4:51 "...that paper concludes that exercise doesn't work, healthy diet doesn't work, and rapamycin doesn't work..." Those are not at all the conclusions of our pre-print. The pre-print investigates the responsiveness of epigenetic clocks, and is not really interested in the impact of any single intervention. The fact that many of these healthy life habits, such as diet and exercise, did not show a significant decrease in the epigenetic clock scores says much more about the epigenetic clocks than it does about the interventions themselves. Seems like you and Bryan Johnson entirely missed that point from the paper. It's not about the interventions - it's about the clocks. But thank you for the feedback, we'll need to emphasize this point as we rework it for submission for peer-review. Cheers!
I think you are doing a great job Matt. I really liked the way you explained the actual science, with regards to the studies. I totally agree with everything you said in this podcast. You're genuine, honest and unbiased.
MK and Nick - godsend! Frank, honest, bold, packed full of wisdom to those who will listen and consider. Thank you for giving me ideas to navigate health decisions.
Always appreciate your clear-headed approach, Matt. This comes from and 80yo fan of your podcast, have used rapa for six years, extensive blood tests 4x/year show low lipids, ApoB 60 or lower. I believe that when finally extensive tests have been done about rapa and its side effects that it will have a different effect on different people. But certainly at this point it would be silly to make blanket statements. As always, thanks for your informative discussions.
I've really been enjoying your videos and your objective perspective on all this. There's so much out there on everything longevity related but difficult finding truly impartial voices. Much appreciated!
Hey Matt, stoked to have you covering our work. We would love to hear your thoughts on it more, I think it is tangentially related to your recent experiment with the multiple at-home biological age tests... 15:50 “the signal…isn’t strongly correlated with the things that promote health, so it’s hard to know what it means” It's like you entirely get it one moment, and then entirely miss it the next. Our work was never intended to be interpreted as, "oh this intervention is actually crap, oh this intervention will help me live longer..." Our goal was to check something that no-one had never tested before: are epigenetic clocks responsive. Do they actually respond to anti-aging interventions? I personally was shocked to see that many of the well known clocks (Horvath, Hannum) failed to pick up any change amongst 51 "interventions" (Figure 4B). Likewise, it's quite concerning that so many well known aging interventions, like exercise and diet, do not cause a significant decrease in epigenetic age across many clocks (Figure 3B), despite their documented correlation with lifespan. This is worth shouting about, and should drive further investigation! Nowhere in our paper do we make any conclusions about the impact of a particular intervention on longevity. Rather, that the epigenetic clocks seem to be sensitive to some interventions more than others. Take Figure 3D for example, which makes this point well: the clocks seem more responsive to pharmacological than to lifestyle interventions. In the discussion, we hint that in some cases, this is likely due to a drugs direct effect on a specific biological pathway (as apposed to the systemic impact a lifestyle intervention may have). Heated debate aside, we really appreciate you and the rest of the communities feedback. As we prepare our work for peer review, we will emphasize many of the points I've made here, and hope that will help sharpen our findings for future readers. Ultimately it is on us, the authors, to make our findings clear, and foresee the possible intellectual pitfalls that may arise when reading our work. Cheers!
Do you guys have any input on the new head (pending) of the FDA who is a believer in age-reversal and longevity science and how it will move along the field ??
Matt and I were talking yesterday about doing an episode on a topic similar to this. I’ll look into the new head of the FDA and get Matt’s opinion. Thank you! Nick
I posted 3 weeks ago about stopping rapamycin because my "bioage" got "older" not better with rapamycyn. To keep this simple, I'll show my changes in bioage relative to chrono age as time went on. Right before starting rapamycin my bioage was -11 years ("younger)." After 7 weeks of rapamycin my bioage was again -11, so no change with rapamycin. But then after another 7 weeks, my bioage worsened to -6.5 years. After another 8 weeks on rapamylcyn my bioage worsened more to -6.0. So then I decided to stop taking it and wait another 7-8 weeks are do another blood test. This time my bioage recovered to -8.2. That's not back to my baseline -11 years but seems to be headed in the right direction. Now I know all the caveats about the bioage measures, but that's all I have to go on. You could quiz me about components of my blood work but that's what the bioage measures are based on. So I'm done with rapamycyn. The fact that it is so expensive also made the decision a little easier.
Says he doesn’t know anything about BJ, but still makes a lot of speculation about the validity of any of BJ’s findings. And he doesn’t seem to get the basic point that BJ is using himself as a data point by constantly testing himself to see if his changes are delivering the hypothesised results or not. As with Rapamycin, he’ll take 3 months off, get tested again, and see if the biomarkers changed or not.
Whenever the topic of longevity comes up I’m invariably asked what I think of Bryan Johnson. I always say - Sometimes you can spend so much time and money trying not to die that you forget to live.
9:30: "He mentions resting heart rate decrease..." Actually it appears the tweet mentions resting heart rate *increase." Important difference, as all else being equal a resting a heart rate decrease would be an indicator of increased health, whereas an increase would imply decreased health.
It decreased when he got off of Rapamycin, indicating Rapamycin was somehow increasing his RHR. Which I agree would be a negative effect if true. - Nick
I stopped Rapamycin when my "bioage" got worse relative to my chrono age after taking it. I'm going to retest soon after about 10 weeks abstinence. I'll reconsider when I get the results. Caveat: I know about the limits or even the legitimacy of the various bioage measures.
