As the cruise ship sailed from Iceland to Canada I started working on a blog about rapamycin. When I came across Dr. Alan Green’s website I got badly sidetracked, for Dr. Green has recently specialized in being a doctor of rapamycin. Partly because of the benefits he got from taking it himself. He is located in New York city and when I realized that I contacted him about an appointment for the day we docked there. With the short notice (5 days), and especially the fact it was a Sunday, I had my doubts it would work. My pessimism was misplaced, for he was kind enough to agree to meet with me at 2 pm.
Mostly I wanted to visit Dr. Green to see what he thought about rapamycin and to see what was required to get a prescription for it.
In the US doctors are allowed to prescribe proven drugs like rapamycin for off-target use. This means it is legal for Dr. Green to give me a prescription for a drug more commonly used to prevent rejection of transplanted organs. Rapamycin prevents organ rejection is by slowing cellular turnover, which reduced immune system activity. It slows turnover by reducing the activity of the cell’s mTOR pathway [https://en.wikipedia.org/wiki/MTOR]. This is a key cellular nutrient and energy sensing network node, and by reducing mTOR rapamycin slows the cell’s activities. Use enough rapamycin and the result this is a depressed immune system, hence lowering the risk of rejection for transplant recipients.
Take a little less rapamycin and you don’t depress the immune system quite so much, yet gain many of the longevity advantages of mTOR suppression. Your cells start “behaving” in a better fashion and, “believing” they are under nutrient stress, they start cleaning up accumulated junk proteins and other detritus that collects in aging cells. Especially those cells with too many sugars and a higher than desirable energy supply. Rapamycin still depresses your immune system a bit, so caution needs to be taken with infections, and slows the turnover of your intestinal lining. I suspect quite a few other things happen as well that are not well studied or understood yet. As science figures out how mTOR interacts with the cellular control networks we will learn a lot more about how rapamycin affects aging. This may result in additional drug targets. But for now, prolonged calorie restriction is the best way to affect mTOR to extend a healthy life, and if you can’t manage calorie restriction rapamycin is the best drug to accomplish nearly the same results.
The cruise ship docked on time and we were scheduled to clear customs at 11:30. This would have given me a decent margin to get across New York City from Pier 88 to his office by 2. Unfortunately, customs officials were delayed getting to us because they had to process a ship with 5,000 passengers before they could clear our “measly” 2,000 passengers, so I was an hour late getting off the ship. I sent Dr. Green a text telling him I would be late and then hired a cab to take me to the subway, which appeared to be the quickest way to his office. At the end of the subway I took another cab the remaining few miles. I was about 20 minutes late arriving, but luckily Dr. Green was very accommodating.
His was a brown house located in a quiet subdivision with well-kept yards and friendly neighbors (I found this out when I left; I trespassed on a yard to get a photo of a sign and the owner came out and we chatted for a few minutes; later a lady sat by me to wait for the train and she was very nice, telling me about the neighborhood) Dr. Green turned out to be a wiry man who appeared to be about 65 and in great health. I later found he is closer to 75. He credits his weekly consumption of rapamycin for his good health.
In 2003 the Interventions Testing Program was started to test drugs for their effect on mouse aging. As a result of this program, rapamycin was discovered to be a drug that significantly slowed aging in mice. By 2014 there was a lot of proof rapamycin was a means to slow aging in most animals and Dr. Green became interested in the drug for himself. After doing his due diligence (which, for him, meant fully researching the drug and its effects and contraindications). Then, starting in 2016, Dr. Green started taking a weekly dose of rapamycin. His results were visible when I visited him; he did not look his age.
The drug was very successful for him, reducing his weight to his ideal target, improving his health, stamina and reducing the many diseases of aging he felt were beginning to impact his lifestyle. This success convinced Dr. Green his own patients could benefit from using rapamycin. Of course, he is careful to tell his patients that it is a drug that is not proven to do what the science indicates: Extend healthy lifespan. Especially in people. For any given individual the results may not be as stellar as they were for him. As this tale unfolded, Dr. Green pulled out study after study to bolster his statements. By the time I left I had a stack of reading an inch thick! All his references are listed below. He has concluded that rapamycin was not only safe enough for him to use, but that it should be taken weekly by everyone over the age of 50!
