Rapamycin Anti-Aging Medicine: An Interview with Alan S. Green, M.D.

Dr. Alan Green

Rapamycin, a drug used as an immunosuppressant in the treatment of organ transplant patients, may be the most potent life-extension drug currently available, and the practice of rapamycin anti-aging medicine is just getting started.

Mikhail Blagosklonny, a doctor and scientist at the Roswell Park Cancer Institute in New York, has been the most notable and vocal advocate of rapamycin to extend human lifespan. While rapamycin has adverse side effects in humans who take it daily for immunosuppression, recent research has found that pulse dosing, perhaps once a week, may confer most of the anti-aging benefits without any adverse side effects.

Will rapamycin fight aging in humans and extend lifespan? Unfortunately, clinical trials of rapamycin for this purpose are unlikely to happen any time soon, but some people would like to find out. Among them was Alan S. Green, M.D., who practices medicine in New York state, and who, beginning in early 2016, began to take rapamycin himself, along with metformin, an angiotensin blocker, and aspirin.

At the age of 72, Dr. Green found himself suffering from old age:

I attended college on a tennis scholarship and ran a marathon in just under 4 hours at age 40. But by age 70 my main physical activity was reduced to walking my two Shiba Innu dogs in the park. Then by age 72, I experienced angina and shortness of breath on small hills. As a trained pathologist I accepted the reality that I was in rather poor shape. My fasting blood sugar was up, my creatinine blood level was elevated indicating renal insufficiency and I couldn’t fit into any of my pants. I then began trying to learn about aging. I discovered a story more extraordinary and improbable than anything I had ever encountered in my lifetime.

He began to take rapamycin on a weekly dosing schedule, along with the other drugs noted, and after only 4 months, he experienced vastly improved health.

Based upon empirical medicine principles, I decided rapamycin 6 mg once a week would be an  aggressive treatment and 3 mg once every 10 days would be a conservative treatment. I decided to go with aggressive treatment. January 2016, I began the rapamycin-based Koschei formula with intent to take it for one year; in what could euphemistically be called a “proof-of-concept” experiment.  I didn’t have to wait one year; by 4 months the results were miraculous. I lost 20 pounds,  my waist-line went from 38 inches to 33. I bought a pair of size 32 jeans and didn’t have to wear joggers no more. I could walk 5 miles a day and ride a bike up hills without any hint of angina. Creatinine went from elevated to normal and fasting blood sugar went down. I thought I was Lazarus back from the dead. It’s now over 1 year and I feel great. I’ve also had no mouth sores, the most common clinical side-effect. For me, rapamycin is the world’s greatest medicine. [My emphases.]

Dr. Green reports: “Subjective impression: Miraculous improvement in health; feeling old to feeling young.” 

Dr. Alan S. Green

Given all of this, and after reading through his website, I decided it would be a good idea to interview Dr. Green, and he graciously consented to it. This is a tremendous interview with Dr. Green, who appears to be the only physician in the world practicing anti-aging medicine with a rapamycin-based treatment regimen, arguably the most potent life-extension intervention currently known.

As a practicing physician, Dr. Green has translated the scientific research on anti-aging and life extension and put it to work on humans, and as such, he’s a true pioneer in medicine. I predict that the approach he uses will become more widespread, and quickly. While Silicon Valley startups and tech moguls reach for unproven and perhaps even phantom methods to fight aging, and are pouring lots of money into the effort, Dr. Green shows that potent anti-aging medicine is here now, and you don’t need to be a billionaire to afford it. (Are you listening, Peter Thiel?)

Following are my questions and Dr. Green’s answers.

P. D. Mangan: You said that earlier in life, you were physically active, having run a marathon at age 40. When you found yourself feeling the effects of aging at age 72, is there anything that prompted you to turn to rapamycin and other anti-aging drugs rather than trying to become more active again and/or changing diet? Did you feel that physical/dietary changes wouldn’t be adequate for the health problems you were facing?

Alan S. Green, M.D.:  My point was I had been in good shape with jogging and tennis so when I started going down hill it was very apparent. At about age 67 I stopped playing tennis due to slowness and fatigue. I tried to control increasing size of waist line with diet but without much success. However, I viewed all changes as normal aging which was the traditional medical view. It wasn’t until age 72 when I developed angina and SOB walking up small hills in the park with my 2 Shiba innu dogs, that I finally concluded that I had a progressive fatal disease and that disease was aging. As I didn’t know anything about aging, I had no reason to consider diet or exercise as a remedy. My plan was to study aging to determine if there was any treatment.

PDM: I’ve learned a great deal from Mikhail Blagosklonny myself, have read all of his aging theory papers, and believe his quasi-programmed theory of aging makes more sense than almost anything else out there. Yet there are many other theorists of aging. Why did Blagosklonny’s ideas resonate so much with you? Did you come across other theorists who weren’t as convincing?

ASG: I believe in science, not metaphysics so “theories” not supported by scientific facts mean nothing to me. The start of understanding aging is that rapamycin increases life span of all living things and mean life span of mice by 25%. Further study showed that rapamycin blocked almost all key steps in progression of atherosclerosis and rapamycin prevented development of Alzheimer’s disease. Furthermore, mTOR was the command and control of all cells of all living things. Blagosklonny had a theory which explained how reducing mTOR slowed aging and slowed diseases of aging, so this was very interesting theory as it dealt directly with mTOR. Blagosklonny also had an anti-aging treatment plan for reducing mTOR. I was impressed with Blagosklonny enough that his treatment plan was certainly worth a shot. After 4 months of the rapamycin based treatment, my body had undergone what I considered a miraculous change and I felt cured. Being cured was what resonated with me. Today I went for a 40 mile bike ride with a stiff headwind. I felt perfectly fine and when came home I took my dogs for walk in the park and those small hills which once caused angina now seemed like nothing more than Gopher mounds. So it is not the Blagosklonny theory which impressed me; but rather the results.