@MsElaine122 I have. That's why I'm not sure of anything. But none of us are sure of Rapamycin, so maybe I should err on the side of caution. I'm old anyway, so I don't have a lot of longevity potential. I have to take all of this into consideration.
@@bill9989 You could look for improved general health marks, rather then agetest. If more health marks improve then get worse (at least if those getting worse isn't moving into harmful ranges), it probably a net positive
@zombi3lif3 Thanks, but I'm all over my health indicators. Before rapamycin, my bioage was 11 years "younger." After 20 weeks on, my bioage dropped to 6 years "younger." Again, I know these tests aren't validated. But also, my fasting glucose went up a little bit, but my triglycerides went up significantly.
I don't know how much Dr. Oliver Zolman is involved with Bryan Johnson's selections of therapies, but this Doc has made some strange comments in his videos - some of which make one question what kind of doctor he actually is.
It fits perfectly with Johnsons claims of being science based. He pretty much done the same protocol from the start, claiming everything have had to fight for it's place in the protocol. I don't believe he ever taken the time, to test every intervention by itself. It looks more like a forced from day one protocol. Particularly when compared to Michael Lustgarden, from Conquer aging or die trying, who been posting his quest for the perfect protocol, for 3-4 years, and he is still do adjustments to improve his data
I'm curious if taking a very small dose of rapamycin (e.g., 1mg/weekly) with grapefruit juice would be equivalent to a 3-4mg/weekly dose of Rapamycin alone.
Appreciate the video! If we're allowed to pick on one thing, I'd say to refrain from character assassinations. We're here for the scientific takes, not the mud throwing.
@MusixPro4u Not sure why you are here but it is your opinion not everybody elses ie do not speak for others and it seems like the only one attempting "character assassination" and "mud throwing" is you. Also, any opinion using a psedonym (no name) makes it questionable to say the least. I would bet that 99,9% of the viewers and subsribers appreciate the healthy skepticism and the deep dives into (and irony of) what various "influencers" are pushing to people which usually involves some products. There is none of that here and it is so appreciated by myself I absolutely love Matt Kaeberlein and the work he is doing for free on this channel ❤
@@optispan Please continue doing the awesome work you do on this channel including the healthy skepticism ❤ It is very much needed in this day and age where various individuals are pushing products and other stuff (which in my humble opinion automatically discredits them from the very start).
One of the best TH-cam channels for true longevity, information, and science. Well done. Only minor issues with bias or name calling compared to all others.
Thanks for another interesting video. I did find it entertaining. I have followed Bryan Johnson and I tend not to be influenced by him, because I see his journey as a personal experiment that apart from eating healthy and exercise I would be wary on considering the rest
The pre-print data includes a "rapa dose 3" that showed "accelerated" aging. You didn't mention this in your video...I think that's what Bryan was referring to.
I (64) have been taking 5mg Rapamycin once every 6 weeks for 6 years. Although Johnson says (based upon that post, I don't follow him) he tried different doses of R, all those doses were on the high end of the spectrum, very high considering his body weight, for anti-aging, I don't understand why he would not have just changed to an intermittent dosing schedule like mine. Sorry to hear about Dr Green, fwiw when I met with him 6 years ago he was very frail. I am skeptical Johnson had been taking R for 6 years.
I think you definitely have Bryan Johnson on. He says, "You don't have to buy my products; you do you." He might not be deliberately disingenuous, but may have biases influencing his decisions to be a big influencer and merchandiser.
@@optispan That would be great. He spends $2 million a year on research. He promotes for humanity, "Don't die." Can his regimen and products impact the things that contribute to death: telomere shortening, epigenetic drift, mitochondrial decline, and genomic instability? I also think Dr. Mike had a great idea that one person is a single study, but a scientific study of 15 people, would quantify his goals.
Some people should be careful LEARNING POINTS Ketamine use disorder can lead to severe cardiovascular complications, including acute systolic heart failure, likely due to its direct negative inotropic effects and dose-dependent impact on cardiac function. Clinicians should consider screening for ketamine use disorder in young adults presenting with acute systolic heart failure, especially when other common aetiologies have been ruled out. Early recognition and prompt treatment of ketamine-induced heart failure with diuretics and guideline-directed medical therapy can lead to significant improvement in cardiac function, but long-term management should also focus on ensuring cessation of ketamine use disorder.
Guide to popular people in longevity and their positive biases: Charles Brenner - NR Sinclair - Resveratrol Peter Attia - Exercise Kaeberlein (my goat) - Rapamycin One thing I appreciate about people who take their personal longevity to extreme lengths (Bryan Johnson, ConquerAgingOrDieTrying) is that they clearly *really* do not want to die. As far as I can tell, I think they are really trying to find the truth of what will actually make them live longer (rather than defending their status or research or career). Of course, Bryan now has heavy financial incentive to defend the validity of certain things he sells, but in his case I'm not super bothered by that because he's already rich and he comes across as genuine and truth-seeking in his longevity obsession. This is not a knock on Dr. Kaeberlein. I'm only 10min in to the video. I just noticed that the doc is inclined to be more skeptical of Bryan's intentions than I am (maybe rightfully so).
