#21

RapaAdmin has posted about this several times : Since mice have a roughly 12x higher metabolic rate than humans, to achieve the same plasma or tissue concentration of a drug, the daily dosage/kg (body weight) needs to be 12x higher in mice than humans. Also the frequency of dosing needs to be 12x more frequent in mice (eg Rapamycin daily dosing in mice corresponds to every 12 day dosing in humans). (This means that each dose/kg is the same in mice and humans). Daily dosing in humans corresponds to dosing every 2 hours in mice, which is often approximated by mixing the drug into the mouse food or water. In this case they used once daily dosing for mice, which is unusual.

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#22

Thank you @tananth for bringing this to my attention, it’s much appreciated.
It’s so easy to keep increasing the dose of a drug without thinking about what the maximum dose is.
Seriously I will think about cutting back my metformin dosage.

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#23

blsm, It’s been a while since you made this post, but it’s an interesting thought. If cooked I assume any useful ingredients would be destroyed and if not cooked it would be out of the question for me. However, many people use dessicated pig thyroid for hypothyroidism. Why couldn’t the companies that do this processing consider processing the thymus gland the same way? Of course, I’m sure they would have to have sound medical backing to pursue that. But, gee, wouldn’t that be a way to bypass the thymus rejuvenation approach?

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#24

Thymus gland extract are destroyed by the digestive tract and would have to be purified and injected (like Insulin). However, one company makes one long Thymus protein (Proboost Thymic Protein A, $90 for 60 days supply, with subscription discount) and claims it is absorbed, if taken on an empty stomach. I have been taking it daily in the winter (when immune system needs to be boosted the most), and every other day in the summer (to save money). Not sure if it actually works.

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#25

I would have thought that perhaps implanting some stem cells or induced pluripotent cells into the thymus might yield results but I’ve never heard of anyone doing it. Or perhaps extracting a few viable thymus cells, culturing them in vitro, then injecting them back into the patient? Any comments from researchers in the stem cell area welcome.

#26

DrT, Interesting ideas. Why not? But, I wonder if whatever is causing the natural Thymus involution would affect the implanted cells the same way?

#27

By the way, it seems that Bryian Johnson has discontinued Dr. Fahey’s protocol, after having seen the negative results on him (in terms of epigenetic clocks I presume).
I remember he called it a ‘Whackamole’.

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#29

But he did say it shrank his thymus, so it wasn’t all bad.

#30

I don’t remember that, probably I construed it to be negative (shrinked = atrophied thymus).

If I’m right, Dr. Fahey says the involved thymus has less active tissue and more adiposity in it. His therapy is supposed to reverse this process.

#32

Lvareilles, pls note I’m not competent in the medical field let alone in the specific camp of this very little-known organ.
I just went back to some interviews with Dr. Fahey and one in particular. He speaks about ‘thymus involution’ and then ‘thymus regeneration’. I have no personal opinion, my mind just automatically tries to configure every input into a logical framework.
I’m going to paste an excerpt from Dr. Fahey. He seems to speak of thymus shrinkage in this old rat in negative terms.
Of course, the same definition can have a dual meaning, like shrinkage is good when it is a sign of lack of edema or bloated issues…
My interest in this protocol was potential benefits to either longevity and connective tissues, since I cannot lift heavy because of tendon pains. But it appears to be controversial, besides HGH is overly expensive.

If you continuously expose an old rat to growth hormone the incredibly deteriorated thymus, which looks nothing like a normal thymus both histologically and physically, the thymus actually shrinks down to a size that was so small that they couldn’t even weigh it. In the study it looks like a glob of fat but you can still bring that thymus back by giving the animals cells that secrete growth hormone (constitutively pituitary adenoma cells in particular), they found that when they did that not only did the thymus come back to its normal morphology, but T-cell ability to respond to foreign antigens was restored back to the level seen for a three-month-old rat. That caught my attention.

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#33

My apologies. I posted that early this morning before my brain could kick in. Thymus shrinkage happens with aging, so yes it’s indeed a bad thing. No idea how I typed the opposite :man_facepalming:

The TRIIM trials are regrowing the thymus

I’m also very interested in all this and have listened to most of Greg Fahy’s talks and interviews about it.

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#34

LOL, no problem whatsoever, I can’t say I’m always fully awake myself!

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#35

Dr. Greg Fahy discusses his groundbreaking research on thymus regeneration, immune system rejuvenation, and the role of growth hormone, DHEA, and metformin in reversing aging-related immune decline. He explains the TRIM protocol, the impact of thymic involution on longevity, and the potential for improving vaccine response and overall health. This conversation explores immune function, senescent cell clearance, and epigenetic aging clocks.