PDM: A very large number of Americans, perhaps as much as 80%, have some degree of insulin resistance, i.e. they’re not in optimal health, and around the same fraction are overweight or obese. Do you have an opinion as to what degree the diseases of aging, such as heart disease and cancer, may be due to these factors, and to what degree they are strictly caused by old age?

ASG: I believe aging is a bundle of many disease mechanisms; but the most important one in the 60-95 age range is elevated mTOR. I would estimate that in general 75% of aging and age related disease in this age group is due to elevated mTOR. Specifically with atherosclerotic cardiovascular disease it is probably closer to 90% and with cancer probably less than 50%.

PDM: Do you think that rapamycin treatment will become widespread in the near future? What are the obstacles, if any, to it becoming more widely adopted?

ASG:  Rapamycin may become more widespread; but probably not. The obstacle is lack of appropriate human trials. Rapamycin will never be an “on label” drug. Furthermore, rapamycin has been used by over a million people as a biologic poison in transplant medicine. It will be very difficult to overcome the bad name it has received in transplant medicine. Rapamycin is type-cast as a bad guy. Use of rapamycin once a day is harmful because it knocks out mTOR1 and mTOR2; but use once a week is safe because it only lowers mTOR1. The main obstacle is financial and not medical. Nobody has a financial incentive to promote rapamycin. But rapamycin could become more widespread, because Baby Boomers are very savvy and know how to use the internet to get information.

PDM: I note that of the drugs you advocate for anti-aging, metformin, aspirin, and ACE inhibitors/AR blockers are cheap, while rapamycin is more expensive. Does any other drug come close to rapamycin in efficacy or is it indispensable? Of the four drugs, what fraction of anti-aging effect is due to rapamycin in your estimation?

ASG: Rapamycin is only $3.50 for 1 mg if you buy it on line with a prescription from Canada; therefore monthly cost might come to $50-100 a month.

My rough guess of the relative value of each as anti-aging drug would be as follows: rapamycin, ACE inhibitor/AR blocker, metformin, aspirin: 75, 18, 6, 1.

PDM: Do you think that other, non-pharmacological anti-aging interventions, such as intermittent fasting or perhaps even intense exercise, are superfluous for someone on a drug regimen such as yours? If the drugs activate AMPK and inactivate mTOR, then would the physical interventions make any difference, given that they do that as well, and perhaps not as effectively?

ASG: I think physical activity is of great value. I cycled 1000K in May. I understand value of HIIT for people in their 40s; but for people my age, I think a few hours of exercise at moderate intensity is probably best. Humans are the premier long distance runners of the animal world. Running and walking can be too traumatic for joints in old people; but cycling is easy and safe as long as stay on bike paths and away from cars. The effect of using legs muscle at the cellular level is it increases AMPK which increases GLUT4 transport of sugar into muscle which reduces insulin resistance.

Caloric restriction is also of great value. Men should get their waist hip ratio down to 0.9 range. If you had a 32 inch waist when age 21, there is no reason you should not have a 32 inch waist line at age 75 and with rapamycin you can do it. After get rid of extra waistline fat; then I favor eating about 8% fewer calories than required; but without any additional weight loss

With all due respect to victims of the Holocaust, and not to minimize one of the greatest atrocities in human history, I cite the case of Yisrael Kristal. Yisrael is the oldest living man in the world and in good mental and physical health. In August 1944 at age 40 he went to Auschwitz concentration camp. In January 1945 he was rescued by the Russians and his weight was down to 80 pounds. He was probably just a few weeks away from death from starvation. He endured 6 months of starvation and hard labor. Only a small handful of men 40 years old were rescued from the Nazi concentration camps; so hard to say that mere coincidence that Yisrael Kristal is oldest living man in world. In a possible related study, mice fed rapamycin for 3 months in middle age went on to have a remarkable long extension of lifespan after rapamycin was stopped. The most senior mouse lived 1400 days which was stated to be the equivalent of 140 in human years. I mention this mouse study to show that what happened to Yisrael in 1944 could have an ongoing effect for the next 70 years.

PDM: Since I’m not a fan of statins myself, I note that you stopped taking one due to adverse side effects. What do you make of studies showing that higher total cholesterol is associated with longer life? Have you revised your opinion at all on whether it’s worthwhile to lower cholesterol or take a statin?

ASG:  I agree with your basic point that you don’t like surrogate markers. Lowering cholesterol doesn’t prove statins prevent heart attacks. However, I have seen studies showing statins lower all cause mortality. So I would use statins, if it did not cause problems for me.

PDM: You stated after following your anti-aging regimen for 14 months, “Subjective impression: Miraculous improvement in health; feeling old to feeling young.” I think that’s fantastic; why aren’t more people doing this? Do you know of any other physicians besides yourself that prescribe regimens like yours?

ASG: Anecdotal reports in medicine are always considered very unreliable and proving nothing. Aside from Blagosklonny, there are no anti-aging experts saying people should use rapamycin. If you showed my results to some anti-aging experts their response might be something like this: “Even taking all the results as true, it still proves nothing. It would require 30 years to show rapamycin increases lifespan or decreases age related disease and would need results in hundreds of persons for a statistical analysis. The results don’t even show rapamycin is a good fitness drug as subject also used diet and exercise which in themselves could account for all positive results.”