Even if Bryan Johnson lived to be 130, how would we be able to tell which (if any) of his hundreds of different interventions did anything? I don't see at all how what he is doing leads to any useful information. Yes, he may have shown that certain biomarkers change, but the impact of those biomarkers on human healthspan and longevity is still an open question.
@@persistenthomology It's a good point, for sure. But I don't see Bryan's project as a way to increase our knowledge on longevity, but rather as a way to generate interest, hype and investment in longevity research.
I, too, fully appreciate Dr. Kaeberlin, but to be fair, he is always a bit skeptical in his approach. When I disagree with him, I’m forced to defend my own position. He’s more than a valuable asset to this community. As for Stansfield, he tries too hard to be one of the big boys.
Just some off the cuff remarks: BJ has been doing Rapa for 5 years now, so I guess he's been trying different dosages and protocols during that time, while checking what's the impact on his biomarkers. Just guessing here, but I don't think he just stopped because of this study. We don't know yet if there are nefarious motives for BJ actions, but we can't also ignore that Matt has a horse in this race. Anyway as for the study itself, haven't looked into the pre print but still I find it interesting that calorie restriction and exercise don't correlate with longevity (if I got that right about what you were saying). And while it flies in the face of most we know, it still leaves me wondering if there's something here. I've seen my share of centenarians and talked with some of them, and usually there's not a background of athletic pursuits. Sure, most led active lives till they could, but nothing "crazy" like running 4 hours every week. And usually they don't eat that much when older, but don't feel like they are in CR, they just don't expend that much anyway at that age. Sure, they don't overeat and since they are in nursing homes (the ones I have contact with), that means they have regular meals, healthy but also with some desserts thrown in or maybe a cookie before bed. And yes of course, usually medium-short females, not overweight.
Haha you really seem to not like Bryan Johnson. I hope you can meet soon and look into his eyes and then tell us what you think after. I am so torn and I just don't know anymore.
The longer you live the more likely horrific a death will be high. Plus if he lives to 200, how many of those years will he be capable of moving fluidly like he or a younger person can. If he becamebv a quadriplegic or paraplegic or brain damaged at age 120, the next 80 years are gonna be horrible.
There wasn't any saltiness at all, he took great pains to not make it personal and to support Brian's personal decision whilst separating that from the supposed logic behind it. Matt covered both possibilities - that Brian could simply be making a bad decision with bad interpretation of his results, OR that there might be a bad faith marketing component to it. He openly said many times he did not KNOW, but addressed these as possibilities for people to consider. In terms of the available evidence, it would seem to be Brian who has not limited his variables to show that what he is attributing to Rapa is actually attributable to it. So neither of your razors apply.
I quite enjoy your presentations, Matt. IMO, however, they would be considerably improved if you would teach yourself to stop saying "again" over and over. Thx for considering.
Great video and insights on the "blueprint" that Bryan Johnson is promoting! As far as I can see from his case the most visible effects has been from doing various cosmetic procedures (skin, hair) which also inbcludes fat transfers. When it comes to the not dying part I guess time will tell.
Sorry why was he taking rapamycin in the first place? It’s an antibiotic. He was taking an antibiotic for five year’s continuously? What is the science behind that?
It started as something you gave patients when doing organ transplant. But then scientists realized it increased longevity when giving it at low(er) doses, one time a week or something like that. It's an mTOR inhibitor, so that might explain the effect. It also appears to work in all classes of animals that have been studied so far(mice, worms, etc). Lots of YT videos around that explain it better than I can, but that's the gist of it. At this time everyone that is taking it, is doing it on faith so to speak, and mostly because it didn't appear to have any nasty side effects, so why not. The most common are mouth ulcers, which is probably what Bryan is referring to with the "soft tissue infections". Having Bryan stopping this after 5 years, might signal that "something is off" about rapamycin.
Why take for 5 years a drug causing you such side effects? His team 🤔Those side effects he has for years.. yet they only tell him now to stop 🛑 it ? I'm concerned for Bryan Johnson!
they ignored the drop in RHR after dropping rapa. I've feen a follower of the sub for a while and all I see if bad outcomes like increased hba1c in younger participants. My guess it's good to downregulate mtor at a much older age 60+, Bryan is still young enough not to have those issues.
Sounds like the gentleman has a dog in the fight. Why belittle the guy who is reporting why he is no longer taking it. I would have just said " There's no way of him knowing exactly what was causing his side effects or lack of positive effects without having scientifically measured the variables and perhaps not that he is lying.
Why take for 5 years a drug causing you such side effects? His team must be really bad! Those side effects he has for years.. yet they only tell him now to stop 🛑 it ? I'm concerned for Bryan Johnson!
He didn't belittle him at all, he just raised the possibility that an internet personality might not be telling you the unvarnished truth, and might be marketing based on the personality he has invented, which is way more than a slight possibility and the kind of thing way more people need to hear these days. Note that Matt also said that where he stands on it has never been to make positive claims about it, but that there are some positive indications and that the trials need to be done to see what the real deal is. Why are there so many people in this comment section who have such poor comprehension of what was said?
Sorry but I'm gonna put my faith in Bryan who's walking the talk and not you. What credentials do you offer? I was using rapamycin and stop because I did a PRP treatment and wanted nothing that might inhibit the associated healing.
