The Case for Starting Rapamycin Earlier in Life (e.g. late 20s) vs middle age (e.g. 50s)

Here’s another reason younger men probably would not want to take rapamycin:
“Treatment with TOR-I results in a decrease in testosterone level, and an oppos-
ite increase in LH. Moreover, spermatogenesis seems to be disrupted by TOR-I
and FSH levels are increased.”

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Yes - we cover that in the animal study risks section. In organ transplant patients taking rapamycin daily it has been shown to be reversible when they stop taking rapamycin.

Regarding the impact of sirolimus on sperm, there was a recently published a case report on a 36-year-old male kidney-transplant recipient treated by an immunosuppressive regimen that contained sirolimus. He presented with dramatic, reversible sperm impairment. He initially (for 3 months) 2 mg/day of sirolimus associated with 10 mg/day of prednisone, 200 mg/day of cyclosporine, and then for 33 months 7 mg/day of sirolimus and 10 mg/day of prednisone. During this time he could not get his wife pregnant. When he stopped taking sirolimus, he could and did get his wife pregnant.

I haven’t seen any people reporting this issue with pulsed, periodic dosing of rapamycin.

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The reason may be that most of the people taking rapamycin on a pulsed basis, i.e. for anti-aging, have already reached an age where they no longer care about sperm counts. But the decline in testosterone would be unacceptable to many younger men.

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We cover a review of all the papers on this topic on the Risks page. The impact on gonads/spermatogenesis is seen in higher dose, continual dosing of rapamycin as is used in organ transplantation and cancer treatment. In the review (the same review that you posted) focused on organ transplant use of rapamycin it states:

The authors confirmed that total testosterone was lower and FSH and LH higher in the group of patients treated with sirolimus than in those from the control group, and in multivariate analysis, only the use of sirolimus was significantly correlated with decrease of testosterone (age, race, etiology of renal failure, transplant and dialysis durations, antihypertensive and non-mammalian target of rapamycin-I immunosuppressive treatments not significant). However, even though the IIEF score was slightly lower in the sirolimus group, there was no significant difference in sexual score between the two groups (mean IIEF score: 49/75 in the sirolimus group; 52/75 in the control group). Moreover, free testosterone levels did not differ significantly between the two groups.

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@LeeJohn are you seeing any significant issue with rapamycin and testosterone levels at your current dosage of rapamycin (I think you’re taking around 6mg / week - is that correct)? And you’re in your late 20s, correct?

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I realize this is anecdotal and N=1, but i tested 1092 total testosterone 8/15, 482 on 10/28 after 10 weeks 6 mg sirolimus intermittently, and 649 12/3 after a four-week washout. So while reversible, it’s a significant decline, nonetheless. You might add that test to your Life Extension regimen. On the other hand, my calculated bio age was 40 years younger.

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Ah - that is actually really interesting. Its the first time I’ve seen testosterone numbers from people using rapamycin for anti-aging. Thanks for sharing.

Yes - definitely something people might want to consider testing to track over time.

https://www.lifeextension.com/lab-testing/itemlc140103/testosterone-free-with-total-blood-test

Yes I am in late 20s, and plan to take 6mg+grapefruit / bi-week, now I am taking 2mg+grapefruit / week

For the testosterone levels, I only have the basal data before the rapamycin usage, I will have blood test few months later to see if rapamycin increases/decreases my testosterone level

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Regardless of the actual measure of testosterone - how are you feeling? Do you notice any of these symptoms below, and are they at a level where they bother you?

What are the symptoms of low T? Regardless of your age, low T symptoms can include:

  • erectile dysfunction, or problems developing or maintaining an erection
  • other changes in your erections, such as fewer spontaneous erections
  • decreased libido or sexual activity
  • infertility
  • rapid hair loss
  • reduced muscle mass
  • increased body fat
  • enlarged breasts
  • sleep disturbances
  • persistent fatigue
  • brain fog
  • depression

From here:

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I do weight training 3 times a week, my muscle mass didn’t decrease after rapamycin
However, My Body Fat Percentage was from 12% to 8%

I did have decreased libido, but I think that’s because it’s getting cold, I generally have lower libido in winter
Thanks for the T symptoms checklist, I will keep monitoring it to see if rapamycin influences my testosterone level

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That is a pretty amazing biological age reduction. Have you tested it over time? Did rapamycin seem to have any effect or was it other things you are doing or taking?

