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! 
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LukeMV
#30
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.
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Alex
#34
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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Jjazz
#37
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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DrT
#39
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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Since I am new to peptides I don’t have a deep understanding of them.
Maybe I made a rash assumption that including variations of “thymus” in the peptide name indicated it was good for treating thymus problems when they are only treating the immune system?
Some examples:
Thymosin Alpha-1
by Peptides.info Admin
December 24, 2020
Introduction
Formula: C129H215N33O55
Structure: Ac-Ser-Asp-Ala-Ala-Val-Asp-Thr-Ser-Ser-Glu-Ile-Thr-Thr-Lys-Asp-Leu-Lys-Glu-Lys-Lys-Glu-Val-Val-GluGlu-Ala-Glu-Asn-OH
Thymosin Alpha 1 (Tα1), is a polypeptide hormone produced by thymic epithelial cells, that can effectively increase T-cell numbers and support T-cell maturation. T-cells are a part of the immune system that focus on distinct foreign particles and responsible for immunity to foreign substances.
Thymosin is a hormone secreted from the thymus gland, an organ that plays an important function both in the immune system and endocrine system. Thymosin also aids in the growth of B cells to plasma cells to develop antibodies.
This is one of many peptide bioregulators that Professor Khavinson and his award-winning team at the St Petersburg Institute of Biogerontology have discovered
VLADONIX® - THE THYMUS PEPTIDE BIOREGULATOR.
Vladonix is a dietary supplement with natural thymus peptides. The thymus is responsible for the proper function of the immune system, which protects the body against diseases and potentially damaging foreign particles. High stress and unfavorable environmental factors have a profound effect on the immune system. If it is weak, it becomes much more difficult to deal with all diseases and as a result, quality of life considerably decreases.
There are are some others for example:
TB-500 / Thymosin Beta-4
TB-500, also known as Thymosin Beta-4, is a synthetic peptide derived from the naturally occurring thymosin beta-4 protein, which plays a role in cell migration, differentiation, and
regeneration. Dosing via subcutaneous injections; 2 to 10 mg/per week, divided into smaller doses throughout the week. Also available as Fragment oral capsules
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DrT
#42
Thanks for your detailed reply, DS.
Yes, I think that those peptides are either synthetic (based on the natural ones) or natural peptides derived from calf thymi. It seems they may have overall health benefits for the immune system but I’m not clear on the mechanism or details.
I’m trying to focus on any method(s) with any evidence of thymic rejuvenation. So far, Greg Fahy’s protocol looks good but there may be other ways to help, too. I’m still reading about Near IR light, small molecule unregulation etc.
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That product Vladox does not appear to rejuvenate the thymus, it looks like it’s designed to replace it’s function (“with natural thymus peptides”) and theoretically supply what the thymus has stopped producing. Based on what little I know about it, I’d have to read quite a bit more but from the basic description here that’s my first impression.
It sounds more like this example - testosterone replacement therapy TRT - doing that (TRT), is not “fixing” the root cause, it’s replacing the result of impairment in the root cause. In doing so it further impairs the functionality of the testes.
So I just started using gonadorelin instead. I’m early in this process of figuring out if there are better options but it’s a first step to see how that one goes 
I may change that down the road.
I use TB500 every day, in combination with BPC157 - TB500 does not repair the thymus, again it’s more like a replacement therapy. 500mcg each in one injection. Its often called “wolverine blood” in the sports world for this combinations potent healing abilities.
Both those peptides are “healing” peptides and work synergistically on a couple levels. One is a VEGF producer and the other is a VEGF receptor. So BPC increases the production of VEGF and TB500 stimulates the cells receptors of VEGF. This process enables angiogenesis, which is one of those 2 edged sword things There are other beneficial things happening with both those peptides though, this is just one of their activities.
My objective in this whole process of trying to deal with the process of aging is to try and address root causes and get the body to produce and use the things it needs to be healthy. This may not be possible for some things and only RT (replacement therapies) will work.
Which is why for HGH I don’t use Somatropin, I use secreteagogues that tell the hypothalamus and pituatary gland to get back to work and do their job, at the right time of day or in this case night.
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Thank you that is very helpful.
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I would argue that its too early to say that this has been “demonstrated”. Small sample size in the first trial, and Eric Verdin is suggesting results from the bioclocks may be an artifact…
Eric covers the issue in this presentation:
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There is older information available on the beneficial effect of HGH on the thymus, probably what spurred this study.
