Rapamycin Accelerates Thymic Involution in Mice

Thymus MRI is going to expensive and, as you suggested, not covered by insurance. A blood test that measures circulating naive T cells would be a more practical readout that would reflect thymus function. Something like this:

https://www.mayocliniclabs.com/test-catalog/overview/89319

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I know that Rapamycin suppresses T-cells, that’s why it’s used in transplants. Wondering if it also affects thymus.

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The immunosuppressive effects of rapa are generally attributed to suppression of peripheral T-cell activation and proliferation, rather than from a reduction in naive T cell output from the thymus. The latter correlates directly with thymus size/involution while the former does not. There is going to be a lag, however, between any rapid thymus involution and naive T cell numbers in the periphery. So imaging might be ideal even if not very practical.

Hopefully a clinician will chime in.

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As rapamycin inhibits cell division it is likely to affect cell production from the Thymus as well.

One of the issues with thymic involution is that the thymus matures and “curates” T-cells.

The T-cells produced by bone marrow are screened/matured by the thymus, and only 3% of the ones produced are allowed to enter the immune system.

Because there are good and bad T-cells.

Without the thymus screening new T-cell production (thymic involution), the harmful T-cells can increase in volume and contribute to auto-immune diseases.

This is why the TRIIM and TRIIM-X trials and protocol is so important to longevity. An immune system that does not make you sick is important.

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Once you hit 40 and for many even earlier, the thymus is all done doing it’s job.

TES starts decreasing from the first year of life at a rate of 3% until middle age (35–45 years of age), whereupon it decreases at a rate of 1% until death.[6] Hypothetically, the thymus should stop functioning at around 105 years of age;[10] but, studies with bone marrow transplant patients have shown that the thymi of the majority of patients over forty were unable to build a naïve T cell compartment

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It strikes me as possible that this is part of aging as is (probably) puberty and menopause.

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Agreed, evolution only cares about 1 thing, continuation of the species.

Once we pass breeding age, evolution has no interest in keeping us alive or functional.

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Damn that bastard evolution!!!

All it cares about is sex! :wink:

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We might be the only two people here doing our TRIIM trials. Good to know I’m not the only one.

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This is from my last Tru test. This would be early in my TRIIM process. I had been using; 1) a glucose control peptide and 2) GH secretagogues from July 2023 on and added 3) the DHEA in January 2024. So only about 2 months of the “full” program at the time of this particular test in Feb 2024. I’ll be doing this same test again in September and that will give me 9 months on that protocol to see how it’s going.

Under 1 is bad, not sure if higher than 4 (mine is 6.07) is good or bad. A couple years ago I had some weird things going on and my GP sent me to a Rheumatologist for testing on my immune system. They gave me a clean bill of health on that aspect.

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These studies seem to suggest the effect is reversible, which for me highlights that it will be important to pulse the dose and take rapamycin holidays.

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The effect on the thymus is only reversible with the TRIIM protocol. Thymic involution is a “natural” process that we all are experiencing and starts as early as 1 year of age.

Here is a discussion on the possibility of 2 phases in thymic involution.

One of the most acknowledged changes of the aging immune system is regression, or involution of the thymus, which seems to occur in almost all vertebrates suggesting that this is an evolutionary ancient and conserved process. Age-associated thymic involution involves a decrease in tissue mass and cellularity, together with a loss of tissue organization with the net outcome being a reduction in naïve T cell output. This decline in naïve T cell output is believed to have a major impact on the properties on the peripheral T cell pool such that with increasing age, these cells exhibit alterations in phenotype and function, loss of diversity, and replicative senescence. Moreover, it is these age-related changes in peripheral T cells that are believed to contribute significantly toward the features of immunosenescence suggesting that the altered thymic activity is a key trigger toward the decline of immune function in the aged.

Ok, I admit I do not know what a TRIIM protocol is. Could you please explain that? Thanks.

I think peptides will be the next big thing. As you know, several peptides claim to rejuvenate the thymus.

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Really? The article posted by Jjazz references a study that show spontaneous reversal of rapamycin induced thymic involution. Nothing about TRIM or TRIM-X or the use of other molecules - just time, 10 days of no rapamycin.

Results

Thymocyte respiration (µM O2 min−1 mg−1) was reduced by sirolimus and everolimus (p ≤ 0.007). In contrast, the dual PI3K (phosphatidylinositol-3-kinase)/mTOR inhibitors BEZ235, GDC0980 and GSK2126458, the highly-selective PI3 K-p110-δ inhibitor idelalisib and the calcineurin inhibitor tacrolimus had no effects on thymocyte respiration. Sirolimus was administered intraperitoneally on Days 0–3 and the thymus was then examined on Days 4 and 14. Cortex involution associated with increased cytochrome c and caspase-3 positive cells (apoptosis) were observed on Day 4; these changes were resolved on Day 14 (10 days after sirolimus treatment). On Day 4, the residual thymus (mostly medulla) had normal cellular respiration, decreased caspase activity and increased glutathione. Intraperitoneal administration of sorafenib (a multikinase inhibitor) or idelalisib had no effects on thymus size.

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Yes, it is encouraging that this group saw reversal within 10 days. But remember that this was only a one time, three day treatment. We shouldn’t assume that reversal will also occur in a human after years of weekly dosing, with or without drug holidays. It may or may not. Someone really needs to look into this in one of the ongoing human trials.

That looks like a mouse study “Intraperitoneal administration” is not typically used in human studies.

Note that the thymus does not “make” T-cells, it maturates them as they are produced by the bone marrow. In that process it also curates them so they are beneficial. The bone marrow continues to produce T-cells but as the thymus involutes, the maturation and curation process is not as robust and eventually becomes non-functional.

Here is a great explanation of the thymus, how it works, why it is important, and why it’s a good idea to try and revive it as we age.

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Hi DS,

My searches have failed to turn up much in the way of peptides involved in rejuvenation of the thymus. Thymus peptide preparations (from calves) are sold commercially in an attempt to boost immune system function. Do you mean these peptides?

The only peptide I’m aware of is either HGH secretagogues or Somatropin that have an effect in the thymus, with some help from 2 other compounds.

The TRIIM and TRIIM-X protocols have demonstrated thymic rejuvenation using Somatropin, Metformin and DHEA

I’ve posted my version of that and that I started it

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