My interpretation is rapamycin is a miracle anti-aging drug; but some anti-aging experts would just poop-poop results as meaning nothing.

I know of no other physician who has a rapamycin based regimen like mine.

PDM: Did you have any trepidation about starting to take rapamycin, given that there’s so little human data on it for anti-aging?

ASG: I had great fear that rapamycin would not work. I wasn’t interested in something that would extend my lifespan. I wanted something that would reverse aging. I wanted to be restored to good health. I thought rapamycin based treatment might slow aging; but I never expected to feel young again. I consider aging to be the mother-of-all-disease; so while I certainly had fear, the fear was not about rapamycin.

I think one of the greatest days of my life was about 4 months into treatment when I suddenly had that “Holy shit” moment’ as in “Holy shit, this stuff actually works.”

When I say “Old” I mean you go for a walk in the park with your dogs and with a small hill you have angina, fatigue and shortness of breath and when I say “Young” I mean going for a 40 mile bike ride and feeling great.

PDM: Was your decision to take anti-aging drugs more or less sudden, i.e. did you give it any thought a few years earlier?

ASG: As soon as I had done enough research to know the score, there was no delay in starting treatment. I was very lucky in that by the year 2015 when I began my search for understanding of aging and treatment, there had been an explosion of scientific research and understanding of aging. By contrast, in the year 2005, nothing was known about aging, rapamycin, mTOR; it was all just gobbledygook.

From the start of research to the start of treatment was 8 months.

PDM: I was fascinated to learn about angiotensin disruption for anti-aging, which I’m not sure if I had heard of before, and also that it fits the growth vs longevity paradigm. (On second thought, I had heard of it, but I forgot. Must be the effects of age.) Do you think hypertension is a “normal” manifestation of aging and that everyone can expect to have it to some degree as they age?

ASG: The two best characterized systems which promote aging are the mTOR system and the angiotensin-renin system. Angiotensin II is the primary cause of hypertension; but angiotensin II also promotes atherosclerosis, damage to mitochondria and increase ROS in tissues. I think all older persons probably suffer from higher activity from angiotensin II than is healthy. So probably most old people had some degree of hypertension and they would benefit from being on angiotensin blocker/inhibitor (ARB/ACE). The important thing is to use one that crosses blood-brain barrier.

PDM: There exists a remarkable indirect correlation between insulin level and hypertension, heart disease, cancer, stroke, diabetes. What is relationship between insulin level and mTOR?

ASG: There is a direct correlation between insulin level and mTOR level in the cell. I believe that insulin level is the best surrogate test for mTOR level. So the chart showing very strong correlation between the 5 common diseases of aging and insulin level is not because insulin is bad per se; but that high insulin in blood indicates high mTOR activity in the cell.

PDM: Given that most of these drugs are cheap, and even generic rapamycin could come down in price, to what extent do you see major pharmaceutical companies as a hindrance to the adoption of this regimen? If they don’t promote it to physicians, since there isn’t enough money in it, will it catch on?

ASG: Our system is based on drugs being developed and promoted by Big Pharma. I don’t think Big Pharma is an obstacle; they just will not help. There is no way for anybody to make any money from rapamycin because it is a generic drug. So you are correct, very difficult for rapamycin to catch on.

PDM: Given that the use of these drugs could radically cut healthcare spending, do you see that as more of an obstacle, or an incentive, to its adoption?

ASG: Saving money is an incentive to the payors. It is not an incentive to the medical industry or to Big Pharma. So to be a real incentive need a different kind of health care system. You would need somebody in charge of entire system who could say need to save money by preventing diseases of aging and then that person would need the knowledge that such action was actually possible and then implement program to prevent diseases of aging.

In the system we now have, there is nobody to do that. There is nothing payors can do to implement preventive medicine and they certainly don’t know it is even possible.

I believe healthy old people could make a great contribution to society instead of being a financial burden. So the failure to have preventive of diseases of aging is a tragedy of the highest order.

PDM: Do you see any other interventions in your future or on the horizon? Or is your anti-aging regimen the current state of the art? Do you plan to keep practicing medicine indefinitely, now that you’ve solved your aging and health problems?

ASG: The future is here now. The focus on treatments of the future not yet available is a distraction from the very excellent treatments now available.

Blagosklonny provided the state of the art treatment in Koschei 2014 paper. In May 22, 2017 paper, “From rapalogs to anti-aging formula”, Blagosklonny updated treatment and I may include some of his new ideas in my office treatment plan.

I do plan to continue to practice medicine. Aging is an extraordinary complex disease and people should not be forced to fight aging on their own.

_________________________________________________

I thank Dr. Green for taking the time to answer my questions and for such a great interview. He’s a real pioneer in the application of anti-aging science to medical practice.

PS: Check out my Supplements Buying Guide for Men.

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80 Comments

  1. Jay Campbell says:

    Great interview and scoop Dennis. But this Doctor really has missed the most important point (his whole life actually). Building muscle tissue thru progressive resistance training would have solved all of his problems. He speaks about M-tor signaling and insulin resistance but none of these would be Issues if he would have been performing resistance training and building skeletal muscle mass over the course of his life.

    I have read most of the research about rapamycin and correlation does not equal causation. There is great risk at such heroic dosages regardless of Dr Green’s personal experience.

    The best anti-aging regimen is already defined by those us in the know.

    TRT+Insulin Controlled Living+Thyroid Optimization +Metformin +Resistance Training/Endurance Training = Optimized Life free of disease.

    It’s that simple.

    PS. I have a guinea pig starting Rapamycin next Monday. Expect a fully transparent report by Year end.

    • Natural Tasty Healthy says:

      looking forward to the Rapamycin report, Jay.

