Todd Allen Posted March 17 Report Share Posted March 17 https://www.thelongevitynewsletter.com/p/david-sinclair-matt-kaeberlein Quote I find it deeply distressing that we’ve gotten to a point dishonesty in science is normalized to an extent that nobody is shocked when a tenured @Harvard professor falsely proclaims in a press release that a product he is selling to pet owners has “reversed aging in dogs”. To me, this is the textbook definition of snake oil salesman. Matt Kaeberlein, University of Washington Quote Link to comment Share on other sites More sharing options...
TomBAvoider Posted March 18 Report Share Posted March 18 I'd just like to point out, that I have been way, way, WAY, ahead of the curve when it comes to Mr. Sinclair. From the beginning, when he first came onto my radar years ago, at the start of the resveratrol hype, I pegged him as a snakeoil salesman, simply based on his classic shyster MO - he checked off all the boxes that identify such operators, and I denounced him as such. Btw. his mouse studies never showed max longevity benefits of resveratrol, at best a normalisation of lifespan in obese mice, and since then doubt has been cast on those studies too. There was nothing there, let alone grounds for wild claims. He certainly made out like a bandit in the stock buyout of his scientifically worthless biotech company, and has been a supplement pusher with one dubious pill after another. The man has been a shameless huckster spinning his money making schemes for so long now that it's a real puzzle as to why anyone would buy a single thing from his recommendations. Hypersters have existed long before PT Barnum cashed in from the suckers, but as he observed, a new sucker is born every minute. And we live in a time of extraordinary proliferation of HYPE, as we see every day in the headlines and breathless reporting about the next grand revolution that will radically change human history and achieve perpetual motion based on AI self-driving fusion powered quantum computers that will upload your brain into immortality on Mars, blah, blah, blabbity blah. Good on Matt, for calling out Sinclair, but sadly there's an endless supply of these hypesters, just as there is of the suckers who listen to them. Quote Link to comment Share on other sites More sharing options...
Dean Pomerleau Posted March 18 Report Share Posted March 18 "Harvard professor falsely proclaims in a press release that a product he is selling to pet owners has “reversed aging in dogs”. To me, this is the textbook definition of snake oil salesman." Says professor at another university pushing rapamycin as a cure for aging in dogs... Lol. Quote Link to comment Share on other sites More sharing options...
TomBAvoider Posted March 18 Report Share Posted March 18 10 hours ago, Dean Pomerleau said: "Harvard professor falsely proclaims in a press release that a product he is selling to pet owners has “reversed aging in dogs”. To me, this is the textbook definition of snake oil salesman." Says professor at another university pushing rapamycin as a cure for aging in dogs... Lol. To be fair, Matt is very careful and nuanced in making any claims for rapa. I've listened to many hours of his interviews on many podcasts, and he certainly is careful not to hype rapa, so he definitely is not your classic hypester. And the fact is, that unlike for most of the supplement/pharmaceuticals out there (certainly resveratrol!), rapa actually has some very solid results, and Matt's studies are well designed. So cautious optimism wrt. dogs and rapa seems not unwarranted. Of course we still need to wait on more results, and caveats always apply, but if there is such a thing as scientifically and ethically sound studies (and we all better hope there is!), then I feel Kaeberlein qualifies. Clearly, this doesn't mean rapa research in mice or dogs necessarily translates to humans (especially that mice were exposed to massively larger doses than humans), and Matt to his credit never pushed rapa in humans - this remains a personal call and a deliberate gamble - which includes your pet - (I think Kaeberlein personally takes it), so you get to roll the dice as you see fit. I'm obviously not opposed to the search for longevity interventions, just opposed to hype and hucksterism. Insofar as Sinclair and Kaeberlein are concerned I think they belong on the opposite sides of this divide. YMMV. Quote Link to comment Share on other sites More sharing options...
mccoy Posted March 19 Report Share Posted March 19 On 3/18/2024 at 11:31 AM, Dean Pomerleau said: Says professor at another university pushing rapamycin as a cure for aging in dogs... I think the subtle irony did not escape Dean who rightly underlined it, regardless of other aspects. 17 hours ago, TomBAvoider said: Clearly, this doesn't mean rapa research in mice or dogs necessarily translates to humans (especially that mice were exposed to massively larger doses than humans), and Matt to his credit never pushed rapa in humans - this remains a personal call and a deliberate gamble - which includes your pet - (I think Kaeberlein personally takes it), so you get to roll the dice as you see fit. Hasn't rapa been tested on humans? Or some major clinical trial is ongoing or in project? I think I read something from NUS (University of Singapore) which has a strong gerontology department. Quote Link to comment Share on other sites More sharing options...