"Walking the walk" is being a scientist and doing real science, not being a marketing online celebrity and not doing real science, mixing up variables and not knowing what effects are attributable to. You sound like the people who think the biggest guy in the gym is the only one to get training advice from, which is the dumbest take you could have.
Kaeberlein did a lot of the research this field is built on. He also appears to walk the walk in terms of lifestyle, just more scientific and less extreme than Johnson. Johnson has no credentials at all and seems to be in it for the cult-like following and money.
Brian is a grifter with a messiah complex. " Longevity mix ". " Extra special olive oil and chocolate powder ". He has this creepy little cult following of fanboys / girls nurturing his ego which is big enough to power a nuclear reactor.
@stx7389 So have you bought a lifetime supply of undutched chocolate and " high polyphenol count " Olive oil. I am fascinated to hear your response. Oh don't forget the " Longevity mix " make sure you catch that before stocks run low because obviously Brian has unlocked the key to resolving the nine hallmarks of aging in one swoop here. Or rather he has entered your bank balance kid.
I understand the analysis of the study and its limitations. I don’t think a discussion of his intentions is appropriate. He is well intentioned unless proven otherwise. There are zero indications he’s not well intentioned. He’s not getting rich off of blueprint.
It's funny to watch you complaining about someone dropping the use of Rapamycin, while no one has been able to show that Rapa is a longevity drug for humans and no one has defined the correct dosage for humans! Your complaints really go against any reasonable medical recommendations!👊
I don't think Matt complained about Johnson dropping the use of rapamycin per se, but pointed out that the reasons given for stopping it (the evidence presented and papers quoted) were complete bullshit. I suppose this stems from the fact that Matt is a scientist and expert in the field for many years, whilst Johnsons medical advice is Oliver Zolman who barely finished medical school, has no scientific pedigree and clearly difficulties in interpreting simple research. There is no hig quality evidence either way so I don't think a 'reasonable medical recommendation' exists for the use of rapamycin in this clinical context.
Did he really complain that he dropped it though? What I got from it is that he was voicing his distaste (could be construed as complaining). Towards Bryan using his large public forum to say that he was discontinuing the use of rapamycin because of factors that could not be confirmed to be due to the use of it as he also uses a plethora of other things. Which then he goes on to cite a reportedly very unreliable pre print. At the end of the video he states he thinks it’s fine Bryan stopped it.
Bryan rating his nonsense biomarkers and aging clocks over actual mouse studies shows that he lacks intelligence. Since human studies take too long, mouse studies are the best we can get.
I don't think it is that. I think it is more what Matt was saying about Johnson or his team misinterpreting the data. This does not rule out deliberately cherry-picking data, either. He is a multi-millionaire who employs a lot of scientists or medics but it is possible that Johnson's team is providing him with poor metrics. "Not everything that can be measured counts, and not everything that counts can be measured."
Any thoughts on having Michael Levin on the pod cast. This gets to the issue, is the field not making much progress because we are operating under the wrong paradigm. Perhaps Levins paradigm ( aging is controlled by the homeostatic influence of the bioelectric morphogenic network) could inform future directions of research. Thanks for the consideration Kevin Brown
@@inthegutterstaringathestars His medical team is akin to a watered down (for now...) version of Michael Jackson's physician, who was convicted of involuntary manslaughter after MJ overdosed on sleeping pills
4:51 "...that paper concludes that exercise doesn't work, healthy diet doesn't work, and rapamycin doesn't work..."
Those are not at all the conclusions of our pre-print. The pre-print investigates the responsiveness of epigenetic clocks, and is not really interested in the impact of any single intervention. The fact that many of these healthy life habits, such as diet and exercise, did not show a significant decrease in the epigenetic clock scores says much more about the epigenetic clocks than it does about the interventions themselves. Seems like you and Bryan Johnson entirely missed that point from the paper. It's not about the interventions - it's about the clocks. But thank you for the feedback, we'll need to emphasize this point as we rework it for submission for peer-review. Cheers!
I think you are doing a great job Matt. I really liked the way you explained the actual science, with regards to the studies. I totally agree with everything you said in this podcast. You're genuine, honest and unbiased.
MK and Nick - godsend! Frank, honest, bold, packed full of wisdom to those who will listen and consider. Thank you for giving me ideas to navigate health decisions.
Appreciate the kind words!
Always appreciate your clear-headed approach, Matt. This comes from and 80yo fan of your podcast, have used rapa for six years, extensive blood tests 4x/year show low lipids, ApoB 60 or lower. I believe that when finally extensive tests have been done about rapa and its side effects that it will have a different effect on different people. But certainly at this point it would be silly to make blanket statements. As always, thanks for your informative discussions.
I've really been enjoying your videos and your objective perspective on all this. There's so much out there on everything longevity related but difficult finding truly impartial voices. Much appreciated!
Hey Matt, stoked to have you covering our work. We would love to hear your thoughts on it more, I think it is tangentially related to your recent experiment with the multiple at-home biological age tests...
15:50 “the signal…isn’t strongly correlated with the things that promote health, so it’s hard to know what it means”
It's like you entirely get it one moment, and then entirely miss it the next. Our work was never intended to be interpreted as, "oh this intervention is actually crap, oh this intervention will help me live longer..." Our goal was to check something that no-one had never tested before: are epigenetic clocks responsive. Do they actually respond to anti-aging interventions?