    • P. D. Mangan says:

      Hi Jay, thanks. You know I’m on board with muscle, and I agree that it likely could have solved some of Dr. Green’s health problems. It’s also not too late for him to start; if he were to ask me, weight training and dietary protein would be the number one thing I’d recommend, with the caveat that I don’t know anything about his diet. He notes in the interview that he does a lot of cycling, and while that’s good as far as increasing VO2max, it’s not going to do a lot for muscle.

      That being said, rapamycin certainly appears to have done remarkable things. N=1 of course, but someone has to be first – although rumor has it that Mikhail Blagosklonny, the rapamycin advocate, himself takes rapamycin.

      I look forward to hearing about your rapamycin guinea pig.

    • Allan Folz says:

      Literal or figurative?

      Speaking of, I recently came across that Bernese Mountain Dogs entry at Wikipedia. They are notoriously short-lived averaging 7-8 years, and succumb to cancer at a rate of nearly 50%, vs. 27% for other comparable breeds.

      Seems to me one would be hard-pressed to find a better figurative guinea pig for a long-term study on longevity treatments. Another reason I wished I’d bought that farm I’d always been thinking about. 🙂

  2. peter connor says:

    My question is–where in Canada can you get rapamycin with a prescription, specifically.

    • P. D. Mangan says:

      There are a number of Canadian pharmacies online.

      • Charles says:

        You can also buy it via Walmart with a prescription

        https://www.goodrx.com/rapamune?drug-name=rapamune

          • Bill says:

            Glad to be reminded of that PD. I wonder if the inhibiting process is dose specific ? That is would taking berberine twice a day, instead MTor more effectively ?

            Rampamycin here is harder to get : only by script and specifically for transplant patients…Other uses are off label and probably much more expensive.

          • P. D. Mangan says:

            Rapamycin is by scrip only here too, everywhere really. It’s impossible to say whether berberine or rapamycin would more effectively inhibit mTOR, though everything I know speaks in the favor of rapamycin.

          • Bill says:

            Rampamycin is only listed in Australia, for suppressing transplant rejection. …under its Australian brand name “Rapamune”, only for kidney transplant patients to provide immuno-suppression.
            https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-CMI-05267-3&d=2017061016114622483

            This link provides a lot of information about side effects . Some of them are fairly severe at the dosage recommended for preventing kidney transplant.

            It is listed under the Australian Pharmaceutical Benefits Scheme ( PBS ) so the cost of scripts to patients is capped at $38.00 A. for 100 tablets. A doctor here needs special ‘authority’ to issue a prescription for Rapamune.
            So much cheaper but much harder to access.

            Bringing it it in from overseas risks the parcel being confiscated by our quarantine inspection service ( AQIS ) who scan all parcels coming in the mail for illegal drugs.

            Hence my interest in Berberine. It is available as a supplement…Seem simpler somehow.

          • P. D. Mangan says:

            Here’s an item of interest, Bill. Metformin and aspirin synergize to activate AMPK. AMPK activation in turn inhibits mTOR. I see no reason why berberine and aspirin wouldn’t do the same. (I’m currently taking both.)

            True that some rapa side effects are severe at immunosuppressant doses, which is the whole point of weekly pulse dosing: few side effects, all the benefit. It’s a pity about the inability to get rapa; myself, I don’t feel quite old enough yet to feel I need it, but I plan to take it at some point, and I think my doctor, who’s an unusually open-minded fellow, may prescribe it to me.

          • Bill says:

            Good luck with that one PD ! But best I stay away from aspirin, what with the anemia I was diagnosed with last year after daily aspirin for years as an anti-aging supplement.

            Your comment about Metformin is appreciated. A source I was reading today about Berberine says that it also activates AMPK…and so presumably suppresses MTor as well…

            https://authoritynutrition.com/berberine-powerful-supplement/

            “one of the main actions of berberine is to activate an enzyme inside cells called AMP-activated protein kinase (AMPK) (5).
            This enzyme is sometimes referred to as a “metabolic master switch.”
            But to achieve this it suggests 1.5 grams in three does a day before meals. Not the one a day which I have been taking… Ummmm.

            So here I go with a sample size of just 1!
            🙂

          • Bill says:

            I misquoted the dose ! A total of 1.5 grams a day in three doses before meals..

            Long day active here and it’s sleep time for me.

          • Bill says:

            This hunch re Bernerine suppressing MTor, is confirmed here :
            https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-015-0450-z

          • There have been a great many different comments; but everybody has been in general agreement, which is that aging is a disease, a very bad disease and people should fight aging. This basic attitude is in stark contrast to traditional medicine which aging as a natural process, not a disease and not something that requires treatment. It is the attitude that aging doesn’t require any treatment, rather than the lack of effective treatment, which is the main problem. It is very good that everybody here is looking for ways to fight aging

          • Bill says:

            Dr Allan, in my experience it’s a rare GP who will ever consider aging as a ‘disease’.

            I have been seeing my GP since 2000. He is cheery, competent and professional in a normal GP sense but I am educating him about how to prevent aging. Queer thing is he is in his late fifties and aging is having an ‘impact’ on him personally. So checking out aging as a disease is completely to his own advantage.

            Folks is odd often !

          • alan green m.d. says:

            Hi Bill,

            From the dawn of man until 2006, nobody had a clue what aging was, so very easy to say aging not a disease. That all changed in 2006 with Blagosklonny paper, (Immortality and quasi-program) and suddenly aging had a defined cause and a defined treatment (at least for one aging disease); so after 2006 not thinking aging is a disease is just ignorance. However, Darwin explained evolution in 1859 and half of Americans don’t believe in evolution; so ignorance is very resistance to science.

