Rapamycin self-experimentation
I've just begun a 10 week self-experimentation with RapaPro rapamycin. I'll be taking 5 mg once a week, which is roughly the dose that Dr. Alan Green recommends on the high side and seems to be about what Dr. Attia supports/recommends.
I'm a 48-year-old male in generally excellent health. I've been following longevity science for a decade now and in the last couple of years have gotten more serious about it and also in trying new things that seem to have good data to back them up. I've been taking NR for a couple of years, as well as resveratrol and phosphatidyl choline.
After my first dose a couple of days ago I had some mild body euphoria that seemed to result from reduced inflammation. I felt less creaky overall and hummed with pleasure. I'm not measuring any biomarkers quantitatively, but will report my results in terms of reduced cold symptoms (I've had a mild sniffle for months now due, I think, to an ongoing tooth infection and the fact that I work out pretty hard a few times a week, leaving less bodily resources to kick my sniffles), increased/decreased energy, feeling of wellbeing, etc.
Dr. Green convinced me that there is real potential here when he talks about going from feeling very old at 70, unable to even walk his dog without suffering, to biking 40 miles and feeling great after.
I'd be curious to hear others' experience with rapamycin or comments on my dosing and schedule.
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I've been on Rapamycin and Metformin since January of 2017. Maybe a general feeling of wellness but not profound. A definite decrease in my weight setpoint. About 8 pounds lower or about 4-5% less. I was normal weight before and now I'm even lower. (21.5 BMI) Better blood numbers especially triglycerides. I dose at 4 mg a week and run for three weeks and take one week off. My prescription from Dr Green is for 3 mg a week so I bumped it up to 4 mg and take a week off. When I see him again next year I will ask him to bump it up to 6mg a week. 58 years old and overall excellent health. My primary care physician is always asking me to improve something like upper body strength saw me recently and after 20 years finally congratulated me and said I was in perfect health and told me to "keep doing whatever I was doing". He orders an unusually large amount of blood and urine tests every year (for a family doctor). He noted in his charts what I'm on but made no comment pro or con. I've had one minor cold 6 weeks after starting rapa but no colds or flu since then.
I tried my first dose of D&Q on April 28, 200mg/2000mg. It's still early but so far the effects are all positive and not subtle. I am very excited about synolytics and I believe they are more important than anything else I've taken.
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Larry My wife saw my good results with rapamycin and metformin so she saw Dr Green with me. (I had been self experimenting before that) She is on 3 mg a week since last April with no metformin. I'm not sure why Dr Green did not put her on metformin but her blood work was excellent when he saw her. She is suffering from a bad case of cervicogenic headaches due to occupational damage to her neck.
The reduction in pain was dramatic. She was able to reduce her use of NSID's from 8-10 a day to maybe 5-10 a week. She is not cured but much better, maybe about 75% better. She also had a similar reduction in her weight setpoint. She just did a dose of D&Q last week and still waiting for results and I'm hopeful we can get her pain under control.
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Larry that's great info, thanks. Even if you didn't feel anything profound, it sounds like the weight set point and general health effects may have been profound. As for senolytics, a word of caution from Michael Fossel here, which makes some sense to me: http://www.lidsen.com/journals/geriatrics/geriatrics-03-01-034. He argues essentially that senolytics will generally give short-term boosts but at the expense of long-term health b/c you're taking out cells permanently that might be rehabilitated. This is currently very much a minority view but it makes some sense to me if effective telomerase therapy is on the way.
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Tam Thanks for the info. Definitely a minority view. How do they explain the D&Q results (significant age extension given at old age) with mice? He has a company that is trying telomerase to cure Alzheimer's. De Grey and SENS do not agree and are not optimistic about this therapy. SASP make up such a small percent of your total cells that it makes no sense to worry about their loss. Trying to save them also risks cancer IMHO. Anyway, there are now at least 12 human studies underway and one completed, so we will get more answers in the future. I do not recommend D&Q unless you are in your 50's and your risk tolerance is high.