I personally was shocked to see that many of the well known clocks (Horvath, Hannum) failed to pick up any change amongst 51 "interventions" (Figure 4B). Likewise, it's quite concerning that so many well known aging interventions, like exercise and diet, do not cause a significant decrease in epigenetic age across many clocks (Figure 3B), despite their documented correlation with lifespan. This is worth shouting about, and should drive further investigation!
Nowhere in our paper do we make any conclusions about the impact of a particular intervention on longevity. Rather, that the epigenetic clocks seem to be sensitive to some interventions more than others. Take Figure 3D for example, which makes this point well: the clocks seem more responsive to pharmacological than to lifestyle interventions. In the discussion, we hint that in some cases, this is likely due to a drugs direct effect on a specific biological pathway (as apposed to the systemic impact a lifestyle intervention may have).
Heated debate aside, we really appreciate you and the rest of the communities feedback. As we prepare our work for peer review, we will emphasize many of the points I've made here, and hope that will help sharpen our findings for future readers. Ultimately it is on us, the authors, to make our findings clear, and foresee the possible intellectual pitfalls that may arise when reading our work. Cheers!
Really appreciate this vid, I seen BJ had stopped and meant to dig into the data myself so saved me a lot of work!!
No rapa sides for me, 3 yrs,. Varying from 20mg to 6mg. No ldl issues and don't get sick. IMHO improved immune system. Good luck all.
Amazing review of the evidence and great discussion!!! Thank you!!!
Glad you enjoyed it!
Great video as always. Been waiting for this one ever since Bryan dropped that post on X.
crazy that this channel only has 13k subs. one of the best places for longevity info imo
Do you guys have any input on the new head (pending) of the FDA who is a believer in age-reversal and longevity science and how it will move along the field ??
Matt and I were talking yesterday about doing an episode on a topic similar to this. I’ll look into the new head of the FDA and get Matt’s opinion.
Thank you!
Nick
I posted 3 weeks ago about stopping rapamycin because my "bioage" got "older" not better with rapamycyn. To keep this simple, I'll show my changes in bioage relative to chrono age as time went on.
Right before starting rapamycin my bioage was -11 years ("younger)." After 7 weeks of rapamycin my bioage was again -11, so no change with rapamycin. But then after another 7 weeks, my bioage worsened to -6.5 years. After another 8 weeks on rapamylcyn my bioage worsened more to -6.0. So then I decided to stop taking it and wait another 7-8 weeks are do another blood test. This time my bioage recovered to -8.2. That's not back to my baseline -11 years but seems to be headed in the right direction. Now I know all the caveats about the bioage measures, but that's all I have to go on. You could quiz me about components of my blood work but that's what the bioage measures are based on. So I'm done with rapamycyn. The fact that it is so expensive also made the decision a little easier.
Says he doesn’t know anything about BJ, but still makes a lot of speculation about the validity of any of BJ’s findings. And he doesn’t seem to get the basic point that BJ is using himself as a data point by constantly testing himself to see if his changes are delivering the hypothesised results or not. As with Rapamycin, he’ll take 3 months off, get tested again, and see if the biomarkers changed or not.
Whenever the topic of longevity comes up I’m invariably asked what I think of Bryan Johnson. I always say - Sometimes you can spend so much time and money trying not to die that you forget to live.
yes but we can live while bryan johnson experiments and spends his money and tells us the results....so good luck to him...
This is so valuable. Thanks a lot for your amazing work!
Appreciate the support!
9:30: "He mentions resting heart rate decrease..." Actually it appears the tweet mentions resting heart rate *increase." Important difference, as all else being equal a resting a heart rate decrease would be an indicator of increased health, whereas an increase would imply decreased health.
It decreased when he got off of Rapamycin, indicating Rapamycin was somehow increasing his RHR. Which I agree would be a negative effect if true.
- Nick
I have gotten sick every time I try rapamycin, plus I get acne.
Thanks for the response - very helpful!
I have considered taking Rapamycin because I've heard it may regrow pariodontal bone. Matt, what is your understanding on this issue? Thanks
Your take on the cosmetics industry anti-aging claims and negative effects of applying all those chemicals would be very interesting. Thank you!
I stopped Rapamycin when my "bioage" got worse relative to my chrono age after taking it. I'm going to retest soon after about 10 weeks abstinence. I'll reconsider when I get the results.
Caveat: I know about the limits or even the legitimacy of the various bioage measures.
Watch Matt's tearing apart the age tests. 99% noisy results.
@MsElaine122 I have. That's why I'm not sure of anything. But none of us are sure of Rapamycin, so maybe I should err on the side of caution. I'm old anyway, so I don't have a lot of longevity potential. I have to take all of this into consideration.
@@bill9989 You could look for improved general health marks, rather then agetest. If more health marks improve then get worse (at least if those getting worse isn't moving into harmful ranges), it probably a net positive
@zombi3lif3 Thanks, but I'm all over my health indicators. Before rapamycin, my bioage was 11 years "younger." After 20 weeks on, my bioage dropped to 6 years "younger." Again, I know these tests aren't validated. But also, my fasting glucose went up a little bit, but my triglycerides went up significantly.