          • Rick says:

            Dr Green I have been on a course of cyclosporin for my psoriasis and I wonder if it has any similarity to rapamycin?

      • Charles says:

        This appears to be a place to get it without a script. Don’t know anything else about the company and I’ve never tried it.

        Per their e-mail to me

        Hi dear and thank you for inquiry. All in stock and ready for next-day dispatching. We can offer you Rapamycin 1mg × 50 pills = 3$ per pill.

        Ems express shipping takes approximately 7-10 days up to your hands and it is 25$ extra.

        We can accept payment through Moneygram or through wire transfer officially through invoice. 

        https://www.dropshipmd.com/buy/rapacan/

        • van says:

          I have ordered from dropshipmd.com twice. 300 mg Sirolimus $1.75 mg. Free shipping, but must do a wire transfer from your bank to theirs . No Pay pal or credit cards. My cost was $25. You must buy in volume in order to get price down. They are very good, but takes 4-5 weeks. I also ordered 550 Metformin SR 1000 mg for $100.

        • Lawrence says:

          I have some on the way , shipping confirmed. Excited!!

      • David Andrews says:

        Yes, but you need a PRESCRIPTION! And how many doctors are willing to give you one? It’s not fair to tease us with this breakthrough when it is very difficult to obtain.

        • P. D. Mangan says:

          Indeed, David, but i predict the number of willing doctors will increase, and with a bit of looking around, you might find one now. Or you could always fly to New York and see Dr. Green.

        • Allan Folz says:

          Are you being facetious? Should Dennis just sit on info because, well, it’s too hard for some folks to put into practice?

  3. Charles says:

    I have an appointment with the good doctor in July – should be most ineteresting.

    From his website

    In anti-aging medicine, Blagosklonny  recommends intermittent or pulse and also suggested weekly. Rapamycin has a half-life of @ 62 hours. That means daily use is once every 0.4 half-lives while weekly use is once every 2.7 half lives. For that reason, only data regarding using rapamycin once a week is applicable to side-effects expected from once a week use and daily side-effects are not applicable. 

    In my practice, I consider the proper anti-aging dose of rapamycin to be 2-6 mg and the proper interval 1-3 weeks. So the most conservative anti-aging dose would be 2 mg once every 3 weeks.

    So – @ $3.50/pill the is not that great.

    • Allan Folz says:

      I remember reading that from his web site here recently and thinking, “wow, he kind of just gave away the store.”

      I also read somewhere recently an intriguing suggestion that a once or twice a year rapamycin schedule (I think, it might have been something else though, but the idea stands) to knock-out senescent cells before they get a chance to proliferate would be an incredible preventative.

      As I keep writing: an ounce of prevention beats a pound of cure.

      The thing is, I feel like lots of this stuff is still in the ‘Flowers for Algernon’ stage for anyone south of 60, at least. Even to start one’s own N=1 (or 10) studies on dogs, you wouldn’t get satisfactory results for another 15 years, and well, by then, I’m no longer too young to worry about starting too early. And I don’t exactly have room for 1, much less 10, dogs at my present domicile. So there’s that too.

      • P. D. Mangan says:

        Re giving away the store, it wouldn’t seem to make a lot of difference if no other doctors will prescribe rapamycin. (Metformin is rather easier to get.) I also wonder about the value of it for someone my age (early 60s) as I honestly don’t feel old. OTOH, feeling like I was 18 wouldn’t be bad either.

      • alan green m.d. says:

        Reply to Allan Folz comment about senescent cells.
        Senescent cells do not proliferate, they just get bigger and make bad substances that promote disease.
        The twice a year treatment was not about rapamycin. It was about an imaginary drug that would remove senescent cells. The idea was that this imaginary drug would be given once or twice a year and would zap all the senescent cells. Check back in 25 years to find out if drug still imaginary.

    • P. D. Mangan says:

      Charles – yes, should be most interesting. At $3.50 a pill, using the dosing range above, cost could be quite low (2 mg every 3 weeks) or much higher, say about $80 to $100 a month at the aggressive doe.

      • Dean says:

        Here in 2019. Life Extension Foundation, has their Senolytic Activator that is quite reasonable wrt pricing. It is once-a-week ingestion of 2 capsules. I take it and other life extending herbs like goji berries, jioagulan, astragalus, Lion’s Mane, ashwagandha, ginsengs (American and Asian), methylene blue (Mitoblue), vinpocetine, macuna dopa, PQQ, chaga, etc. Also Carbon 60, high dose C, HMB,maganese L-threonate, etc.

        • Gavril says:

          I’ve already done a three rounds of Fisetin. I weigh 90 kilos, so the Mayo clinic study would put my dosage at 180mg * 2 days. I take 3 grams, two days in a row, then repeated three months later. When I do this, my mind seems to wake up and lose any brain fog. I’ve also done a round of Azithromycin, based on its senolytic properties, and hopefully got the serum level correct. I’ve also done my first round of dasatinib and quercetin. Too early to say if that has had any salubrious effects. I’ve been taking Met/Telmisartan/statin for years. I took my first 5mg of Rapa last Saturday. (Assuming my scales were correct). I felt a bit lousy over the past several days, and my allergies have been worse than usual. I suppose that’s to be expected if my immune system is getting kicked into gear. I also take a normal dose of Tadalafil for my prostate, which has pretty much stabilized, and I can usually sleep through the night without having to visit the toilet more than once. I used to have to go every hour on the hour. Oh, let’s see, One last thing: Selegiline, 5mg per day. Look it up. My dad had Parkinson’s, diabetes, quintuple bypass, you name it. He died of prostate cancer, so I keep a close eye on my PSA, and eat my tomato sauce and cruciferous veggies. Mom died of a stroke at 56, so I make sure to control my BP, which has been high for 30 years.