Todd Allen Posted March 19 Author Report Share Posted March 19 On 3/18/2024 at 2:40 AM, TomBAvoider said: I'd just like to point out, that I have been way, way, WAY, ahead of the curve when it comes to Mr. Sinclair. Indeed, I was a bit swayed by your arguments but hoped you were overstating your case. Unfortunately now I'm increasingly inclined to believe you were right on the money. I also am less concerned about Matt's research with rapa and dogs. If it leads to him profiting from pet foods, supplements or medicines then I will reconsider but for the moment I have the impression he is more interested in science then self enrichment. Quote Link to comment Share on other sites More sharing options...
Todd Allen Posted March 19 Author Report Share Posted March 19 4 minutes ago, Todd Allen said: I also am less concerned about Matt's research with rapa and dogs. If it leads to him profiting from pet foods, supplements or medicines then I will reconsider Yikes! I just found this: https://helpingpetslivelonger.com/ I don't think Matt has any connection to it other than providing data and visibility but it does illustrate how easy it can be to cash in on any longevity related research. Quote Link to comment Share on other sites More sharing options...
Dean Pomerleau Posted March 19 Report Share Posted March 19 19 minutes ago, Todd Allen said: Yikes! I just found this: https://helpingpetslivelonger.com/ I don't think Matt has any connection to it other than providing data and visibility but it does illustrate how easy it can be to cash in on any longevity related research. Only $100 per month for rapamycin to keep your dog young and healthy... "Although we don’t have all the answers yet, rapamycin appears to be the single best way to prolong not just lifespan, but also the general health of all mammals studied to date!" Lol. Quote Link to comment Share on other sites More sharing options...
Todd Allen Posted March 19 Author Report Share Posted March 19 1 hour ago, Dean Pomerleau said: Only $100 per month for rapamycin to keep your dog young and healthy... $105 for 12 0.5 mg capsules or $112 for 12 3.0 mg capsules. Considering the empty capsules cost maybe $0.20 and filling them can be automated suggests to me the pricing has little to do with costs. I'm guessing the calculation is that even at $10 the market would be tiny so let's make as much per customer as possible. Quote Link to comment Share on other sites More sharing options...
Todd Allen Posted March 19 Author Report Share Posted March 19 1 hour ago, Dean Pomerleau said: rapamycin appears to be the single best way to prolong not just lifespan, but also the general health of all mammals studied to date! According to the FDA, you are not a horse. And probably not a dog either. So all you longevity peeps don't go getting any bright ideas about achieving escape velocity with dog paste... Quote Link to comment Share on other sites More sharing options...
TomBAvoider Posted March 19 Report Share Posted March 19 1 hour ago, Todd Allen said: Yikes! I just found this: https://helpingpetslivelonger.com/ I don't think Matt has any connection to it other than providing data and visibility but it does illustrate how easy it can be to cash in on any longevity related research. Right. I don't think Kaeberlein should be responsible for every random person grabbing his research to make money. As long as he dosn't profit or in any way endorse those schemes, of course. He may not even be aware of this person, but yes, how to disassociate yourself from such folks becomes a full time job. The dog studies to date are suggestive, but have not been completed, so a lot of work remains before one can even begin to think of clearing rapa for dog longevity indications. Naturally, desperate pet owners will grab onto any hope, so any preliminary results should always come with plenty of caveats, cautions and warnings. Quote Link to comment Share on other sites More sharing options...
TomBAvoider Posted March 19 Report Share Posted March 19 28 minutes ago, Todd Allen said: According to the FDA, you are not a horse. And probably not a dog either. So all you longevity peeps don't go getting any bright ideas about achieving escape velocity with dog paste... Understandable caution, but isn't the whole longevity endeavor on big gamble? Given the limitations of conducting human lifespan intervention studies (an RCT trial running 100+ years anyone?), there isn't a single human such study, nor will there ever likely be one. All you'll ever have is animal studies at best (monkey studies of 40+ years), so you either take a more or less well calculated gamble based on animal results or give up alltogether since the FDA can't clear any such drug for humans given that no such studies will be conducted. Some folks have decided that rapa is a worthwhile gamble, and perhaps the dog studies were a factor in such decisions. Few things are a certainty in medical science, so if someone wants to gamble on some intervention I would not condemn them. Isn't the origin of this very board and website the result of such a gamble by CR enthusiasts? It's all a gamble. And as gambles go, rapa seems not the worst of it - there are some human rapa-analogue results (immunity related) that may be suggestive, and no evidence of harm (to this point) other than minor ones like canker sores, so as far as drug interventions go, you could do worse. Obviously it's a gamble and nothing is certain (not even dosage!), but hey, it's either that, or do nothing. We could wait for more studies of rapa analogues, but time marches relentlessly, and not all of us have the luxury of waiting. You take your shot, and the chance that you may shorten and worsen your life, or do nothing. Each of us has to make that decision on their own. Quote Link to comment Share on other sites More sharing options...
