#42

Steve Horvath decided to try it on his own (not part of the study) but without HGH, and he hasn’t gotten the same results as the people in the study who are using HGH.

I’m interested to know more about what Dr. Horvath tried and found. Do you happen to have details?

I feel like I’m misunderstanding something, because I would expect that he doesn’t get the same results if he doesn’t take the treatment that’s hypothesized in the study to result in thymus regeneration (i.e. GH).

From the TRIIM paper (emphasis mine):

The purpose of the TRIIM trial was to investigate the possibility of using recombinant human growth hormone (rhGH) to prevent or reverse signs of immunosenescence in a population of 51‐ to 65‐year‐old putatively healthy men, which represents the age range that just precedes the collapse of the TCR repertoire. rhGH was used based on prior evidence that growth hormone (GH) has thymotrophic and immune reconstituting effects in animals (Kelley et al., 1986) and human HIV patients (Napolitano et al., 2008; Plana et al., 2011). Because GH‐induced hyperinsulinemia (Marcus et al., 1990) is undesirable and might affect thymic regeneration and immunological reconstitution, we combined rhGH with both dehydroepiandrosterone (DHEA) and metformin in an attempt to limit the “diabetogenic” effect of GH (Fahy, 2003, 2010; Weiss, Villareal, Fontana, Han, & Holloszy, 2011). DHEA has many effects, in both men and women, that oppose deleterious effects of normal aging (Cappola et al., 2009; Forti et al., 2012; Shufelt et al., 2010; Weiss et al., 2011). Metformin is a powerful calorie restriction mimetic in aging mice (Dhahbi, Mote, Fahy, & Spindler, 2005) and has been proposed as a candidate for slowing aging in humans (Barzilai, Crandall, Kritchevsky, & Espeland, 2016). Neither DHEA (Riley, Fitzmaurice, & Regelson, 1990) nor metformin are known to have any thymotrophic effects of their own.

#43

He uses growth hormone. I think he also uses some dhea and metformin because gh causes blood sugar to go up. As far as I know, that’s basically it.
If you can get gh it doesn’t seem so hard to try it yourself. The idea is that the thymus is regrown which is supposed to boost the immune system to that of a younger person.

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#44

Here is a video on YouTube where Fahy is giving a talk about TRIIM X and mentions at 3:15 that Horvath was curious so he decided to combine Metformin and DHEA and then do the age test the study subjects did and didn’t get the same results.

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#45

We’ve done the items in TRIIM-X ourselves coming up on 12 months now.

The protocol is the same, but is self funded to be part of his trial. We have not been part of his trial.

It is modestly expensive - but if getting HGH in the U.S. it is absurd - getting reliable off shore is still not cheap.

The issue now that I’m on rapamycin is cycling it. As HGH stimulates MTORC2 (I believe) we have chosen to hold our HGH for the 3 days post Rapamycin, and be on a q8day cycle for Rapa, so 5 days of HGH. We also have DHEA, Metformin, Zinc, D3, K2, etc.

The thymus degenerating and thus one’s T cell immunity degenerating is likely why old people get severe outcomes with viral illnesses (e.g. covid, flu, rsv and others) and also why cancers go up with age as your T cells fail to recognize malignancies and clear them out. I appreciate that it is more complicated and multifactorial than this - but it is part of the picture.

This is probably our biggest motivation for doing this. The risk is HGH will stimulate IGF-1 (which we measured and my wife was Z score -0.1 and I was +0.1, so not really a big factor at 1.5 and 2. units/day respectively). We do worry about premature aging with use of HGH, but my feeling is that this is likely a dose issue, and certainly for people doing big doses, it will rapidly age them.

We are considering where we end with HGH - probably 15-18 months of use, I think.

What I’ve heard from Fahy, is that the TRIIM-X is not looking as favorable – BUT this is the huge problem of letting people self enroll - the group enrolling are already health nuts and already have done so much to optimize their health and aging, so the ability to improve on this is massively blunted compared to his initial cohort. The very method by which people TRIIM-X is bound to be its undoing and will certainly show little effect because of super well people who have already biohacked everything … how much is HGH going to add to their aging? Probably only a tiny bit.

I anyone else doing Rapa/HGH and are they cycling it like I am to boost recovery from MTOR inhibition once serum Rapa levels are low?

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#46

Very interesting and thanks for sharing. I’m also taking the HGH as well (2iu before bed every night. I’m 203lbs for reference). I also take Rapamycin and everything else as well plus I’m only 38 so I probably won’t get the same benefits either. I like the cosmetic effects enough to keep it in though.