          At 65, I don’t have time to wait for studies. I do weight training three times a week and walk whenever I feel like it, but probably should do more. My much younger wife keeps me motivated by drooling over my 6-pack. My PT is using my photos for advertising on his web-site. I still am nowhere close to retiring, and have no plans to ever do so, especially with 12-year-old twins still at home.

          But here’s the thing: I don’t necessarily FEEL all that great. I don’t feel any particular motivation to get out an do anything. And yet, I am quite active, recently took my daughter across Eastern Europe by motorcycle in every kind of weather. My body does everything I call upon it to do. And when I observe myself doing the things that I can do, 60 pushups, 150 crunches, I guess I just need to remind myself that, yes, I guess I do feel pretty good.

  4. Bill says:

    PD Wow ! Thank you & Dr Green for this interview. It really does put things into perspective.

    My only query is about this photo : Is it a before or after shot ? If Rampamycin can provide good healthy non aging, great ! But good looks would be an added bonus : -)

  5. JP says:

    Is it realistic to think a doctor would prescribe an immunosuppressant if you promised to take it only once a week? Basically you are asking the doc to cooperate in allowing you to experiment on yourself. I can see doctors shying away from that for liability reasons.

  6. Rapamycin has a single action which is to block mTOR. So the natural use of rapamycin is to treat diseases caused by too high mTOR. In this regard it is similar to treating a disease like hyperthyroidism by lowering production of thyroid hormone. Of course proper level of thyroid hormone is essential and proper level of mTOR is essential. Calling rapamycin an immunosupressant is naming it by a side-effect produced at toxic doses. In low dose rapamyin improves immune function in older persons. Rapamycin should really be called an antifungal agent as it was designed and produced and initially used as anti-fungal agent. However, because it blocks the command and control of the cell, it has potentially innumerable other uses. One possible use is to poison the immune system as used in transplant medicine and another use is to ameliorate the disease called aging. Comments on rapamycin should read in conjunction with Dennis Mangan couch potato story about age-related disease and insulin resistance. In that paper middle age persons were followed for 6 years. People were divided into 3 groups of high, medium and low insulin resistance. The end points were heart disease, cancer, stroke, diabetes and hypertension. All disease was in the 2 groups with high insulin resistance and the group with insulin sensitivity did not develop any disease. According to mTOR theory of disease, insulin resistance caused increased levels of insulin, high levels of insulin causes high levels of mTOR and high levels of mTOR caused diseases of aging. If you do not believe the disease called aging is caused by high levels of mTOR, then of course, you do not believe rapamycin which only lowers mTOR ameliorates aging. The most important thing everybody show know about rapamycin is less is more. Low weekly dose is good and high daily dose is poison.

    • Allan Folz says:

      Greetings Dr. Green,

      Thank you for this very thorough interview Q&A with Dennis.

      Your comment here really pulled it all together for me. It suggests that, like insulin, there might be a marker for mTOR activity. I’m guessing this is all too new for there to be such a diagnostic, but is there any research in that direction?

      It seems to me there ought to be an optimal level of mTOR activity which balances immune system function against deleterious effects of aging. It also suggests that one might wish to cycle it, perhaps periods of exceptionally low mTOR activity for regenerative effects, high mTOR activity for fighting illness (or athletic competition?), and some standing-by baseline, which is apparently lower than our body’s natural endogenous level.

      Has this been a consideration by anyone for research? If so, have they any results in that regard?

      Best Regards,
      Allan

      • P. D. Mangan says:

        Allan, good question, which I’ll second. My own tentative answer (not that you asked me) is that transient mTOR deactivation is indeed beneficial. Some studies have reported that a single course of rapamycin for maybe a few months extends lifespan.

        • Response to Allan Folz question:
          The question has very many assumptions which I do not believe are true:
          1.Immune function: Dec 25/2014 study by Mannick showed DECREASE of mTOR by rapalog in elderly improved immune function.
          2,Exceptionally low mTOR would be good for regeneration: No reason to believe that is true.
          3, High mTOR activity good for fighting illness or athletic competition; no reason believe that is true
          According to mTOR theory by Blagosklonny, mTOR in older persons is quasi-program. This means mTOR is program for growth and development ages birth to 25. (call that mTOR 1.0).In older persons still running on mTOR 1.0 only that is bad program. All the cells need an update (mTOR 2.0 for old people). The problem is no way to install new program mTOR 2.0, There is a level of mTOR that is best; but no way to measure that level. General idea is mTOR too high in older persons and if reduce mTOR to healthy level, then would slow aging and diseases of aging.
          The part of your question I disagree with is that immune function, regeneration and fighting infection and athletic competition all require different levels and some need higher level and some need lower level. The proper level of mTOR should be something not too high or too low.
          The great confusion is to try and go from effects in transplant medicine when mTOR used as a poison to knock out immune system and then apply those findings to use in anti-aging medicine. It is probably best to think of them as two different drugs. One is used to continuous reduce mTOR1 and stop action mTOR2; while in anti-aging idea just to partially lower mTOR1 and not touch mTOR2. The very name of rapamycin as immunosuppressant is false. Only high dose rapamycin is immunosuppressant while low intermittent dose improves immune function in older persons.
          In response to first part of question; insulin level is best indicator of mTOR level. High insulin level means high mTOR activity and low insulin level means low mTOR activity in cells (unless insulin low due to destruction of Beta cells.

