#42

One has to consider that this may be as much a business decision as it is an individual health decision.

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#43

I take everything you mentioned and think they’re safe.

I still think Rapamycin is safe (my strongest concern would be potentially higher A1C) but I am interested to see if Bryan notices any changes the longer he’s off from it. Since he tests so many things, it would present a stronger anecdote than most I would think.

Lustgarden is proving that only diet and exercise alone are quite effective. I did notice in his recent video that his Free T3 and DHEA-S levels were low though. He’s trying to raise them naturally but I think it’s nearly impossible without directly taking these hormones.

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#44

Sure - I would state the same about biomarkers themselves.

It seems clear LDL and a1c are causative in disease when too high - so there definitely is value in them.

When we look at how rapamycin extends lifespan in male mice despite causing diabetes and the greater success of combo treatments with rapa and blood sugar lowering meds, and it suggests two things:

First that rapamycin is succeeding in extending longevity in spite of this negative side effect on blood sugar.

Second that the negative side effect can be controlled by additional treatment that produces an even greater benefit.

So its lack of biomarker improvement in humans does not mean it doesn’t work in humans - it may mean we don’t currently measure the benefit it is having. That it is working in spite of the negative effect on biomarkers. And if we can control those biomarker side effects - a1c and ldl - with additional interventions then we could get an even greater effect.

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#45

Exactly. He can’t sell you rapamycin as part of his ‘Blueprint.’

But maybe he knows what he’s doing. After all, he looks like 50 going on 15.

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#46

And beyond LDL and a1c, it is pretty speculative which biomarkers are causative.

Muscles are correlated with longevity, and steroids increase muscles, but do steroids increase longevity? Probably we think the answer is no - but if “muscles” was a random biomarker and “steroids” was a random drug - it would be easy to think “yes, probably”.

The danger of mechanistic reasoning is our reasoning is too ignorant at the current time for such a complex system. Whereas lifespan data gives us the result we really care about.

Of course the trouble is - it is impossible to do lifespan RCT in humans so we are forced to use biomarkers, short term mortality or epidemiology for human data.

So we must use biomarkers too, and some like ldl and a1c seem very strong signal, but when lifespan data contradicts it - I’d side with the lifespan data.

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#47

This makes me wonder if there is some sort of connection between HGH and Rapamycin.

HGH is another one that can worsen insulin sensitivity despite having many other benefits when used to fix a deficiency of GH and IGF1. That’s why Metformin was given alongside it in the TRIIM studies.

Both HGH and Rapamycin can improve lymphocytes, and T cells, among other things.

Also, HGH reversed aging in the TRIIM and TRIIM-X trials (I know some have argued against the Horvath aging clocks but I think it’s promising data). Rapamycin increases lifespan among many animals.

(I’m referring to HGH only in physiological doses and not “athlete” doses).

I could be talking out of my ass but I do see similarities.

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#48

An example of how little we know about biomarkers and mechanism - I’ve also read arguments that HGH and IGF1 are both negative for longevity.

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#49

I think the real issue is that Bryan’s doing so many things—taking different supplements, medications, fasting, and he used to do calorie restriction, right. All of that can actually push cholesterol/glucose levels up. I noticed my own cholesterol would rise whenever I fasted. Funny enough, when I was on rapamycin weekly, my cholesterol actually went down, and my heart rate stayed low, around the 50s. I guess I’m just saying there are a lot of factors in the mix. Its weird how he ruled it out to rapamycin, did his cholesterol, heart rate etc lower as soon as he stopped taking rapamycin? would be interesting to see his blood work after stopping rapamycin.

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#50

I didn’t have many problems (arthritis, memory, whatever that swallowing issue was) when I was his age. When he gets older he may notice the benefits outweigh any side effects. I don’t even have any side effects, but the last few days of my 2 weeks my right arm starts to hurt again. I’ve been thinking of going to just 12 days.

