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

#6

Thanks for the advice

I haven’t found doctors in Taiwan prescribing rapamycin yet
And I am planing to take regular blood testing once a year, after hearing your advice, thank you

Yes I have been under constant stress for years, that probably the biggest factor for my grey hair
In the middle of this year, I began to take Sulforaphane 60mg/day, hoping that can lower my inflammaging state

Lastly, sorry for the confusion, I am actually a boy
www.rapamycin.news automatically updated my Gmail profile here by default
I change profile now, hoping that will not confuse you, and still appreciate the information about the rapamycin side effects

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#7

When I read the literature above, it seems like there is an arc that begins at birth and reaches its apogee at some point in late 20s or early 30s when the GROWTH phase of development begins to slow down, creating a down slope all the way to death. Mtor is absolutely crucial in the growth phase and problematic in the decline phase. SO the question is: where is the apex of the curve when starting rapamycin would be beneficial? I don’t think we know that in humans yet, so it could be dangerous to start too soon. As you cite the pregnancy paper above, I think there are very strong lingering concerns about inhibiting mtor in people who are of an age likely to produce offspring. Secondarily, I doubt that a healthy 30 year old is beginning to suffer from inflammation of the bad kind that impeding mtor can help. They are still building muscle and mtor is needed for that. Aiming to start after chilld rearing at age 40-45 makes more sense.

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#8

First of all - I think your view is the dominant view of many of those in the medical profession who are at all familiar with rapamycin (if they are at all supportive of people taking rapamycin), and given the nascent state of the rapamycin clinical trials for aging that may be entirely appropriate.

Also - Its absolutely true that Mtor is critical during growth - so you don’t want to experiment with rapamycin until you stop growing. I’m not a biologist - so I will deign to their expertise if they want to weigh in on this, but all that I’ve read suggests that most if not all human development is complete by age 25 to 27. For example this article talks about 25 for the completion of brain development.

I have a cardiologist friend who says the only thing that keeps growing after that are your nose and your ears - and thats why they seem so large on old people. Perhaps the lack of infinite growth of the nose and ears would be another benefit of taking rapamycin I haven’t mentioned :smile:

I agree there are lingering concerns about the risks of inhibiting mTOR in people of reproduction age and that rapamycin use / mTOR inhibition is definitely not recommended (and the risk, of course, is that someone is taking Rapamycin and doesn’t realize they are pregnant) - so definitely extra caution is required during those age periods.

But - I would argue that given that perhaps something like 25% of organ transplants happen to patients under the age of 40 (see graph below), and virtually all of these patients probably take sirolimus (I believe taking it with cyclosporine is the typical medication protocol used in transplant patients), and I suspect that most of these people also go on to have children (or at least a significant portion). So - I would argue that the medical profession has been dealing with the risk of mTOR inhibition and potential pregnancy for the past 20+ years with rapamycin (as long as rapamycin has been used in this application) and there is not that much difference with it going forward in an anti-aging application with people of this age group. But yes, the anti-aging doctors would need to learn about this and implement these educational programs in their clinics if they treat this age group.

Transplants
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Also - you are correct I think that the typical healthy 30 year old is not going to see much benefit immediately from taking rapamycin in terms of inflammation reduction, etc. and still needs mTOR to grow.

But - we all need mTOR for our muscles to grow, we just don’t need mTOR on all the time for our muscles to grow, and rapamycin for anti-aging protocols are all about periodic dosing, to allow mTOR to return to higher levels periodically to help in muscle growth, etc. when its needed. So - a 30 year old would get that on the periodic dosing schedule just as a 60 year old would too.

Maybe there are a number of factors that will ultimately evolve to drive the medical profession’s thinking on this, and consumer’s thinking.

  1. Current concerns with fertility. This is a common concern of professional women in their late 20s and early 30s who place a high priority on their careers. One strategy they pursue right now is freezing their eggs, but that is an expensive, painful and risky medical process too. While still to be proven, rapamycin may simplify this process. I suspect most women of this age would prefer to take rapamycin at a cost $50 a month or so, than the $6,000 to $20,000 for egg freezing - and all that that entails.

  2. Concern about, and Risk of, Obesity (and how well the research on rapamycin in preventing obesity is progressing). The sooner you can stop the problem of obesity, the better. This is definitely one area where a large percentage of people are still growing during their 30s and 40s - but would probably prefer to not be growing.

  3. Risk / Reward Perception - the science around rapamycin is changing every year, and people all have different risk/reward perceptions and profiles. So I think you’ll see the adoption rate of rapamycin vary as research progresses and the risk / reward profile of taking rapamycin becomes better understood by people.

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#9

You are on the right path here, I think. There are a number of biomarkers that show when a human has embarked on the aging down slope and as testing technology becomes more sophisticated, we’ll know with more accuracy when that occurs.
For example: https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8002905/pdf/CTM2-11-e372.pdf shows that older adults produce less gluthathione than younger adults. When does that start to happen?
This study shows that a protein called CD38 begins to degrade NAD+ as people age, which may be responsible for many age-related illnesses. https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC5885288/pdf/nihms947957.pdf When does that process start?
For females, there is a clear demarcation with menopause. For males it is less clear: when does the level of testosterone begin to decline as DHT increases, causing male pattern baldness and prostate issues? the cause is an increase in 5-alpha reductase that may be the result of a decline in production of progesterone, a natural 5-alpha reductase inhibitor. When does that decline begin?
Another key biomarker is when cells start becoming senescent. The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs There are now senolytic drugs that can help remove them, but a better approach would be to start rapamycin therapy as the process begins.
As it becomes easier to plot these turning points, I think the answer to your question will become clearer.

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#10

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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#11

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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#12

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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#13

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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#14

@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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#15

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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Rapamycin & Testosterone
#16

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

#17

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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#18

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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#19

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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#20

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?

#21

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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#22

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

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Rapamycin & Testosterone
#23

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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#24

@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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#25

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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