          • Allan Folz says:

            Thank you for the reply. Very interesting. Very thought-provoking.

            Sounds like mTOR as a black-box model is analogous to iron/ferritin, which has been well-covered by Dennis. To wit, while you can certainly overdo it, moderate phlebotomy and moderate consumption of iron chelators seem to have only positive consequences.

  7. Tom says:

    Gee a Doctor recommending a drug? That’s a new concept. I Take Longevinex a resveratrol capsule eat a very clean diet and at 69 could pass for his son.

    • P. D. Mangan says:

      That’s great. I take resveratrol too, but it hasn’t extended lifespan in mammals, and rapamycin has.

      • Tom says:

        P.D. I have been studying this molecule since 2003. Resveratrol is resveratrol. Longevinex is Longevinex. In a 12-week rodent study CR activated 198 genes while resveratrol as a molecular mimetic of CR activated 125 genes, whereas Longevinex significantly differentiated 1711 genes. If rodents are placed on life-long CR 831 genes are significantly differentiated (expressed or silenced); Longevinex differentiated 677 (82%) of those 831 longevity genes, representing the closest thing we have to CR reported to date. While no longevity science is conclusive beyond calorie restriction, that doesn’t mean we can’t use the best available science. This is the first generation of people that can consciously attempt to live longer and healthier utilizing epigenetics. Epigenetics trumps genetics. We hear of reports of people taking Longevinex whose inherited color blindness vanished. This is an anecdotal example, though there have been numerous reports. Resveratrol is a weak mTOR inhibitor. Many of the animal studies have utilized pro-oxidant mega-dose resveratrol which negates its hormetic effect. The scientific community appears to have intentionally taken resveratrol and over-dosed it to side track this wonder molecule. Rapamycin (Sirolimus) is a problematic drug that dampens the immune response, but taken in a very low dose may turn on the Nrf2 gene transcription factor to activate internal antioxidant enzymes (glutathione, SOD, catalase). The trick is the low dose. Longevinex is the only resveratrol-based product that has undergone dosing and toxicity testing. It utilizes molecular synergism to produce beneficial effects. There are astonishing reports of people taking Longevinex who had undergone multiple heart attacks with no damage to the heart, who have come back from blindness, even a man who recovered his memory 30 years after brain trauma. I can’t tell you how many report better vision taking Longevinex. An eye researcher says they have now visualized regeneration of the retinal pigment epithelium at the back of the eye with Longevinex use and that this represents unprecedented stem cell regeneration. Re-think resveratrol. — Just for the record I have no financial interest in this company I just LOVE the way I feel at 69. T

        • P. D. Mangan says:

          Also great. Longevinex has, besides resveratrol, vitamin D, IP6, cholorogenic acid, and green tea extract. I get all that too in my cheap anti-aging supplements. As for rapamycin, it of course has side effects, but pulse dosing appears to mitigate most of them, and pulse dosing has extended the life of lab animals. Anyway, as for living longer, you’re preaching to the choir here.

          • Tom says:

            Same here P.D. Dr. Green feels better on Rapamycin I feel great on Longevinex. As far as family my mothers mother died at 57 of heart disease her father at 69 (my age) of heart disease my father died at 60 of heart disease and a few cousins died in mid 50’s of heart disease. My mom who has been taking Longevinex since 2004 is now 94. I love calling her and telling her jokes, she always gets them.

          • P. D. Mangan says:

            Of my grandparents, 3 died of heart disease. My father had heart disease for decades that impaired his quality of life greatly, although it was cancer that got him in the end at age 87. My mother is 95 and takes a number of supplements that I got for her.

          • Rick says:

            The research of Dr Pierpaoli also has shown a dramatic life extension of mice using melatonin supplementation. I wonder if melatonin affects mTOR?

        • Ole says:

          Tom, what about the loss of athletic/aerboic performance while taking Longevinex? Decline in VO2MAX is certainly the least thing on my wishlist…

          • Tom says:

            Ole go here and check this my own experience bears this out my atheletic/aerboic performance is through the roof I can do virtually any kind of physical activity I want .
            https://www.resveratrolnews.com//?s=exercise&x=0&y=0

          • Ole says:

            Thanks Tom! I’ll check it out. In the end it’s my own N=1 experience that really matters.

          • Tom says:

            Of course Ole, I can only say how I feel at 69 and what I can do and I am amazed, never thought I would be able to do all this at this age. The brain is older and wiser and the body is young and full of juice. I’m loving it.

  8. Brandon says:

    Dennis, don’t want to rain on anyone’s parade here, but was just researching how it might be possible that metformin is associated with >50% increased risk of Alzheimer’s as per a new study out of Taiwan, and came across this:

    “…brain damage in Alzheimer’s disease is linked to the overactivation of an enzyme called AMPK.”

    https://www.scripps.edu/news/press/2013/20130410polleux.html

    There is a thread on longecity that talks about this issue as well:
    https://www.longecity.org/forum/topic/84811-does-metformin-wo-b12-deficiency-andor-ampk-activation-in-general-cause-alzheimers/

    I’m not an expert in this area, but this would seem to be a cause for concern I would think.

  9. L says:

    I’ve been taking 2-3 mg of Sirolimus with grapefruit juice since late January. I’m in my late 50’s and cycle hard and lift weights moderately 2-3 times a week. I was very healthy before dosing and have had no health issues since I started dosing, ie no colds, flu etc. I was taking 2 mg a week but now I’m dosing 3 mg every other week. Only adverse side effects were a couple mouth sores when I started but none in the last 3 months. Good effects? Nothing earth shattering. I’m working 60 to 70 hours a week for the last 2 months but I have kept up my fitness some how. I can beat all my ride buddies in my age group and most people younger then me. My power numbers are backing up those observations. So I guess you can say it is keeping me “younger” but it still could all be a placebo. There are a number of people taking Rapa and we will know more about our combined experiences in the future.I’m very optimistic. I have not seen Dr. Green, just self experimenting.