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#51

Be careful judging online wealthy people by their looks. BJ has professional photographers taking pics are the best angles and lightning. Not sure about digital touchups. He also had multiple cosmetic procedures…
Bryan Johnson, an anti-aging millionaire, has undergone a variety of skincare procedures, including:

  • Fat injections: Johnson has received fat injections from a donor to rejuvenate his face. After each injection, he looks “so puffed up” that he could have been “chugging bee venom”.
  • Weekly acid peels: Johnson undergoes weekly acid peels.
  • Laser therapy: Johnson undergoes laser therapy.
  • Microneedling: Johnson undergoes microneedling.
  • Microbotox injections: Johnson receives microbotox injections to shrink pores.
  • Collagen production injections: Johnson receives injections to stimulate collagen production.
  • Sofwave: Johnson has used Sofwave, a skin rejuvenation therapy that uses ultrasound to stimulate collagen and elastin.
  • Tixel: Johnson has used Tixel on his face and neck.
  • Lutronic Ultra laser: Johnson has used the Lutronic Ultra laser on his scalp.

So his looks may have not much to do with his actual diet, exercise, supplement…

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#52

I’m on the same page as far as dose - I went from 4 mg every 3 weeks to 4 mg every 4 weeks based on my dose limiting toxicity which is usually aphthous ulcers. This was fine but last cycle I upped to 5 mg and got three nasty boils at around day 10 post dose, one of which was scrotal. Ugh! So - next monthly cycle I am planning to back down to 4 mg. or even 3 mg since I have a bit of PTScrotalD. I think rapamycin is a hormetic drug. From its pharmacodynamics, it is a particularly potent cellular poison and constant exposure is probably not a good idea. On the other hand, a little poison now and then can be quite useful, for example in promoting autophagy as you point out. Fasting is hormetic as well, it also promotes autophagy, some is healthy, a lot will weaken and possibly kill you.

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#53

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#54

I do have some patients who seem to do worse on Rapa. It’s not the norm, but everyone is different. Regardless, it is very difficult to pin down causation when doing 100 things. Additionally, one of the things he is taking (or 10 for that matter) might be interacting in a negative way with Rapamycin and removing Rapa might not be the best approach, getting rid of all the other stuff might be.

This is the problem with taking too much stuff.

If I were his physician, I’d be looking more toward stopping everything, then reintroduce rapa by itself and see what impacts occur.

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#55

Agreed. I would only underline that it is important to use the best possible biomarkers for each aspect for the system.

For example fasting insulin and apoB would be slightly superior markers than A1C and LDL-C.

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#56

Hello Dex, I have not noticed any of those effects either but have come to realize that we are all lab experiments seeking the fountain of youth. Until long term studies are conducted I am hopeful but skeptical. Who knows we may be doing more harm than good or vice versa. I have only been on Rapa for 9 months but feel and look a bit older sad to say. I am going to start Rapa vacations and see how I feel when I’m off.

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#57

Rapamycin is used to promote autophagy. We older folks over 70 with inflamed zombi cells in the body benefit from it, heart function in particular. IMO its not essential for people under 60. Matt K, Brian are considered young.

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#58

I thought Michael was going to be trying rapamycin… so hold that thought…

The latest post from Bryan Johnson doesn’t tell us much that is new… some people get some level of lipid and glucose disregulation at certain dosing levels, thats been known for many years. The frequency and degree of this will vary by person and dose. Similarly some people get rashes and low levels of immune system reactions, but from what we’ve seen here this is a low percentage.

All the other references are just old research papers that may or may not apply to lower dose, intermittent / pulsed dosing as used in longevity applications (and we have no people reporting these issues).

And, as others have pointed out, when a person is taking 100 other things at the same time its really hard to know the direct cause of any given side effect; whether its a single compound or a negative interaction between multiple compounds being taken.

There is a real limit on what conclusions you can draw from N=1 personal clinical trials, and even more limits when you are playing with 100 different variables at the same time.

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#59

Maybe it would be better to cycle Rapamycin? One 60 -90 day a year cycle on it? Or something like that? Thoughts? I thought I remember reading somewhere that you can get many of the benefits by doing a cycle of it.

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#60

Michael has already done the rapamycin experiment, but he quit early because it affected his HR and HRV.

I think it is less likely it would be from interactions because these are common side effects as you say, but it appears not everyone gets them. I wonder if using another mTOR inhibitor instead would help, and if this is from mTORC2 inhibition. Everolimus is different from rapamycin, for example, after all.

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#61

Good question. I’ve got a bunch of Everolimus and I’ll be testing a dosing schedule in the same manner as I’m going to be testing rapamycin, with full blood work and blood level testing every day after testing to see if there is a different effect. But of course, we need more clinical studies.

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