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Larry I agree with this view of telomerase. https://www.fightaging.org/archives/2015/04/telomere-erosion-is-complex-but-looks-more-like-a-measure-of-damage-than-a-source-of-damage/
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Larry A gentleman, Robert H Olander, posted on Josh Mittledorf's site that he has been taking 100mg Dasatinib/1000 mg Quercitin monthly since the winter of 2015. He seems very healthy and still plays tennis 3 times a week at age 83. He has details of his blood, telomere and Horvath test results in the comments. He has taken everything since the '80s related to anti-ageing and the only things he noted an immediate change for the better was Rapamycin and D&Q. Four years and no problems is a good sign. https://joshmitteldorf.scienceblog.com/2018/08/01/the-most-effective-personal-anti-aging-program/
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Tam From the article you posted with a neat graph:
"Repetitive injury (e.g., repetitive trauma to a knee joint in the case of a basketball player, hypertension with accelerated rheological trauma in the aorta, or traumatic brain injury in the case of the CNS) can be represented as “Repetitive Injury” (in yellow)"
"Senolytic intervention should cause an initial improvement in clinical status followed by an accelerated clinical failure with the steepening curve, represented here as “Delete Senescent Cells” (in red). This is precisely what we see in the published senolytic data [27]. Finally, telomerase therapy should cause improvement at both the cell [8] and the tissue levels (as it does at organ and biomarker level [18,19]) represented here as “Reset Senescent Cells” (in green)".
They are mistaking acute senescence with chronic senescence. Acute is good for wound and tissue healing at the site of an injury. Chronic senescence is always bad and increases with age. This is what synolytics clear out. You would not want to take synolytics just before surgery for instance.
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Larry Robert Olander is my Dad! He is 84 years old and he has more energy than I do at age 58! He’s a brilliant guy with an IQ in the 140s and no indication of having experienced a decline in cognition. (Except he has trouble multitasking nowadays). He plays tennis with his 84 year old wife daily, and does some strength training, though I couldn’t say how much or what type. Yay, Dad!
He takes Rapamycin and DandQ but recently has been experiencing some neuropathy in his lower legs, which he attributes to the 100 mg of Dasatinib. He has temporarily discontinued Dasatinib pending medical testing.
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Karl Olander Thanks for the update and wish I your dad well. 100mg a month seems very high. I would only do a few times a year at most but it's all a guess now.
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Tam the question to ask might be does D&Q tend to clear chronic (persistent) or acute (short term) senescent cells. If it affects those persistently senescent cells then periodic dosing of some kind (monthly/quarterly) would be of great benefit.
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Larry What were the non-subtle positive effects if you don't mind listing?
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Charles Richardson Best cycle power levels I've seen in 7 years I have been tracking. Improved energy and mood. I can last 5-10 times longer on a yes4all balance board. No lab work yet.
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Larry Thanks, Larry. I'm just about to try it.
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Charles Richardson test your balance before and after.
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Larry That's interesting. Unfortunately I was just at a company I'm working with that has a specific and objective testing procedure for that...
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Larry Shortening telomeres do affect gene expression as Steve Horvath pointed out as counterpoint in the article’s comments section. Hence telomeres are not just an odometer of our cellular aging.
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Update on my ten week self-experiment with rapamycin. I made it to week seven and then discontinued. I hadn't noticed much of anything in terms of positive effects (measured by workout data like run times, weight training, as well as sleep monitoring, weight, etc), and I did find a pretty serious downside which seems to have been caused by the rapamycin: a loss of libido. It was starting to get in the way of my relationship with my gf so I've discontinued for now. We have been having sexual issues lately already so this just exacerbated those issues and I couldn't deal with it at this time. May try another trial down the road if more data comes in showing positive effects from low dose rapa.
