19 replies to this topic

[lukas_93]

Did anyone hear about the TRIIM Study by Greg Fahy, I just read about it here: 

 

https://www.zeit.de/...ie-gregory-fahy (german)

 

This is the only english article i found 

https://www.tellerre...Bkgc43H8bB.html

 

I can't find anything related to the presentation online though. 

 

According to the article they used: 
- DHEA 
- Metformin 

- HGH 

to modulate thymus activity

 

 

Does anybody know more? 

[sthira]

Thymus regeneration? You’ll correct me if I’m wrong, or someone will, but I don’t think Dr. Fahy’s results panned so well as anticipated. Am I misinformed? Tell me. Because I’m not totally clear what’s going on with their thymus regeneration efforts since to my knowledge they’ve not released data from their very small scale trials.

I’d love to learn more. And others are working to restore the thymus — all of this is good news, imho.

Meanwhile, From Fahy's patent:

https://www.google.c...tents/US6297212

“The regimen for administering human growth hormone and DHEA or their equivalents for the rejuvenation of the thymus is as described above in the preferred embodiment.

“The regimen should be continued preferably for 1-3 months.

“For best results, this regimen can be supplemented with other immune-system strengthening agents, particularly coenzyme Q10 (10-200 mg/day), Vitamin E (200-1000 IU/day) and zinc (30-100 mg/day). Further, chromium picolinate (100-1000 micrograms/day) may be used to supplement DHEA/DHEA-sulfate.

“First, insulin sensitizing (and therefore lowering) agents other than DHEA and its above-described relatives can be employed in place of DHEA. Chromium picolinate and similar formulae involving chromium (such as “GTF” or glucose tolerance factor preparations available in health food stores) and phenformin represent the only known members of this class of agents. As in the case of DHEA, the appropriate dose is to be adjusted based on the insulin-lowering response attained in a particular patient. Chromium picolinate is particularly exciting because of its low toxicity, its ability to extend the life span of animals by 50%

“Consequently, a third choice for thymic regeneration is to use 30-130 mg/day of zinc plus 200-1000 IU/day of Vitamin E plus 10-200 mg/day of coenzyme Q10 for 1-3 months. This approach will be desirable when HGH and DHEA or their equivalents cannot be used for any reason.

“...a surgeon skilled at thymic biopsy retrieval injects into the thymus an appropriate sample of the tissue or organ to be transplanted later, or injects any other donor-specific cells or antigens (for example, bone marrow cells) that are the immunological equivalent of the tissue itself in stimulating deletion or anergy of the cells otherwise responsible for later rejecting the transplanted tissue or organ.”

While we wait, I’m not advising this, but here’s one possible (but probably ineffective) strategy to regrow that thing:

1: Baseline—begin 15 gm/day administration of arginine;

2: Day 7—begin 180 mg/day DHEA;

3: Day 14—begin 15 gm arginine every other day or 7.5 g/day; and

4: Day 21—end of experiment, no arginine administered the previous night.

--DHEA equivalent dose of 50-2000 mg, more preferably 50-1000 mg/day...

I need references, don’t I, and seem to have lost them. Keep digging, folks, the health and regrowth of your thymus is super important.

[Harkijn]

For more background to this also read this older thread:

https://www.longecit...s-rejuvenation/

Edited by Michael, 08 September 2019 - 01:48 AM.
Removing Google tracking materials (no malfeasance on poster's part).

[8bitmore]

Cheers to lukas_93 for getting here early, an update was released on the outcomes from this study yesterday (https://www.nature.c...586-019-02638-w). Would love to see actual basic research paper but have had no luck getting access to it so have no idea about specific dosages..etc. as of yet.

 

Here's excerpts of interest from the article:

 

"In a small trial, drugs seemed to rejuvenate the body’s ‘epigenetic clock’, which tracks a person’s biological age

...

For one year, nine healthy volunteers took a cocktail of three common drugs — growth hormone and two diabetes medications — and on average shed 2.5 years of their biological ages, measured by analysing marks on a person’s genomes. The participants’ immune systems also showed signs of rejuvenation

...