The small sample size is a concern.
If epigenetic results were the only measurement used, I’d agree with Verdin on that possibility. Not sure why Verdin would ignore the other results. Since Steve Horvath was also involved in this study, I’d hope that his expertise would have kept the epigenetics relevant but who knows for sure? Maybe Horvath is off track on this one? it’s possible.
But since other measurements were also used, I feel that “demonstrated” is still a relevant way to describe the results from the non-epigenetic measurements used in the first study.
I am looking forward to seeing the results from the TRIIM-X study.
I remain hopeful on this one as both my wife and I have seen positive changes in our immunosenescence since starting this little experiment. Although it is epigenetic evidence, so could easily be questioned and an N=2 is proof of nothing
2.2. Thymic and bone marrow regenerative responses
Obvious qualitative improvements in thymic MRI density were observed and are illustrated in Figure Figure2.2. Quantitatively, the overall increase in the thymic fat‐free fraction (TFFF) was significant at the p = 8.57 × 10−17 level based on linear mixed‐model analysis, implying a restoration of thymic functional mass. The improvements were significant in 7 of 9 volunteers (Figure (Figure3a–c).3a–c). Two volunteers had abnormally low levels of thymic fat (high TFFF) at baseline, and their TFFFs did not significantly improve with treatment (peak relative changes of +9.6% (p > .3) and +12.4% (p > .2);
2.3. Immune cell subset and cytokine changes
Analysis of CyTOF‐defined immune cell populations revealed the most robust changes to be decreases in total and CD38‐positive monocytes (Figure (Figure4a,4a, b) and resulting increases in the lymphocyte‐to‐monocyte ratio (LMR)
Older information on HGH and the thymus.
https://onlinelibrary.wiley.com/doi/pdf/10.1046/j.1365-3083.2002.01077.x
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jnorm
#47
Moreover, we found that the absolute cell number of TECs decreased significantly after RPM treatment… the cell number of mTECs decreased significantly whereas the cell number of cTECs had no change after RPM treatment (P <0.001, Figure 1H), indicating that RPM treatment selectively impacts mTECs in mice.
Adult thymic epithelium exibits low turnover (i.e thymic epithelial progenitors are relatively quiescent, e.g Multilineage Potential and Self-Renewal Define an Epithelial Progenitor Cell Population in the Adult Thymus), so the reduction in TEC count they observed with rapa maybe isn’t due to slower cell cycling/division (obviously, reduced cell size, the hallmark of mTORCi also fails to explain reduced TEC count, although it could partially explain reduced thymus weight).
My worry is that rapa affects thymic involution via TGFB-activation (woefully under recognized rapa off-target that I’ll make a separate post about soon). The thymic transcription of this factor increases with age in humans and mice (protein levels also shown to increase in aged mice), and ablating its receptor TGFBR2 in mice TECs mitigates loss of TEC count with aging while increasing proliferation (TGFB also reduces in vitro proliferation of TEC cell lines). While reduced cell cycling might explain the reduced proliferation, the concern is that it’s due to loss of self-renewal in the progenitor cells.
Data from TGF-β signaling in thymic epithelial cells regulates thymic involution and postirradiation reconstitution
Aged thymic cells also exhibit features of epithelial-to-mesenchymal transition (see Age-related epithelial defects limit thymic function and regeneration), which is a process regulated by TGFB. Rapa can also induce EMT in a TGFB-dependent manner (see Rapamycin activates TGF receptor independently of its ligand: implications for endothelial dysfunction).
We applied single-cell and spatial transcriptomics, lineage-tracing and advanced imaging to define age-related changes in nonhematopoietic stromal cells and discovered the emergence of two atypical thymic epithelial cell (TEC) states. These age-associated TECs (aaTECs) formed high-density peri-medullary epithelial clusters that were devoid of thymocytes; an accretion of nonproductive thymic tissue that worsened with age, exhibited features of epithelial-to-mesenchymal transition and was associated with downregulation of FOXN1. Interaction analysis revealed that the emergence of aaTECs drew tonic signals from other functional TEC populations at baseline acting as a sink for TEC growth factors.
Age-associated thymic adiposity might then be explained by adipocyte transdifferentiation of EMT-derived mesenchymal cells, but that’s not really the concern here.
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