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Tam Hi ....I had the libido drop off awhile back...and due to an issue my son has I went to check and T was 230.....clinically low....got a script for T (Androgel at the time but using other generic T gels) ......very helpful.....always check this....and I wonder if you libido is peaked with any visual stimulus other than your GF.....men (not to say you!) are notorious for discarding what's good for a shot a what's maybe better.....suffice it to say that it may be hard wired into us for evolutionary (propagation) purposes and may be creating a subtle urge to 'create the harem' regardless of our adopted value systems and resistance to polygamy. This is my personal supposition and one I think men should be aware of as they reflect on their relationships. May be time to gift her some particularly inappropriate lingerie. Been there doing that. All the best!!!
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Hi all, I wanted to chime in on this Dr. Alan Green thread. My wife (51yo) and me (54yo) spent 5 hours with Dr. Green yesterday. My wife is a very healthy 51yo. Low BMI, fantastic blood markers, good genes (negative E4). She does have thyroid issues (Hashimoto’s) and has some osteoarthritis. Dr. Green placed her on 1-3 mg Rapa weekly primarily to see if it will help the early arthritis in her hips and feet. I’m a 54yo with a poor family history, one allele of E4, diagnosed low-count Monoclonal B-Cell Lymphocytosis. I have a tendency to put on weight. We both follow a primarily plant-based diet. I do have some history of hypertension as well and currently my BP runs 135/85.
Dr. Green put me on 6mg Rapa weekly, ARBII BP 16mg daily, Cialis 5mg daily, Doxy daily, and wants me to try one dose of D&Q for senolytics.
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Sam Biller did Dr Green explain what each you meds are for?
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Karl Yes. He went over them in detail. There is a paper online that discusses each of them.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5482593/
They all have, at a minimum, animal studies that show an anti-aging effect. I believe Dr. Green himself is on most of them.
I’ve had to stop taking the Doxy daily. It was causing incredible reflux so I discontinued. The Doxy was primarily a prophylactic anti-biotic because I have a slight tendency for bacterial infections. I do have a script for a Z-Pak from Dr. Green which he insists on using whenever a patient has a fever over a certain threshold.
You’ll see from the paper linked above that there is significant evidence that, in addition to Rapa, Tadalafil and ARBs have an anti-aging effect with very few side effects.
Prior to the ARB, my BP was running 135/85 and now it’s running 120/75.
Hope this helps.
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Sam Biller thanks. I coincidentally found that article last night. Great info. Seems some drugs like Rapamycin clearly work, but others have minimal evidence, or only alleviate symptoms of old age, or alleviate side effects of other drugs.
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Sam Biller I second Karl's thanks Sam. Great article! I've been wondering how all the lowering mTOR meds/lifestyle mods compare in their effects on mTOR so the diagram with the different font sizes reflecting the amount of inhibition was just what I've been wondering. I'll be trying the Lisinopril I got over a year ago again since it appears to have a reasonable amount of mTOR inhibition which I did not recall (75 yr. old on Met for over a year, ran out of rapamycin a year ago and have not repurchased since we have cal. rest./protein rest. etc. and I'm trying some herbal rapalogs also).
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I have been taking 5mg Rapamycin for the past two years. Recently had a lesion on my forehead that turned out to be Squamous Cell Carcinoma. My Derm who is a young guy and a Mohs surgeon, said he though that the squamous cell may be related to Rapamycin. He said that when he was a resident they saw a number of folks taking Rapamycin for transplant and they had a large number of Squamous Cell Carcinomas. He did say they were taking Rapamycin daily and they had a "lot of Leisons". He said to be careful as he surmised that Rapamycin may slow the immune system down ever so slightly and any propensity to developing skin cancer may be aggravated. Has anyone run into any potential immune problems?
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djmichel are you taking 5 mg daily or weekly? Dr. Green and everyone else I know who recommends rapa for longevity is very clear that it's not to be taken daily but only intermittently for the specific reasons you mention. It is used on label as an immune suppressor but used intermittently it apparently can mimic dietary restriction, with all of the longevity benefits that carries, and avoid the immune suppression. In fact, work by ResTORbio and others has shown that rapalogs are immune boosters, though of course their recent phase 2 trial did not work out for their commercially-oriented rapalog.
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