The Thymus Regeneration, Immunorestoration and Insulin Mitigation (TRIIM) trial tested 9 white men between 51 and 65 years of age. It was led by immunologist Gregory Fahy, the chief scientific officer and co-founder of Intervene Immune in Los Angeles, and was approved by the US Food and Drug Administration in May 2015. It began a few months later at Stanford Medical Center in Palo Alto, California.

....

In the TRIIM trial, the scientists took blood samples from participants during the treatment period. Tests showed that blood-cell count was rejuvenated in each of the participants. The researchers also used magnetic resonance imaging (MRI) to determine the composition of the thymus at the start and end of the study. They found that in seven participants, accumulated fat had been replaced with regenerated thymus tissue.
....
Checking the effect of the drugs on the participants’ epigenetic clocks was an afterthought. The clinical study had finished when Fahy approached Horvath to conduct an analysis.
....
Horvath used four different epigenetic clocks to assess each patient’s biological age, and he found significant reversal for each trial participant in all of the tests. “This told me that the biological effect of the treatment was robust,” he says. What’s more, the effect persisted in the six participants who provided a final blood sample six months after stopping the trial, he says.
....
'Because we could follow the changes within each individual, and because the effect was so very strong in each of them, I am optimistic,' says Horvath."

[Harkijn]

I  place the full study for your scrutiny here. You may also want to check Josh Mitteldorf's take on this on his website Aging Matters. 

 

 

Attached Files

•  Fahy2019-GH-EpiClock.pdf   2.51MB   36 downloads

Edited by Harkijn, 07 September 2019 - 03:43 PM.

[GreenPower]

After reading the article in Nature I had thoughts on trying this regimen myself.

 

Then I read the study attached above and also the in-depth analysis at Aging Matters.

 

I think the main problems to solve is that:

1. You need a medical prescription to get hold of Metformin, DHEA, and Omnitrope in Europe.

2. At the "Beginning at the fourth week, all doses were individualized based on each volunteer's particular responses". So the doses need to be personalized.

3. You need to take multiple MRI's and two methylation testing procedures in order to verify the results.

 

It will be kind of hard to do this regimen without access to a willing doctor/lab and some serious money, but if anyone out there accepts enrollments from Europeans for a new study, I'm a willing test subject.

 

 

[Mind]

I talked to Dr. Fahy at RAADfest after his presentation. There seems to be little doubt in their result of reversing thymus involution and partial rejuvenation of the immune system. I just cannot get over how simple the protocol is. DHEA, rhGH, and metformin have been available for a long time. One would think that someone would have discovered at some point in the last few decades that taking these therapeutics in some combination resulted in some sort-of improving health markers.

 

Dr Fahy said that he did not have an answer for why this result has not been achieved or noticed previously, considering that thousands of people have taken growth hormone. He said the that the blunting of the insulin signaling pathway by DHEA and metformin  (while on growth hormone) must be the key to getting this positive result.

[Harkijn]

For quite some time I have been reading up on the scientific discussion of Horvath's clock. Though there is tremendous respect for his achievement  I have come across many doubts and reservations. His clock is by no means a golden standard yet. So I wonder if  Fahy validates Horvath or viceversa. This is how science often works but I am not taking HGH as yet!

[sthira]

I talked to Dr. Fahy at RAADfest after his presentation. There seems to be little doubt in their result of reversing thymus involution and partial rejuvenation of the immune system. I just cannot get over how simple the protocol is. DHEA, rhGH, and metformin have been available for a long time...

To me Dr. Fahy’s work seems like a bright beacon of hope and one of the best things going in this arena. I was genuinely confused by the negativity generated on other platforms about this very small, very preliminary study. People criticized the study because the media over-reacted and sent up the hype fog.

Others criticized the study by saying never take rhGH under any conditions due to the risks. Fair enough. I agree unsupervised, sketchily-sourced human growth for home use sounds like a bad idea. But my understanding of Fahy’s study is that each of the ten subjects was treated and dosed individually based upon their own particular blood tests and MRIs. The rhGH was then targeted specifically to each person — individualized experimental medicine — to regrow the involuted thymus. And they evidently had success. Sounds encouraging, no? Since everyone on earth past childhood has a degenerating thymus...