I’ve been tracking those biomarkers for at least five years and used a different formula for biological age. The gap has definitely grown since starting rapamycin. My thought is that those estimators are heavily influenced by two things: overall inflammation and the health of the cardio system. I have an extremely low CRP score, which I put down to 1. good genes 2. lifelong runner 3. ectomorph with BMI of 20 4. 31 inch waist (believing that belly fat is where the inflammation tends to accumulate) 5. supplements such as beta-glucan to reduce inflammation 6. making sure the gut is healthy with LOTs of fiber feeding the bacteria there 7. frequent saunas (see dr. Rhonda Patrick on saunas) and 8. cold water therapy a la wim Hof, which challenges the immune system.I eat more or less low-carb and my blood chemistry is good (e.g. TG 70 HDL 71) After a piece in the Financial Times many years ago about why London bus drivers had much higher incidence of heart disease than the ticket takers who were on their feet all day, I bought a stand up desk and try not to sit much during the day. Oh, and i have a dog who requires long walks.

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I had 950 total testosterone even after doing 10mg/week regular rapamycin

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Your information is strong confirmation of Peter Attia’s assessment that one should first optimize nutrition and exercise (and sleep and emotional health) and after you get these fundamentals right, look for even greater effectiveness from exogenous molecules (ie. rapamycin, etc.).

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@RapAdmin
Hello
I am a 24 year old male and I have a longevity doctor in the area who I talked to in regards to starting rapamycin. He said via Dr. Blagosklonny and other experts he talked to that I could start now since I am close to 25. I was wondering if you had any thoughts on starting this young? If it would even benefit me right now or if I should wait a little longer( I turn 25 in August). This doctor would obviously do blood work and everything before hand, but just curious on thoughts.

Thanks

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If I were you, and I had any safety concerns, I’d probably go for a less frequent dose (e.g. once a month), or longer rapa breaks. That way I’d imagine there would be higher benefits to risk ratio.

I’d also maybe focus on building muscle – I regret not exercising and building muscle in my 20s because it seems like the easiest in that age.

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Well I would start at 1mg once a week, and then slowly work my way up.
I do a lot of longevity related training such as zone 2 cardio or I do body weight / KB work. I do a lot of gymnastic work and yoga as well. I think the thing I really want to improve on is diet. I eat relatively healthy but I feel that can always improve. Just hard to know what is the right thing to do as there so much conflicting research out there. I fast and time restrict my eating as well but again there is conflicting data on when the best time of day to break that fast is or to consume your meal.

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We’re not medical doctors here - so keep that in mind and we are all just stating our unprofessional opinions.

I think it would depend. If a person is 24 years old, pretty athletic and healthy, eats well and exercises frequently - then I think the person is unlikely to gain much from rapamycin in the next few years, and little to no risk in delaying until 28 or 30 years old.

If on the other hand, I was a not athletic, didn’t eat that healthy (avoiding simple carbs like sugar, etc.), and perhaps slightly overweight or worse, your life is high stress - then I think there could be a case for starting lower dose rapamycin periodically as part of a move towards getting healthier overall (in which case more exercise, better diet, and being a healthy weight would all be important parts of the equation).

But like everything - there is a risk reward calculation to be done by people at any age starting rapamycin. Rapamycin is not a risk-free drug… so you need to learn as much as you can about rapamycin, and work with your doctor and try to figure out what is the best balance for you.

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I am very healthy and athletic. I have done plenty of research( thanks to a lot of your linked research articles). I just wasn’t sure if it would really benefit me much at this point, also I havent had kids yet, so not sure if its worth getting on now, or waiting a couple years.

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In your situation, waiting is probably the best choice. the state of the science is moving forward relatively quickly these days - so the longer you wait, the better information you will have to make your decisions. the “opportunity cost” of waiting for you (because you are still very young) is minimal I think.

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