I don't know how much Dr. Oliver Zolman is involved with Bryan Johnson's selections of therapies, but this Doc has made some strange comments in his videos - some of which make one question what kind of doctor he actually is.
It fits perfectly with Johnsons claims of being science based. He pretty much done the same protocol from the start, claiming everything have had to fight for it's place in the protocol. I don't believe he ever taken the time, to test every intervention by itself.
It looks more like a forced from day one protocol. Particularly when compared to Michael Lustgarden, from Conquer aging or die trying, who been posting his quest for the perfect protocol, for 3-4 years, and he is still do adjustments to improve his data
I'm curious if taking a very small dose of rapamycin (e.g., 1mg/weekly) with grapefruit juice would be equivalent to a 3-4mg/weekly dose of Rapamycin alone.
I really need this, Im not even done watching but I know I need this.
Stay away from new experimental stuff NMN caused me a benign kidney tumour
I might need @Physionic level explanation of some of this.
It makes sense if you consider what might be coming next. A Blueprint custom rapamycin. Follow the money $$$$
BJ is about making the protocol easier for people, he wouldn't get into pushing a prescription drug
@stephaniehendricks225 currently he does that by offering blueprint mri that costs sonipat three times as much as others
Appreciate the video! If we're allowed to pick on one thing, I'd say to refrain from character assassinations. We're here for the scientific takes, not the mud throwing.
I appreciate the feedback and agree, will do our best to avoid character assassinations and other fallacies.
- Nick
@MusixPro4u Not sure why you are here but it is your opinion not everybody elses ie do not speak for others and it seems like the only one attempting "character assassination" and "mud throwing" is you. Also, any opinion using a psedonym (no name) makes it questionable to say the least. I would bet that 99,9% of the viewers and subsribers appreciate the healthy skepticism and the deep dives into (and irony of) what various "influencers" are pushing to people which usually involves some products. There is none of that here and it is so appreciated by myself I absolutely love Matt Kaeberlein and the work he is doing for free on this channel ❤
@@optispan Please continue doing the awesome work you do on this channel including the healthy skepticism ❤ It is very much needed in this day and age where various individuals are pushing products and other stuff (which in my humble opinion automatically discredits them from the very start).
One of the best TH-cam channels for true longevity, information, and science. Well done. Only minor issues with bias or name calling compared to all others.
@@anita.popovicOdakle si ? Čudno mi je vidit nekog iz Balkan regije zainteresiranog za ovakve teme.
If he is methionine restricted and calorie restricted, why do you think is so crazy to stop taking rapamycing?
I'm guessing the soft tissue infections might include the mouth sores/ulcers I have heard some people attribute as a side-effect, but who knows.
Great podcast!
If he stopped taking it and those side effects went away…you wouldn’t think it’s logical to assume that rapa was causing it?
Thanks for another interesting video. I did find it entertaining. I have followed Bryan Johnson and I tend not to be influenced by him, because I see his journey as a personal experiment that apart from eating healthy and exercise I would be wary on considering the rest
The pre-print data includes a "rapa dose 3" that showed "accelerated" aging. You didn't mention this in your video...I think that's what Bryan was referring to.
I (64) have been taking 5mg Rapamycin once every 6 weeks for 6 years. Although Johnson says (based upon that post, I don't follow him) he tried different doses of R, all those doses were on the high end of the spectrum, very high considering his body weight, for anti-aging, I don't understand why he would not have just changed to an intermittent dosing schedule like mine. Sorry to hear about Dr Green, fwiw when I met with him 6 years ago he was very frail. I am skeptical Johnson had been taking R for 6 years.
Does Bryan Johnson red light therapy for hair growth and skin rejuvenation work? Could be a good podcast.
I think you definitely have Bryan Johnson on. He says, "You don't have to buy my products; you do you." He might not be deliberately disingenuous, but may have biases influencing his decisions to be a big influencer and merchandiser.
I’m going to reach out. We’re traveling to California in February, I’ll see if we can connect with Bryan while we’re there.
- Nick
@@optispan That would be great. He spends $2 million a year on research. He promotes for humanity, "Don't die." Can his regimen and products impact the things that contribute to death: telomere shortening, epigenetic drift, mitochondrial decline, and genomic instability? I also think Dr. Mike had a great idea that one person is a single study, but a scientific study of 15 people, would quantify his goals.
Some people should be careful
LEARNING POINTS
Ketamine use disorder can lead to severe cardiovascular complications, including acute systolic heart failure, likely due to its direct negative inotropic effects and dose-dependent impact on cardiac function.
Clinicians should consider screening for ketamine use disorder in young adults presenting with acute systolic heart failure, especially when other common aetiologies have been ruled out.
Early recognition and prompt treatment of ketamine-induced heart failure with diuretics and guideline-directed medical therapy can lead to significant improvement in cardiac function, but long-term management should also focus on ensuring cessation of ketamine use disorder.