Are you doing the same dose as they’re doing in the study? 0.045iu per kg of body weight 3-4 days per week?

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#47

I didn’t see a medical reason to just do 3-4 days per week. So I’m 165 lbs, and do 2 units 7 days per week which roughly works out to 14 units per week which is similar to 4 days of dosing on Fahy’s protocol.
I’d see more risk of hyperglycemia and igf1 stimulation taking 4 units at one time which would be the case on Fahy’s protocol.

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#48

So we are on the exact same dose then.

There actually is reason to inject 3x per week apparently. Seems to be better for insulin sensitivity and slightly better for lean mass but worse for lipolysis. I don’t know how big of a deal it is either way though. It’s easier to do something every day IMO

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#49

Very interesting - thanks for this. Excellent to learn something new. Suspect that might be why the protocol is as it is.

Regards,
Grant

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#50

FWIW

“Recombinant growth hormone (GH) therapy in GH-deficient adults: a long-term controlled study on daily versus thrice weekly injections”

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#51

I was going to also post this one but felt two studies were enough :joy:

#52

I’d be interested in hearing people’s thoughts on using a GH secretagogue in lieu of rhGH.

For example, ibutamoren is much easier to administer (oral) and obtain.

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#53

I really think HGH gets a bad rap. I wish it would get studied more because there are definitely a lot of benefits. As long as you tackle the issue of increased insulin resistance from it (Acarbose, Empagliflozin, etc), I don’t see a downside if used at physiological dosages

#54

Not as good IMO. I hear benefits don’t last forever and you have to cycle (someone correct me if I’m wrong). I’d rather just use the real thing. And honestly, unless you jump through a million hoops to get an extremely expensive prescription for HGH, the precursors are really not much cheaper.

#55

medaura, You now have my interest. Where are those before and after pictures? If a real person like you has good results I’ll consider pursuing some type of treatment myself. However, I remain very skeptical that treatments of any type will be of any benefit to me.

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#56

DrFraser, The thing that has concerned me since reading about TRIIM is that once you stop the therapy the thymus will begin involution again, I assume. If this is the case how long will the results of the TRIIM or TRIIM-X trials last? Do you have any thoughts on this?

#57

Another issue…

While the first TRIIM study seems to have been somewhat successful, The Buck Institute has done a study on aging clocks and Eric Verdin has posited that the results that Greg Fahy announced with the first trial may be a false positive because of how the bioclock used measured things inaccurately. He said he contacted Greg Fahy to see if they could run his results with the new Buck Inst. clock, but didn’t get a response.

Eric covers the issue in this presentation:

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#58

We think new sets of T cells will continue to be active (as far of the effects of regeneration) probably for 8-10 years. We have no idea if doing the regimen 8 years from now will result in a second regeneration of the thymus and T cells.

This is the challenge – does one stop at 12-18 months, or continue on longer term? What are the risks of relatively physiological doses of HGH on longevity beyond this use for a year or so? Could the main benefit be a year of therapy, or could it be required to stay on it to achieve a sustained positive outcome - or could sustained use worsen outcomes?

The TRIIM trial and TRIIM-X are going to solidly fail to answer these questions. It leaves one with fascinating situation in this space of again not having sufficient data to be certain on what the situation is, and what the longer term role of this type of protocol is for longevity.

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#59

I am glad I listened to the video posted by @RapAdmin again.

I think TRIMM should really be open to scrutiny of their DNA results.

I have been thinking about what causes methylation of the DNA to occur. I am thinking there may be a relationship between failure of transcription and methylation. This would be something that would make the process of transcription (and potentially alternative splicings) to be a bit sticky.

Hence the distinction between epigenetic age of the different cells with some clocks, but not the clock that Eric Verdin refers to.

Hence it does appear that TRIMM was basically measuring something not relevant to the aging process.

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#60

My only thing with Greg was the fact that he looks real good/young for his age. Plus, he actually looks younger today than he looked 5-7 years ago. I can’t say that for any of the Dr/people in the antiaging field. So, I don’t know about aging clocks but whatever he is doing I’d love to do. The problem is he is elusive, because I don’t think he only does the TrIMX thing. He did mention he takes a lot of supplements but when pressed he only mentioned Carnosine. I’ve been taking carnosine for last couple weeks and I do like it a lot but can’t say what it will do long term. I intend to keep it in my stack.

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#61

He has obviously started taking care of his skin and hair in order to look younger because why would anyone trust a “longevity expert” who doesn’t look young (for their age)?

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