This data is too extensive; it can only be fully explained through a dedicated article, supported by references to research papers. I will take the time to do this. I may be overly obsessive about perfection. For example, in resistance training, I look to research papers to determine the optimal rest time between sets, the optimal training volume for each muscle group, the optimal total weekly training volume for each body part, and which exercise yields the best electromyographic (EMG) activation signals. I strive for perfection in every aspect, and the key is to rely on experimental data from peer-reviewed papers. Iād like to recommend Jeremy Ethier hereāhe has helped me fill in a lot of information.
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What hard endpoint data in humans do you have with rapamycin? Indirect markers on the other hand are often based on human data.
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https://www.nature.com/articles/s41586-025-09873-4
Scientists around the world are trying to bypass the negative effects of growth hormone on lifespan in order to regenerate the thymus. I think I have already argued many times that growth hormone regenerating the thymus does not mean you can obtain the corresponding benefits ā this has been a definitive conclusion in the decades of growth hormone application in humans. Exploring pathways such as FLT3L, Notch, and IL-7 for thymus regeneration is the likely correct intervention. The GH/IGF-1 pathway is so notorious that everyone knows it.
Based on a vote taken on the last day of the workshop, the strategies believed to be most promising by the panel of invited experts and authors of this manuscript are as follows: 1. Pharmacological inhibition of the GH/IGF-1 axis
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A number of things:
You make good points but beat the dead horse. Just repeating the same argument or breaking it down into little constituent bits or trying to make it more ālogicalā doesnāt mean people will suddenly agree with you. You wonāt convert everybody. So make your case and let the chips fall where they may.
Now I think you make some good points, and the most astute one here is the observation that shorter people tend to live longest. NOT just Laron Dwarves who have a complete lack of HG from conception but run of the mill normal people within normal height variations. This tells me that Fahyās refutation of the LD longevity paradox isnāt very robust. He spoke of adaptive changes happening from in utero and that we canāt write our own genetic lottery. But even lifelong LOW-normal levels seem to be protective which by implication makes high levels likely dangerous.
BUT thereās something to be said for having a limited time intervention of a year or so, just to bring thymus back to a younger baseline and hopefully combined with resistance training and all the gym bro stuff (protein, periodization, possibly HRT etc.) should bring the bone and muscle mass up significantly as a pleasant side effect. THEN once those results are achieved, one can taper down to nothing to be conservative and reap the benefits. Muscle mass is easier defended than gained especially for the elderly. Same for bone. Perhaps the organism on lifelong low hgh is primed for longer survival but not if you have a bad fall in your 70s or 80s and are sarcopenic.
I think this is a possible way to have oneās cake and eat it too but of course everything is speculation. And no Iām not taking it yet ā came very close to jumping on the bandwagon but I have reservations and at 39 many cleaner levers to pull first.
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I have also realized that Iāve been stuck in place. Regarding the brief use of growth hormone you mentioned, Iāve already considered it. However, the short-term spike in GH/IGF-1 levels may have permanent effects on lifespan. I just hope people will read more papers before making a decision.
https://faseb.onlinelibrary.wiley.com/doi/10.1096/fj.202200143R
we show that transient early-life GH treatment leads to permanent alteration of pertinent changes in adipocytes, fat-associated macrophages, liver, muscle
This brief GH exposure reverses the various benefits originally seen in long-lived mice. The key issue is that growth hormone has been used for decades, yet its effects on cancer risk, cancer mortality, and all-cause mortality show no net benefitāand may even be negative. Moreover, lifespan has been shortened in many mouse strains. A very simple question is: what is your goal in pursuing thymus regeneration? Of course, I donāt want to repeat myself. You guys make your own decisions. Iām just trying to provide a few references.
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Yes again you make a good point but weāre not talking about pulsatile EARLY life exogenous hgh supplementation but pulsatile LATE life. Very different beasts, possibly. At an early age everything is more likely to affect the trajectory of an organismās growth. Think of those mysterious compensatory mechanisms taking shape. Later in life there can be very different effects. Rapamycin too exerts very different effects based on age at start of supplementation.
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Well at least HGH makes you look better 
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Dunno Iām pretty hot already 
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he also abandons things when they donāt work: he has taken human growth hormone, for example, but stopped because the potential side-effects were too egregious.
How should I put itā¦ Many arguments have been repeated many times. I think adding more information is of no benefit. I just want to briefly add one point: currently, there are many studies on safer ways to regenerate the thymus that are ongoing, but the president has suspended a lot of research funding.
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I donāt take Bryan Johnson as a model of decision making on anything other than how to build a company from scratch with Mormon work ethic and how to sell it for $800mm. Super impressive but the domain competencies there donāt necessarily translate.
You yourself not a few posts ago derided him for axing rapamycin due to useless biometric data as opposed to keeping an eye on the ball for the end point data. So he was wrong about dropping Rapa but right about dropping hgh even though he presumably employed the same thought patterns to make both decisions?
Again Iām not sold on hgh but noting that the argument from authority doesnāt hold here.
We also havenāt discussed the amount being dosed yet. Fahy adjusted the amount of hgh with deploying the minimum viable amount to achieve his effects on the thymus. They werenāt supraphysiological amounts if memory serves but rather closer to the upper range of normal youth levels of igf-1. Maybe 200-300 ng/ml. Do we have sub cohort data on the negative effects based on what the serum levels of igf-1 were or is it a binary comparison between those who got jabbed and those who didnāt? I ask because this is an easy drug to abuse and those who self select towards taking it tend to be higher risk takers.
Anyway judging by your profile youāre very young, in your 20s. So this is not your fight at all. Iām 39 and still consider myself too young to make the risk reward calculus at all attractive. For someone in their late 60s, or 70s, or 80s, they might not afford more time until these safer thymus rejuvenation methods emerge. But still Iād tread very carefully as older folks are more prone to cancer.
Look Iām just playing devilās advocate here and my 2 cents are that this is a highly speculative area with messy information. The right call to make depends on the person, their sex and age, what other options they have, and their risk tolerance. I would never encourage anyone at any age to dose it very high.
But a better question than you to the hgh-groupies of whatās their purpose in rejuvenating the thymus might be, whatās your purpose in aggressively trying to dissuade people from taking it? If the data were completely black and white I think thereād be consensus but it just isnāt. So itās a Rorschach test.
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One more thing: another conclusion that can be drawn from Gregory M. Fahyās paper data is that a total of two subjects had abnormally low baseline thymus fat content (i.e., a high thymus fat-free fraction, TFFF). These two subjects showed no significant improvement in their thymus fat-free fraction after the intervention. So, if you decide to inject growth hormone to regenerate the thymus, it would be best to get tested first. Thatās all I have to say. I no longer wish to provide any further analysis. Thatās it.
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Where does this quote come from ā itās not in either article you cite in the post. In fact the cited article fails to support your point, and somewhat goes against it, as it provides evidence for the idea that GH signalling exerts most of its lifespan effect from exposure in late development, rather than maturity. This idea is well enough established by now that we can perhaps take it as proven, in mice at least. IIRC there is some mouse evidence that GH in adulthood has a nonzero, though much smaller effect. You donāt cite this, and skimming your sources down-thread all of them speak to the effects of early exposure.
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