Guide to popular people in longevity and their positive biases:
Charles Brenner - NR
Sinclair - Resveratrol
Peter Attia - Exercise
Kaeberlein (my goat) - Rapamycin
One thing I appreciate about people who take their personal longevity to extreme lengths (Bryan Johnson, ConquerAgingOrDieTrying) is that they clearly *really* do not want to die. As far as I can tell, I think they are really trying to find the truth of what will actually make them live longer (rather than defending their status or research or career). Of course, Bryan now has heavy financial incentive to defend the validity of certain things he sells, but in his case I'm not super bothered by that because he's already rich and he comes across as genuine and truth-seeking in his longevity obsession.
This is not a knock on Dr. Kaeberlein. I'm only 10min in to the video. I just noticed that the doc is inclined to be more skeptical of Bryan's intentions than I am (maybe rightfully so).
Kaeberlein's main recommendation is not rapamycin, he recommends the basics like physical exercise, sleep, superior nutrition and social connections.
@@PakistanIcecream000 yeah thats not contradictory to my comment
Even if Bryan Johnson lived to be 130, how would we be able to tell which (if any) of his hundreds of different interventions did anything? I don't see at all how what he is doing leads to any useful information. Yes, he may have shown that certain biomarkers change, but the impact of those biomarkers on human healthspan and longevity is still an open question.
@@persistenthomology It's a good point, for sure. But I don't see Bryan's project as a way to increase our knowledge on longevity, but rather as a way to generate interest, hype and investment in longevity research.
I, too, fully appreciate Dr. Kaeberlin, but to be fair, he is always a bit skeptical in his approach. When I disagree with him, I’m forced to defend my own position. He’s more than a valuable asset to this community. As for Stansfield, he tries too hard to be one of the big boys.
Bryan Johnson is going to turn into a gamma ray infused green monster. He is a real case study.
Excellent content! Can the use of testosterone and GH contribute positively to longevity?
Just some off the cuff remarks: BJ has been doing Rapa for 5 years now, so I guess he's been trying different dosages and protocols during that time, while checking what's the impact on his biomarkers. Just guessing here, but I don't think he just stopped because of this study. We don't know yet if there are nefarious motives for BJ actions, but we can't also ignore that Matt has a horse in this race. Anyway as for the study itself, haven't looked into the pre print but still I find it interesting that calorie restriction and exercise don't correlate with longevity (if I got that right about what you were saying). And while it flies in the face of most we know, it still leaves me wondering if there's something here. I've seen my share of centenarians and talked with some of them, and usually there's not a background of athletic pursuits. Sure, most led active lives till they could, but nothing "crazy" like running 4 hours every week. And usually they don't eat that much when older, but don't feel like they are in CR, they just don't expend that much anyway at that age. Sure, they don't overeat and since they are in nursing homes (the ones I have contact with), that means they have regular meals, healthy but also with some desserts thrown in or maybe a cookie before bed. And yes of course, usually medium-short females, not overweight.
Haha you really seem to not like Bryan Johnson. I hope you can meet soon and look into his eyes and then tell us what you think after. I am so torn and I just don't know anymore.
The longer you live the more likely horrific a death will be high. Plus if he lives to 200, how many of those years will he be capable of moving fluidly like he or a younger person can. If he becamebv a quadriplegic or paraplegic or brain damaged at age 120, the next 80 years are gonna be horrible.
The saltiness was not a good look. It just felt as if you were ignoring Hanlon's razor and Hitchen's Razor the entire time.
There wasn't any saltiness at all, he took great pains to not make it personal and to support Brian's personal decision whilst separating that from the supposed logic behind it. Matt covered both possibilities - that Brian could simply be making a bad decision with bad interpretation of his results, OR that there might be a bad faith marketing component to it. He openly said many times he did not KNOW, but addressed these as possibilities for people to consider. In terms of the available evidence, it would seem to be Brian who has not limited his variables to show that what he is attributing to Rapa is actually attributable to it. So neither of your razors apply.
I quite enjoy your presentations, Matt. IMO, however, they would be considerably improved if you would teach yourself to stop saying "again" over and over. Thx for considering.
For best epigenetic test results he might use some tnf alpha inhibitors
Especially he is a male, some data do show most beneficial for female only
Great video and insights on the "blueprint" that Bryan Johnson is promoting! As far as I can see from his case the most visible effects has been from doing various cosmetic procedures (skin, hair) which also inbcludes fat transfers. When it comes to the not dying part I guess time will tell.
That effects was caused by with very specific causes/needs and has nothing to do with his biomarkers or organ scans
I never take rapamycin. But roxythromycin 300 mg.
Sorry why was he taking rapamycin in the first place? It’s an antibiotic. He was taking an antibiotic for five year’s continuously? What is the science behind that?
It started as something you gave patients when doing organ transplant. But then scientists realized it increased longevity when giving it at low(er) doses, one time a week or something like that. It's an mTOR inhibitor, so that might explain the effect. It also appears to work in all classes of animals that have been studied so far(mice, worms, etc). Lots of YT videos around that explain it better than I can, but that's the gist of it. At this time everyone that is taking it, is doing it on faith so to speak, and mostly because it didn't appear to have any nasty side effects, so why not. The most common are mouth ulcers, which is probably what Bryan is referring to with the "soft tissue infections". Having Bryan stopping this after 5 years, might signal that "something is off" about rapamycin.
Why take for 5 years a drug causing you such side effects? His team 🤔Those side effects he has for years.. yet they only tell him now to stop 🛑 it ? I'm concerned for Bryan Johnson!
