Thymus health

Mauritio

Peat has often talked how important thymus health is and how in old people the thymus is often non existent anymore due to stress.
Here's a few strategy's to fix it:

Vitamin B3 rescues thymus weight by increasing NAD+ and Sirt6. Also prevents hepatosteatosis.
https://pubmed.ncbi.nlm.nih.gov/28536482/
The number of serotonin synthesizing cells in the thymus increased as we age. I wouldn't be surprised if there was a causative relationship here.
https://pubmed.ncbi.nlm.nih.gov/19827686/
This study shows causative relationship on serotonin causing thymus involution.

"Administration of serotonin or 5-HTPH causes a marked reduction of the thymus weight. It is reasonable to postulate that the described effects result from the thymus involution..."
https://pubmed.ncbi.nlm.nih.gov/6967931/

T4 can stop thymus involution and be anabolic to it, even at old age.

"...thymuses from T(4)-treated aged mice revealed that the cortex was preferentially enlarged and repopulated with immature thymocytes. "https://pubmed.ncbi.nlm.nih.gov/16684146/

Zinc deficiency can cause thymus atrophy.
https://pubmed.ncbi.nlm.nih.gov/20860857/
Spermidine and even more so Spermine stop glucocorticoid induced thymus apoptosis.
https://pubmed.ncbi.nlm.nih.gov/1649056/

DavidPS

@Mauritio - Another interesting topic. Magnesium may also be needed to keep the thymus healthy.
Accelerated thymus involution in magnesium-deficient rats is related to enhanced apoptosis and sensitivity to oxidative stress

Mauritio

@DavidPS makes sense since it's so anti cortisol .

Mauritio

COVID destroys the thymus gland. The thymus expresses ACE2 which facilitates viral entry, so ACE2 inhibitors might help here.

Also interesting that disease severity correlated with thymus atrophy.

https://pubmed.ncbi.nlm.nih.gov/36758836/

yerrag

@Mauritio said in Thymus health:

COVID destroys the thymus gland. The thymus expresses ACE2 which facilitates viral entry, so ACE2 inhibitors might help here.

Also interesting that disease severity correlated with thymus atrophy.

https://pubmed.ncbi.nlm.nih.gov/36758836/

Could it be that very often the first line of treatment in respiratory distress involves the use of Budenoside, or cortisol, in respiratory therapy? And cortisol weakens the immune system by reducing the size of the thymus gland?

cs3000

@Mauritio

Also interesting that disease severity correlated with thymus atrophy.

yeah , first thought might think the lowered immune cells from their atrophied thymus would create less damage & be beneficial. but neutrophils can rise to an extreme to do that which come from bone marrow and lack of T-Reg cells coming from the thymus might worsen that

(might be why you see elevated neutrophil:lymphocyte ratio in health problems https://pmc.ncbi.nlm.nih.gov/articles/PMC2999808/ atrophied thymus? which intuitively isnt the place you'd look to to help an autoimmune problem https://www.nejm.org/doi/full/10.1056/NEJMoa2302892 When patients with a preoperative history of autoimmune disease (e.g., myasthenia gravis) were excluded, the number of postoperative autoimmune diseases per patient was still higher in the thymectomy group than in the control group (1.7 vs. 1.2

Looks like the main benefit of the Thymus could actually be from suppressing too much immune damage via t reg cells
https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1339714/full
https://pubmed.ncbi.nlm.nih.gov/33537838/

The pathologies of several autoimmune conditions, such as type 1 diabetes, rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus and myasthenia gravis (MG) are based on dysfunctional Tregs
{t cells have to dysfunctionally clone peripherally if not coming from thymus?}
The removal of the thymus (i.e. thymectomy) in mice at the age of 3 weeks was shown to lead to the development of autoimmunity (180)
.

another one, 6% protein calories vs 20%
4 calories in 1 gram of protein
at 2500 calories human equiv ~35grams daily gave a way smaller thymus vs 125grams protein daily with extra carbs replacing the lost protein,

87% lower thymus weight from 35g protein daily

The wet weight (g) of the thymus and mesenteric lymph nodes decreased due to protein malnutrition by 87% (from 0.30 ± 0.05 to 0.04 ± 0.01) and 75%
(0.40 ± 0.04 to 0.10 ± 0.02), respectively
Effect of protein malnutrition on the glycolytic and glutaminolytic enzyme activity of rat thymus and mesenteric lymph nodes

doesn't mean the higher intake is needed tho, maybe stable point for protein intake is ~ double that low end

In the absence of thymic control, the B cells are still able to produce antibodies, but they are more likely to produce autoantibodies.
The thymus was noted to be "a barometer of malnutrition, and a very sensitive one" (2). The size and weight of the thymus are reduced.

looking into Koch's info on immunity without needing immune cells so much http://www.williamfkoch.com/

Mauritio

@yerrag yeah right and didn't they give cortisone to calm the cytokine storm for COVID ?

