it might be 20% flour.
Thank you! Thank you! Thank you!😊
Amazing discussion. Thank you for sharing
Nice t- shirt
I was waiting for this episode ❤
this is such an interesting conversation?
Does lonafarnib has an impact on general ageing?
Always smart, useful, and mind blowing too.
Fascinating. Thanks Docs.
i did some research on rapamycin and came across a study showing decrease in size of the testicals....... Any feedback on that research?
So I'll be able to buy some Rapamycin when?
Now. Google it - lots of sources.
Muy buena discusión! Muchas Gracias !!!
@peterattiamd, not to call you out, but why do you keep saying you wish some benevolent billionaire would fund these studies which could be as cheap as $100-200k? Don't you have the money and/or influence to make the cheaper studies happen? I've got to imagine it would not be very hard for you to raise money for a non-profit.
It's pretty crass to think benevolent billionaires should just fund this clowns research. Fund it yourself. What a barnacle or is it a leach?
my favorite topic :)
Sadly I don’t think the required clinical trials will ever take place in our nation since there just isn’t enough of an incentive for anyone to fund them. Hopefully some group in China, India or Japan can conduct the trial and we can finally see if it helps humans
Not a word on prolonged fasting with regards to mTor?
Thank you 🙏
How can we get Rapamycin
Online it's for sale just look it up. About 100 for a month supply
My observational ‘study’ indicates that rapamycin creates long-windedness and reiterations. Please provide some synthetic comments.
could the mouth (GI?) sores be remediated by Ozone tx?
Just cut back the dose
You would imagine that all three of these guys would be taking Rapamycin themselves, no?
Skin and hair turn over fast but it benefits them correct? How fast is spermatogenesis compared to hair nails?
Ought to culture people for candida and see if that explains the mouth sores.
Incredible interview, thank you!
New member and subscriber here. Great topic but too little in the clinical benefits, known or speculated, and too much on the details of lab data on the details of mechanism.
The benefits are well known, 15% to 30% lifespan improvement in dozens of mammal/rodent studies.
Does Peter Atila take rapamycin?
So just how long do the animals on Easter Island live are they out living other comparable animals from other parts of the world?
Need to get it approved for Cowden Syndrome. ATM we have to buy it from India
53:00 hey aslong as it works Indont need to get it😂 like alien tech😎
1:28:00 rapalogs, cheaper derivatives?
Damn my dog is to small! I’m all in on extending her life.
this is at ~1h 6 min time stamp
Taurine?
Nothing is hotter than a three-way!
No tuna for cats
1:56:30 ketamine😱
Running out mice, save and put outside
Makes stones
Whair I get in Nepal nmn sublimen