Then he proceeded to my medical exam. Primarily he asked questions about my general health to make sure I didn’t have any contraindications like being susceptible to bacteria. Then he took my weight, height and blood pressure. He also measured my waist and hips, commenting that my waist to hip ratio was good (even though my overall weight is not), indicating my fat to muscle ratio is not as bad as I had feared. He also asked if I knew my fasting insulin and fasting glucose levels. While I hadn’t brought them with me, I did have them on my computer so I promised to email them to him. He pointed me to a website I could use to check them myself if I wanted. This website is published by The Blood Code, and is a handy calculator for determining your insulin sensitivity [https://www.thebloodcode.com/homa-ir-calculator/].
I mentioned my regular fasting and Dr. Green pointed out that my fasting 36 hours once a week was already impacted mTOR in a positive fashion. He suggested I take rapamycin only early enough in my week so the level of the drug would be greatly reduced when I took did my fast. In other words, take rapamycin a day or two after my weekly fast. This would (hopefully) prevent much interaction between my fasting and rapamycin. If I didn’t do this there could too much interaction between fasting and rapamycin and it could depress my immune system a bit too far, increasing my susceptibility of getting bacterial infections (and other problems). If I had the willpower, I could just do full time calorie restriction instead of taking rapamycin, but I have never managed to stick to a 1/3 reduction in the number of calories I eat–at least not for any length of time.
Weekly rapamycin, like what Dr. Green recommends, improves your immune system handling of viral diseases, but it also depresses the innate immune system. This can lead to bacterial infections. Of the 300+ patients Dr. Green has, only 2 have had problems with this. Quick application of antibiotics if you get sick is necessary, he recommends having antibiotics handy–it could be dangerous to have to take the time to go to a doctor, convince the doctor it was serious enough to warrant antibiotics and have them filled. I had no contra-indications for taking rapamycin, so Dr. Green issued me 2 prescriptions; one for rapamycin and one for an antibiotic in case I got sick; he said just assume I have a bacterial infection if my temperature went over 100 and take the antibiotics.
Then our discussion went off in other directions; we talked about GDF-11 (which some people are taking to combat aging–I think foolishly because the proof is not there yet), senolytics of which Dr. Green recommends fisetin but not the senolyic pair Dasatinib and quercetin. We also talked about blood transfusion of cord plasma (some people buy cord blood plasma, collected from the previously discarded placenta, to extend lifespan) which Dr. Green is very much against. He pulled out a couple of papers he had about senolytics and suggested I think of fisetin. I suggested eating several pounds of strawberries a day, which are rich in fisetin, rather than taking it as a pill. We agreed that this might be an interesting way to get enough fisetin to act as a senolytic. In the US some senolytics are not considered as prescription drugs because they are normally found in food, so it is up to me as to whether I should take them or not.
Before I left I asked Dr. Green if he would be willing to be in my network of people for suggesting health and lifestyle choices to my readers, and he said he would be very happy do so. This will fill a key gap in my resources, for he is the first medical practitioner who has joined with any experience with rapamycin. I think he will make a great resource, not only for my blog but for my readers!
As I walked to the train station, I pondered the mountain of information Dr. Green had given me. One issue science today has is the sheer volume of information available, and how to sort out what is good and what isn’t. On the train back to the ship I looked through the information Dr. Green provided, I saw he had found the key information for the benefits of taking rapamycin for me. All I had to do was read it! The general information is already available on his website; what he gave me was the science behind that information. I was eager to read it and see if I agreed with his conclusion that rapamycin is an effective approach for slowing and even reversing some aspects of aging.
Many aging interventions need to start when a person is young. My son, who is almost 18, has been muttering about doing calorie restriction. This is the gold standard intervention, well proven in worms, mice, monkeys and many other animals. It has not been proven in humans, though there is a lot of data showing that it works (it reduces blood pressure for example). But this intervention requires you to start early to have the best effect. Rapamycin has a huge advantage in that you can start later in life and still derive most of the life extension you would gain by starting early. In mice some reports have suggested gains of 20% of total lifespan, nearly doubling their remaining lifespan. Whether this will work in humans remains to be seen. But if so an average guy of 58, expecting to survive to 78, would live to 93! Mice, however, are kept in jail (cages) in closely controlled environments and people are “in the wild”, so their environment (mostly due to exposure to bacteria) may not be good for using rapamycin in. Senolytics have an advantage over this, in that they also act on the old but do not have problems for the immune system. Unfortunately, they are not well enough studied to determine other possible impacts.