Many also criticized the effort because of its small size. But the small number of subjects appears to be a funding issue. If they had more money they’d have worked with more people. Of course their work needs to be replicated in a way, way larger number of people, people of both genders and a wider age span of participants. But without money, what are they supposed to do? ...Gotta crawl before you stand, stand before you wobble and walk before you run and leap for stars of longevity; but I think this study is very encouraging, and one of the few real advances I’ve seen publicly announced.

[Nate-2004]

I talked to Dr. Fahy at RAADfest after his presentation. There seems to be little doubt in their result of reversing thymus involution and partial rejuvenation of the immune system. I just cannot get over how simple the protocol is. DHEA, rhGH, and metformin have been available for a long time. One would think that someone would have discovered at some point in the last few decades that taking these therapeutics in some combination resulted in some sort-of improving health markers.

 

Dr Fahy said that he did not have an answer for why this result has not been achieved or noticed previously, considering that thousands of people have taken growth hormone. He said the that the blunting of the insulin signaling pathway by DHEA and metformin  (while on growth hormone) must be the key to getting this positive result.

 

Because nobody is doing trials of synergistic substance protocols like this, except leaders in the rejuvenation industry. It's like nobody ever thinks of trying more than one thing. It's always "does this one single thing do what we want it to do?" As with treating and managing depression successfully, it's never any one thing.

Edited by Nate-2004, 26 October 2019 - 06:28 PM.

[TMNMK]

In the study they state 

 

Neither DHEA (Riley, Fitzmaurice, & Regelson, 1990) nor metformin are known to have any thymotrophic effects of their own.

 

 

 

However, on page 13 of this chapter DHEA Modulates Immune Function: A Review of Evidence they state:

 

Likewise, DHEA exposure protects against glucocorticoid-induced thymic involution and suppression of lymphocyte proliferation (Blauer, Poth, Rogers, & Bernton, 1991; May, Holmes, Rogers, & Poth, 1990)

 

 

Referencing a paper that came out in the same year coincidentally as the contradictory reference in the TRIIM study.

 

So maybe it is very dose, sex, and even species specific. And given the pleiotropic in-vivo effects tuning may be key. DHEA is quite a mess to untangle it would appear.

 

Perhaps growth hormone is needed for the results, but perhaps not!

Edited by TMNMK, 04 November 2019 - 02:37 PM.

[TMNMK]

One other really interesting finding of this study in case it was overlooked:

 

Analysis of CyTOF‐defined immune cell populations revealed the most robust changes to be decreases in total and CD38‐positive monocytes (Figure 4a, b) and resulting increases in the lymphocyte‐ to‐monocyte ratio (LMR) (Figure 4c).

 

Anyone following the NAD threads probably knows about CD38.

[Smith]

rgHG is easily obtainable as research chemical, DHEA is available OTC in the US, and metformin is available via prescription.  

 

Horvath clock blood tests are available on the Internet for as low as $299 (you'll need two of them, one before and one after). I suppose this protocol could be easy enough to test.  What's interesting is in months 9-12 of following the protocol, the researchers noticed the reverse aging effect accelerated to 6.5 year/year.

 

The rate of epigenetic aging reversal relative to chronological age accelerated from −1.6 year/year from 0–9 month to −6.5 year/year from 9–12 month. 

 

I'm just a bit surprised that such dramatic age reversal could come from three substances that are in wide use.  If these results hold up, it must be a synergistic effect between these three compounds.

Edited by Smith, 10 November 2019 - 10:14 PM.

[TMNMK]

Dr. Fahy discussion on this study 

 

[OP2040]

I totally disagree with this notion that “we would have known by now”. The reason we do studies is because everyday human experience is a very poor way of actually knowing anything. I take the rather extreme position that any one of these molecules could be the one that reversed the clock. Would something like Zinc go unnoticed as an anti-aging substance in humans? It absolutely could. Humans live for 80 years!!!

The crux of the issue here is whether epigenetic reprogramming will robustly extend life, aside from reversing aspects of aging. its entirely possible that you can reverse aging and not increase lifespan by one single day. Don’t get me wrong this would be a huge accomplishment. I’ll never understand why Belmonte didn’t continue his study to include lifespan.