Todd Allen Posted March 20 Author Report Share Posted March 20 7 hours ago, TomBAvoider said: Obviously it's a gamble and nothing is certain (not even dosage!), but hey, it's either that, or do nothing. It's not really rapa or nothing. Most agree there are fundamentals such as diet, sleep, exercise, stress management, toxin avoidance, positive relationships, etc. which can get one pretty far despite a lack of agreement on the precise details. I didn't mean to say no one should self experiment with rapa but rather I think getting this particular vet to prescribe it for your dog and buying pills from him is a really bad idea. Especially if one doesn't have the capacity to verify what exactly is in the capsules one might get. Does he expect repercussions if his pills do nothing and people's dogs still age and die at the same rate? I have more confidence a major brand horse paste will have the ingredients claimed. I am also mocking the FDA and I place no value on anything that corrupt incompetent agency says or does. Quote Link to comment Share on other sites More sharing options...
Gordo Posted March 20 Report Share Posted March 20 16 hours ago, TomBAvoider said: no evidence of harm (to this point) other than minor ones like canker sores So being on immunosuppressive drugs 24/7 for life has no downside? Who needs an immune system anyway? 🤔 Quote Link to comment Share on other sites More sharing options...
mccoy Posted March 20 Report Share Posted March 20 3 hours ago, Gordo said: So being on immunosuppressive drugs 24/7 for life has no downside? Who needs an immune system anyway? 🤔 I think TomB referred to the current practice of intermittent dosage, with small doses like 5 or 10 mg every week or 10 days. AFAIK, current issues are cost, availability, and availability of doctors who prescribe. I still would not accept mouth ulcers, but they don't manifest in everyone and dosage may be decreased in such a case. Quote Link to comment Share on other sites More sharing options...
TomBAvoider Posted March 21 Report Share Posted March 21 12 hours ago, Gordo said: So being on immunosuppressive drugs 24/7 for life has no downside? Who needs an immune system anyway? 🤔 As you know, the ancient rule applies: "dose makes the poison". Rapa is/was used as an immunosuppressant in organ transplants, but at lower doses it has been documented (human trials of a rapa analogue showed enchanced immunity against infectios agent, augmenting effectiveness of vaccinations) as an immune system rejuvenant. There also appears to be some evidence of cancer suppresion. All in all, an enchanced and rejuvenated immune system appears to be one of the most prominent effects of rapa (and its analogues). Again, however, dosage is critical, and unfortunately this is very unclear insofar as there are no validated dosage protocols for longevity and health promotion in humans. It is also possible that the optimal dosage may have a pretty narrow range (i.e. there isn't much of a safety margin), you derive benefits in a somewhat small window. Also absorbtion is an issue, and early experiments in mice failed because straight rapa wasn't assimilated at all - you need a pharmaceutical formulation for it to work (which is why FDA approved rapa analogues are preferred by many). And as I mentioned, there is a great deal of uncertainty because the effective equivalent dosages in mice are drastically higher and would be toxic in humans, which puts a big question mark over the entire enterprise in people - it would't be the first time when an agent that works great in animals fails completely in humans. There's growing suspicion that rapa would work best in humans combined with other agents. And perhaps there will be modified rapa derived agents that would work better (centered around suppressing complex I while sparing complex II). Bottom line, it's very early days for rapa use in humans for longevity/health purposes, and at this time remains a highly speculative endeavor. But as I said, there's the pressure of time, and not all of us have the luxury of waiting on more solid scientific evidence, and some may feel forced to gamble. Quote Link to comment Share on other sites More sharing options...
Saul Posted April 13 Report Share Posted April 13 On 3/20/2024 at 8:33 AM, Gordo said: So being on immunosuppressive drugs 24/7 for life has no downside? Who needs an immune system anyway? 🤔 Gordo, The immune suppressive factor in rapa is negligible for helthy people; so it's conceivable that rapa might be interesting. I asked Matt when he gave a talk at the University of Rochester's annual aging conference, whether he thought that CR and rapa might go together. He said that he never could get funding for such a study. The dog study is possible, since it simply depends on large dog owners volunteering to allow their pet to enter the study. Since large dogs have short lifespans, there hopefully might be some useful data in not too long a time period. If, as Matt suspects, rapa appears to improve the expected lifespan and heathspan of large dogs, it would certainly be interesting. -- Saul Quote Link to comment Share on other sites More sharing options...
mccoy Posted Tuesday at 06:09 AM Report Share Posted Tuesday at 06:09 AM For those who are interested into the aspect of human immunity and rapamycin, in this episode of his podcast MAtt Kabelrlein and his guest venture at a point (after the first part on senscent cells) into the effects of Rapa on NK cells and T cells. It is as usual a very complex system with cells having a mTOR pathway which seems to be optimized differently than other cells in the body. Their final answer, I guess, is that presently there is no answer and clinical trials should be carried out. Quote Link to comment Share on other sites More sharing options...
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