0:00 - Introduction & Guest Introduction
2:05 - The Origins of the TRIM Protocol
6:30 - Growth Hormone & Thymus Regeneration in Rats
12:40 - Growth Hormone, Insulin Resistance & DHEA
20:10 - Why Thymus Regeneration Matters for Longevity
27:50 - Thymic Involution & Its Role in Aging
35:45 - Measuring Thymic Function & Immune Rejuvenation
42:15 - Rapamycin, Thymus, and Immune System Enhancement
50:20 - Human Trials: Thymus Regeneration & Exercise Performance
1:03:00 - The Future of Anti-Aging & Immune Restoration

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#36

AI generated summary, warning, it may contain omissions and inexact data.

Here’s a summary of the discussion between Dr. Matt Kaeberlein and Dr. Greg Fahy, focusing on the key points:

  • Trim Protocol & Thymus Regeneration
    • Dr. Fahy became interested in thymus regeneration around 1990 after a study on rats showed thymus regrowth was possible [00:54].
    • The trim protocol aims to regenerate the thymus, which typically involutes (atrophies) with age [18:34].
    • The original trim protocol involves a combination of growth hormone, DHEA, and metformin [15:05].
      • Growth hormone helps regrow the thymus [09:19].
      • DHEA helps counteract the insulin resistance caused by growth hormone [10:36].
      • Metformin provides additional support in mitigating the hyperinsulinemic effect [15:30].
    • Thymic involution involves the loss of functional thymic mass and its replacement with fat [18:46].
    • Regenerating the thymus involves eliminating fat and replacing it with functional thymic cells [18:54].
    • MRI is used to visualize and measure thymus regeneration [19:26].
  • Importance of the Thymus
    • The thymus is crucial for producing new T-cells, which are essential for the adaptive immune system [25:44].
    • Thymic involution leads to a decline in immune function, increasing the risk of infections, cancer, and autoimmune disorders [24:46].
    • A study showed that removing the thymus in adults increased the risk of death, cognitive decline, cancer recurrence, and more aggressive cancer [23:27].
  • Measuring Thymic Function
    • Thymic function is assessed by measuring the levels of naive T-cells (CD4 and CD8) in the blood [35:04].
    • Recent thymic immigrants, a very early form of T-cells, can also be measured [36:09].
    • Dr. Fahy’s initial research indicates that the T-cell changes observed are equivalent to reversing immune system aging by 10-20 years [35:36].
  • Human Studies & Results
    • Dr. Fahy conducted a self-experiment to regrow his own thymus [10:07].
    • Human studies have shown that the trim protocol can regenerate the thymus and improve immune function [30:41].
    • Participants in the studies have shown improvements in muscle strength, exercise capacity (VO2 max), and other physiological markers [52:19].
    • The benefits of the trim protocol may include a reduction in senescent T-cells [49:06].
  • Future Directions & Considerations
    • Future research will focus on optimizing the trim protocol and exploring new ways to regenerate the thymus [01:07:53].
    • Dr. Fahy is exploring ways to increase IGF-1 levels without high doses of growth hormone to reduce costs [01:09:07].
    • The long-term effects and potential for repeated cycles of thymus regeneration are being investigated [01:21:01].
    • The role of sex hormones, particularly testosterone, in thymic involution is discussed [01:26:04].
    • Dr. Fahy is seeking funding for larger, placebo-controlled clinical trials [01:19:03].

Would you like to explore any of these points in more detail?

Here is what was discussed about rapamycin in the video:

  • A study by Pen Jang from Michigan showed that short-term treatment with rapamycin boosted flu vaccine response in mice [41:33].
  • Rapamycin is really bad for the thymus, depleting it of lymphocytes and blocking T-cell maturation [43:17].
  • The shrinkage of the thymus was reversible with rapamycin. When they stopped rapamycin, it came back [47:12].

Would you like to explore any other points from the discussion?

Based on the discussion, rapamycin is bad for the thymus in the long term, causing it to shrink by depleting it of lymphocytes and blocking T-cell maturation. However, this shrinkage is reversible; the thymus can recover when rapamycin treatment is stopped.

Would you like to explore any other points from the discussion?

Yes, the video does discuss intermittent rapamycin dosages. Here’s a summary:

  • It’s mentioned that rapamycin is really bad for your thymus [01:44:02].
  • At doses equivalent to therapeutic doses for organ transplant patients, rapamycin depletes the thymus of lymphocytes and blocks T-cell maturation [01:44:02].
  • The conversation shifts to lower, intermittent doses, such as 6 milligrams once a week, and questions what effect that might have [01:44:19].
  • The effect of inhibiting mTOR, which rapamycin does, varies depending on the dose and whether it’s chronic [01:46:13].
  • The thymus shrinkage caused by rapamycin is reversible when the treatment is stopped [01:47:12].
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