Mauritio

@cs3000 said in Thymus health:

Looks like the main benefit of the Thymus could actually be from suppressing too much immune damage via t reg cells

That is such an interesting thought. Why wouldnt we have an organ whos purpose it is to dampen excessive inflammation, given chronic inflammation is a part of so many diseases.

yerrag

@cs3000 said in Thymus health:

might be why you see elevated neutrophil:lymphocyte ratio in health problems

I always have high neutrophil:lymphocyte ratio 70:20 but have very good immunity, being very resistant to respiratory diseases such as the flu (and COVID) but maybe this keeps my acquired immune system from being overactive;

but my chronic low grade infection and my having heavy metal toxicity disposes my phagocytic cells (neutrophils and macrophages) to be overactive, and my immune system always being on an alert state helps keep my immune system primed;

but this seem to have a downside as an underactive acquired immune system seems to make me develop more cysts and keloids where the inability of my lymphocytes to kill certain microbes makes the body develop fibrous walls to isolate and wrap these microbes and form cysts, but these cysts are benign though

yerrag

@Mauritio said in Thymus health:

@yerrag yeah right and didn't they give cortisone to calm the cytokine storm for COVID ?

was it to calm the cytokine storm as a way to dampen Inflammation? I just know cortisone is used as an anti-inflammatory but don't know the mechanism.

Mauritio

@yerrag not sure.

Johann2547

And IIRC theanine is beneficial for the thymus.

yerrag

@Johann2547 said in Thymus health:

And IIRC theanine is beneficial for the thymus.

interesting thread. makes me think the thymus, being where t cells mature, gets to have a sizable impact on how our immunity functions, or dysfunctions

For one, it dampens the inflammatory response of the innate immune system, characterized by the heavy involvement of neutrophils and macrophages where phagocytic activity can result in a large amount of collateral peripheral tissue damage from spillover ROS.

And given that the lack to T cells can result in B cells exerting more immune response, the tendency of B cells to generate autoimmune responses is also problematic.

Seems to me that ensuring we have a healthy thymus favoring the calming and moderating influenxe of T cells is not a small matter, and that metabolic health, where the stress hormone has to be kept to a minimum level of production and influence can never be stressed, pun not intended, enough.

I can't help but think of metabolic health being as impactful on our immunity, and this is is but just one example of Ray's dictum that metabolic health drives all other aspects of health in us.

I know I have a very rudimentary understanding of immunity, and I'm just giving an immaturely formed rambling of what I can gather from the musings of @mauritio and @cs3000 and @DavidPS

Please let me know how far off I am and what more you can detract and add to it

DavidPS

@yerrag - I have never studied any of the biological sciences. But as I get older each year, I am increasing interested in healthspan and mindspan. As far as I can determine, your remarks are spot-on.

I am waiting for the results of the TRIIM-X trial (Thymus Regeneration, Immunorestoration and Insulin Mitigation) mentioned in this paper.

Immune tolerance and the prevention of autoimmune diseases essentially depend on thymic tissue homeostasis

yerrag

@DavidPS

Thanks David. Looks interesting, but very deep and I wish my mind can ensure the onslaught of very unfamiliar words when reading on immunity down to deep levels.

I am reminded of what Peat had said before about T cells- that if you have a good T-cell response, you really won't need to rely on B-cells for immune protection as much. It is like saying a B-cell response is optional when T-cells are involved in the response. I remember him talking or writing about this at the start of the CoVID years. And in the ensuing two years marked with headlines about COVID, all I could hear was centered on B-cell immunity and ntibodies, centered on viral therapeutics.

The funny thing is that the elephant in the room was always being ignored, in the absence of the mention of the T-cells, such that its importance was being downplayed. It seemed to me the medical response is to trivialize the importance of T-cells to improving our body's response to the putative virus.