[james freele]

From my experience of using topical zinc I would say it's very easy to consider everyone missed zinc as a key element. On a scale 1 to 10 zinc being difficult it's a 10 topical GDF 11 would be about a 4 not saying that it's easy but for using zinc for seven years 10 months I would say I got rid of 90% of all viral problems and the deeper stuff may take a lot longer.

[8bitmore]

From my experience of using topical zinc I would say it's very easy to consider everyone missed zinc as a key element. On a scale 1 to 10 zinc being difficult it's a 10 topical GDF 11 would be about a 4 not saying that it's easy but for using zinc for seven years 10 months I would say I got rid of 90% of all viral problems and the deeper stuff may take a lot longer.

 

What type of topical zinc are you using? And at what dosage? If at all possible I would really appreciate a product recommendation - or recipe as may be the case. Have family who's afflicted with lingering effects of Lyme's disease from years ago and ordinary oral zinc citrate (25mg) seems to have no beneficial effect even with prolonged intake.

 

Thanks,

[james freele]

Homemade solution out of zinc chloride. At what dosage I am a hacker trying to figure one particular problem . And noticed many other things are clearing up and it takes a while many years to bring these problems out . For about four years I had fibromyalgia symptoms after using it . That would've probably came up in my future . I'm 55 hormone started going wild when you hit the thyroid area but usually you get a sore throat and infection will start coming out . So hard way to fix yourself but a goal I have been doing that I have been working on for 11 years . And I learned a lot more than I tried to find out 11 years ago . I had all kinds of infection all over and I wasn't halfway decent shape . It can be very DANGEROUS the more infection you have and if it's been coming out to the surface of the skin for years it will burn almost instantly wash it off . (That's what I have been doing for almost 8 years very slowly it gets rid of viral problems ) I would never  want to suggest the amount that is individual to the person that wants to clear up problems and have a long hard track to correcting problems !!!!! 

[OP2040]

Some great comments James.  I am also a believer that viruses are a major unrecognized driver of ill-health and aging.  They are often implicated at the scene of the crime for both major classes of disease, degenerative and cancer.  Unlike bacteria, which we have learned to live and work with, and for which there are many classes of good, the evidence points to viruses being universally detrimental, outside of the contexts in which we control them for gene or phage therapaies.

 

The dream of course is to be able to have total control of the genome, meaning we can slice and dice viruses and transposons  to the point where not only can we eliminate them if we see fit, but actually turn them to our benefit when we can.  

 

Unfortunately for now, that dream is still down the road.  The best thing we can do now is have better testing so we know our own individual viromes, and to aid the immune system in suppression of it.

 

Like yourself, I've become more and more convinced that whatever is ailing me, it likely has a viral component.  Zinc is a wonderfully low-hanging fruit when it comes to helping suppress viruses. AHCC looks to be another with great potential.  Unfortunately, from a research-grounded perspective, that's all I got.  Of course, rejuvenating the thymus would help tremendously, at least theoretically.  and that brings us back to the potential of Zinc to be a possible unrecognized hero in the Trim study.

 

I could go on endlessly about viromes, transposons, their similarity an their increasingly obvious implication in one of the major causes of aging, genome stability.  Going on memory here, but one interesting factoid I recall is that the Sirtuin pathway works it's anti-aging magic in part by suppression of transposable elements.  One my wonder why I'm going on about transposons here.  Well, aren't they just viruses without a capsid?  And aren't viruses just foreign genetic material (transposons) with a capsid?  Leave aside for the moment the fact that in this evolutionary war, our bodies have been trained to use transposable elements in certain circumstances, like viruses it is very hard to find any redeemable quality in them.  It's possible that the entire evolutionary infrastructure built up around epigenetics is a counterbalance to these elements and their destructive impact on the genome.  

[james freele]

Regular zinc usage would be low hanging fruit. This is quite different I guarantee you that. What seems to be happening very slowly the zinc slot in the DNA gets filled because of the higher zinc orbital zn68 ions. Then when replicating the RNA picks up that signal and does not create broken proteins. Of course with the help of the body nuclear DNA bringing up to the right spot to fill that slot. That's what I'd hypothesize is happening.