  10. Herman Rutner says:

    Thesis possibly relevant to intense exercise including weight lifting?
    “Markers of immunosenescence and oxidative stress in healthy adults
    Turner, James Edward (2011)
    Ph.D. thesis, University of Birmingham
    Download — Preview
    Turner11PhD.pdf
    PDF (2781Kb)
    “Abstract: This thesis investigated markers of oxidative stress and immunosenescence in healthy adults. The results presented represent several novel findings which support the notion that oxidative stress and infection with micro-organisms shape our biology and can accelerate aspects of ageing. Acute exercise of high intensity was shown to cause alterations in the cellular composition of blood, which was most pronounced in lymphocyte sub-populations important for immunosurveillance. This exercise also resulted in increased markers of oxidative stress in lymphocytes, and resulted in a whole body oxidative stress, which was more pronounced and prolonged, following ultra-endurance exercise. Studies also showed that infection with a highly prevalent and asymptomatic herpes virus, Cytomegalovirus (CMV), shapes our immune biology in two significant ways. First, CMV amplified the magnitude and kinetics of lymphocyte responses to exercise, which could potentially facilitate immune surveillance, or aggravate inflammatory processes. Second, CMV was seen to drive the development of an ‘Immune Risk Profile’ in young adults, characterised by increased inflammatory activity and smaller responses to vaccination. These outcomes are associated with frailty, cognitive decline, and mortality in the elderly.”.
    Rapamycin has numerous side effects even at low oral maintenance doses. Monolaurin may be a safer choice for preventing immunosenescence by inhibiting antibody overloads from subclinical infections from enveloped viruses like EBV, HIV and especially CMV also prevalent in younger folk, possibly also leading to life extension and/or improved quality of life. Testing for plasma levels of CMV, pre and post monolaurin, may be worth doing.

  11. Ole says:

    Herman, monolaurin seems like a safe choice for preventing immunosenescence, but what has it got to do with mTor inhibtion??

  12. Grapefruit juice inhibits metabolism of rapamycin. Inhibiting metabolism of any drug increases risk of side-effects. This is especially true for rapamycin in which metabolism to low level is essential to make weekly rapamycin safe compared to daily rapamycin. Anybody taking rapamycin should be warned to not drink grapefruit juice.

    • lawrence rosen says:

      Question: would grapefruit juice taken with rapamycin serve to reduce the optimal dosage to reduce cost. For example, would taking 1 gm of Rapamycin and one glass of gfj equal 3-4 mg of Rapamycin taken alone?

  13. oil boy says:

    Is there an age that would be too early to start?

    • Hi oil boy, A few people have started in 40s with very low intermittent dose. I would certainly think anything before 40 too soon. However, if somebody at very high risk for Alzheimer’s disease, say double ApoE4 carrier, then age 35 would make sense. Somebody at 300 pounds at age 35, rapamycin would be good idea.

  14. Geoffrey Roth says:

    Where can I get rapamycin

  15. DELL VANN says:

    According to the late Dr. Denham Harman, (the scientist who developed the free-radical theory of aging), I am the only person in the world who has consume ethoxyquin (a FDA perservative) for 40+ years. Ethoxyquin was one of the five substances that Dr. Harman used to prove his free radical theory of aging.

    It must be having some type effect on me because the people that I went to high school with, look more like my parents than my class mates and my energy level is that of a 30 year old for a 70 years old man.

    I’ve always been amazed how ethoxyquin has been absence in interest in human research studies.

    DELL VANN

  16. Dennis Fink says:

    Thanks much PD and Dr. Green for the great interviews and discussion! Love your “Supplements” book PD and am on my second round of Sirolimus based on Dr. Green’s great work! At age 73 I didn’t notice the huge benefit that Dr. Green saw but after 40 years of AFib, (the arrhythmia made me more health conscious) I still noticed some improvement and hope to see more over the coming 3 months. I was using grapefruit juice to decrease my dose from 6 mg/wk to 3 mg but I may change that after Dr. Green’s caution, although I didn’t notice any side effects.

    • P. D. Mangan says:

      Hey Dennis, that’s great. Please check back in after you’ve been taking your sirolimus (rapamycin) for awhile and let us know how things are going.

  17. Dennis Fink says:

    I think I’ll go this route w/ the grapefruit juice/rapamycin to save some money! https://www.scientificamerican.com/article/grapefruit-juice-improves/

  18. Ahmed Shahab says:

    Have you all heard about a nutritional supplement which replanishes microcirculation at the end organ level so what we see is what we believe which is not the case it the internal organs and their aging which we can only check through investigations microcirculation increases oxygenation transportation of nutrients and removal of toxins from areas where the microcirculation was decreased or diminished if the microcirculation of any part or the whole body can be brought back to normal the purpose is achived like in Diabeties diabetic ulcers develop in uncontrolled DM eventually gangrene leading to amputation so if we can resolve the microcirculation problem then i suppose we are on the right track. Antiaging.

  19. DID RAPAMYCIN HAVE AN EFFECT ON REVERSING GRAY HAIR TO ITS NATURAL COLOR AND DID IT REVERSE BALDING?

  20. Linda Speer-Luck, PhD says:

    Dr. Green is also a very kind and altruistic human being. He recently spent two hours reviewing lab results, explaining the entire Rapamycin protocol, etc when I saw him recently. A treasure.

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