I think it would be really interesting to do a follow-up study and see how all Dr. Green’s patients are doing; a more long-term study would really show how well rapamycin works as a means to extend lifespan. Perhaps I can come up with the money to do a follow-up study, if Dr. Green’s patients would be willing! Such a study would require years to implement, for to really test life span extension in humans requires at least a 20-year study–and if rapamycin adds 15 years onto the average patient’s life then to really complete it would need 35 years! But you can get a good indication in a few years by using the new biomarkers of aging that are being developed.
The cruise ship left New York nearly 10 days ago and is approaching Ecuador. I have just managed to review the research reports Dr. Green presented to me. The conclusions in the reports he gave me look sound. Next, to complete my own due diligence, I must finish the research I started when I got sidetracked by the friendly Dr. Green. But now I have prescriptions so if I decide medication is a route I want to follow, I can do it. Come back later and I will update this blog when I finish my research. I hope by Christmas time, for if I am going to take rapamycin I would like to start it in the last half of the winter to reduce the odds of my getting sick–late winter in Alaska there are very few bacteria so my depressed immune system is unlikely to be challenged.
In the meantime, Dr. Green’s website [https://rapamycintherapy.com] covers a lot of what I was going to say about rapamycin, so I recommend you visit it and see what you think for yourself. Eventually I will write a blog about the darker side of taking rapamycin (reduced gut function because of lower cellular turnover; poor immune response and anything else I come across). Just be aware that rapamycin is not a drug approved for extending lifespan and it may not be a good choice for you.
References provided by Dr. Alan Green
Can a Single Pill Keep You Healthy to 100?
By Sari Harrar. AARP (https://www.aarp.org). July 1, 2019
General interest article.
Does rapamycin slow down time?
By Mikhail Blagosklonny. Oncotarget 2018 Jul 13.
Rejuvenating immunity: “anti-aging drug today” eight years later
By Mikhail Blagosklonny. Oncotarget 2015 Feb 16.
Disease or not, aging is easily treatable
By Mikhail Blagosklonny. Aging: Open-access impact journal on Aging, 2018 Nov 17
From rapalogs to anti-aging formula
By Mikhail Blagosklonny. Oncotarget, 2017 May 22.
Koschei the immortal and anti-aging drugs
By Mikhail Blagosklonny. Cell Death & Disease, 2014, Dec 4.
TOR-driven aging: Speeding car without brakes
By Mikhail Blagosklonny. Cell Cycle, 2009 Dec 15.
Aging and Immortality: Quasi-programmed Senescence and Its Pharmacologic Inhibition
By Mikhail Blagosklonny. Cell Cycle, 2006 Sep 15.
mTOR inhibition improves immune function in the elderly
By Joan Mannick, et al. Immunology, 2014 Dec 24.
Researchers discover how to slow aging
By University of Minnesota. https://medicalxpress.com/news/2018-10-aging.html, 2018 Oct.
Fisetin is a senotherapeutic that extends health and livespan
By Matthew Yousefzadeh. EBioMedicine, 2018 Sep 29.
mTOR, glycotoxins and the parallel universe
By Alan S. Green. Aging, 2018 Dec 12.
Advanced Glycation End Products in Foods and a Practical Guide to Their Reduction in the Diet
By Jamie Uribarri et al. Journal of the American Diet Association, 2010 Jun.
Rapamycin retards epigenetic ageing of keratinocytes independently of its effects on replicative senescence, proliferation and differentiation
Horvath et al. Aging, 2019 May 26.
Rapamycin retards epigenetic ageing of keratinocytes
By University of Minnesota. https://medicalxpress.com/news/2019-06-rapamycin-retards-epigenetic-ageing-keratinocytes.html
Chronic Supplementation With a Mitochondrial Antioxidant (MitoQ) Improves Vascular Function in Healthy Older Adults
By M. J. Rossman et al. Hypertension, 2018 Jun.