Just fast! It's free.
they ignored the drop in RHR after dropping rapa. I've feen a follower of the sub for a while and all I see if bad outcomes like increased hba1c in younger participants. My guess it's good to downregulate mtor at a much older age 60+, Bryan is still young enough not to have those issues.
I too have heard of increased glucose related biomarkers in young people, along with some horror stories related to side effects.
Sounds like the gentleman has a dog in the fight. Why belittle the guy who is reporting why he is no longer taking it. I would have just said " There's no way of him knowing exactly what was causing his side effects or lack of positive effects without having scientifically measured the variables and perhaps not that he is lying.
Why take for 5 years a drug causing you such side effects? His team must be really bad! Those side effects he has for years.. yet they only tell him now to stop 🛑 it ? I'm concerned for Bryan Johnson!
He didn't belittle him at all, he just raised the possibility that an internet personality might not be telling you the unvarnished truth, and might be marketing based on the personality he has invented, which is way more than a slight possibility and the kind of thing way more people need to hear these days. Note that Matt also said that where he stands on it has never been to make positive claims about it, but that there are some positive indications and that the trials need to be done to see what the real deal is. Why are there so many people in this comment section who have such poor comprehension of what was said?
@@PinataOblongata I do think you are right- you may have a poor comprehension of what was implied.
Sorry but I'm gonna put my faith in Bryan who's walking the talk and not you. What credentials do you offer? I was using rapamycin and stop because I did a PRP treatment and wanted nothing that might inhibit the associated healing.
are you dumb. genuine question
"Walking the walk" is being a scientist and doing real science, not being a marketing online celebrity and not doing real science, mixing up variables and not knowing what effects are attributable to. You sound like the people who think the biggest guy in the gym is the only one to get training advice from, which is the dumbest take you could have.
@ Point to a single longevity study in humans showing a benefit.
@@ScottSummerillStupid comment. There have not been any "longevity studies" in humans.
Kaeberlein did a lot of the research this field is built on. He also appears to walk the walk in terms of lifestyle, just more scientific and less extreme than Johnson. Johnson has no credentials at all and seems to be in it for the cult-like following and money.
Brian is a grifter with a messiah complex. " Longevity mix ". " Extra special olive oil and chocolate powder ". He has this creepy little cult following of fanboys / girls nurturing his ego which is big enough to power a nuclear reactor.
Nonsense, he is not grifter
@stx7389 So have you bought a lifetime supply of undutched chocolate and " high polyphenol count " Olive oil. I am fascinated to hear your response. Oh don't forget the " Longevity mix " make sure you catch that before stocks run low because obviously Brian has unlocked the key to resolving the nine hallmarks of aging in one swoop here. Or rather he has entered your bank balance kid.
I understand the analysis of the study and its limitations. I don’t think a discussion of his intentions is appropriate. He is well intentioned unless proven otherwise. There are zero indications he’s not well intentioned. He’s not getting rich off of blueprint.
It's funny to watch you complaining about someone dropping the use of Rapamycin, while no one has been able to show that Rapa is a longevity drug for humans and no one has defined the correct dosage for humans! Your complaints really go against any reasonable medical recommendations!👊
Cult over Science
🎯
I don't think Matt complained about Johnson dropping the use of rapamycin per se, but pointed out that the reasons given for stopping it (the evidence presented and papers quoted) were complete bullshit. I suppose this stems from the fact that Matt is a scientist and expert in the field for many years, whilst Johnsons medical advice is Oliver Zolman who barely finished medical school, has no scientific pedigree and clearly difficulties in interpreting simple research.
There is no hig quality evidence either way so I don't think a 'reasonable medical recommendation' exists for the use of rapamycin in this clinical context.
Nobody said it works for humans. You'd need to study humans over a 100 years to do that. Your point is nonsense.
Did he really complain that he dropped it though? What I got from it is that he was voicing his distaste (could be construed as complaining). Towards Bryan using his large public forum to say that he was discontinuing the use of rapamycin because of factors that could not be confirmed to be due to the use of it as he also uses a plethora of other things. Which then he goes on to cite a reportedly very unreliable pre print. At the end of the video he states he thinks it’s fine Bryan stopped it.
Bryan rating his nonsense biomarkers and aging clocks over actual mouse studies shows that he lacks intelligence. Since human studies take too long, mouse studies are the best we can get.
I don't think it is that. I think it is more what Matt was saying about Johnson or his team misinterpreting the data. This does not rule out deliberately cherry-picking data, either.
He is a multi-millionaire who employs a lot of scientists or medics but it is possible that Johnson's team is providing him with poor metrics.
"Not everything that can be measured counts, and not everything that counts can be measured."
Any thoughts on having Michael Levin on the pod cast. This gets to the issue, is the field not making much progress because we are operating under the wrong paradigm. Perhaps Levins paradigm ( aging is controlled by the homeostatic influence of the bioelectric morphogenic network) could inform future directions of research.
Thanks for the consideration
Kevin Brown
@@inthegutterstaringathestars His medical team is akin to a watered down (for now...) version of Michael Jackson's physician, who was convicted of involuntary manslaughter after MJ overdosed on sleeping pills
Yeah biomarkers are nonsense 😂😂😂
@@stx7389 thats what i said. learn to read lmao.