I think that beefing up the thymus gland should be the main topic of the COVID response.

cs3000

@Mauritio said in Thymus health:

@cs3000 said in Thymus health:

Looks like the main benefit of the Thymus could actually be from suppressing too much immune damage via t reg cells

That is such an interesting thought. Why wouldnt we have an organ whos purpose it is to dampen excessive inflammation, given chronic inflammation is a part of so many diseases.

@yerrag said in Thymus health:

The funny thing is that the elephant in the room was always being ignored, in the absence of mention of the T-cells, such that it's importance was relegated to that of a bit player, inconsequential to improving our body's response to the putative virus.

Seems to me that beefing up the thymus gland should be the main topic of the COVID response. The question of the day.

Looks like a big health unlock , neutrophils are big players in autoimmune problems maybe the biggest, you see them showing up causing big damage in a wide range of health issues covid cystic fibrosis ulcerative colitis heart failure etc

and theyre highly destructive with different weapons, cytokine release, then they have proteases that degrade the structure surrounding the cell (if u inhibit neutrophil proteases in arthritis they dont develop arthritis at all https://pmc.ncbi.nlm.nih.gov/articles/PMC150852/ ), and they can form wild traps where they basically gut themselves & spill out strands of dna laced with proteins to form damaging webs like some kind of arsehole spiderman in the autoimmune situation

their benefit is mainly in the first 12 hours where theyre supposed to help kickstart the cleanup & repair process then back off (reversing their path back into bone marrow). but in the current state of health its common that they stay chronically activated for days weeks months years . regulatory t cells specifically T Reg cells look key to help resolve that

@yerrag I can't help but think of metabolic health being as impactful on our immunity, and this is is but just one example of Ray's dictum that metabolic health drives all other aspects of health in us.

something that fits with that & the rest, neutrophils dont use mitochondria for energy they basically just use glycolysis (& can create their own glucose in presence of glutamine too, and use fatty acids for some functions like ROS production or possibly switch over to fatty acid use to become more intense, in my experience eating more fat takes high neutrophil damage to an extreme),
BUT unlike neutrophils T Reg cells need mitochondria complexes functioning to enable their immune resolving function

yerrag

@cs3000 said in Thymus health:

Looks like a big health unlock , neutrophils are big players in autoimmune problems maybe the biggest, you see them showing up causing big damage in a wide range of health issues covid cystic fibrosis ulcerative colitis heart failure etc

and theyre highly destructive with different weapons, cytokine release, then they have proteases that degrade the structure surrounding the cell (if u inhibit neutrophil proteases in arthritis they dont develop arthritis at all https://pmc.ncbi.nlm.nih.gov/articles/PMC150852/ ), and they can form wild traps where they basically gut themselves & spill out strands of dna laced with proteins to form damaging webs like some kind of arsehole spiderman in the autoimmune situation

There is a lot I don't understand about the adaptive immune system and maybe it's this lack of understanding that betrays my view in seeing autoimmunity to be largely involved with B-cells.

In this regard, autoimmunity is not so much different from being very sensitive to stimulus that the immune system wrongly regards something that is endogenous as being foreign.

I have chronic high blood pressure and it is the result of my neutrophils and macrophages of the innate immune system trying to get rid of heavy metal toxins and periodontal infections with no success, given the persistency of these insults where they don't get permanently removed or killed. It is like Groundhog Day for my immune system where they keep repeating their efforts to get rid of persistent insults that keep bouncing back. Yet I do not consider the inflammatory effects of this endless effort to be an autoimmune condition. But I blame the tenacity of heavy metals refusing to be swallowed up and excreted out, and the ability of synergistic bacteria and fungi to defend against attack by phagocyte activity by neutrophils and macrophages.

But lately I have used techniques and substances to assist my immune system to successfully get rid of the hitherto unremovable toxins and immortal infection. But I had to employ medically unorthodox techniques to achieve these.

Seems to me medical complex is guilty of spreading misinformation and disinformation to label as autoimmune, on the strength of their vaunted research which are in many cases made up stories to lead trusting souls astray.

Yet I do not wish to throw the baby with the bathwater, for a large part of the body of research is valid, and a good filter is needed to separate wheat from chaff.

Lejeboca

@yerrag said in Thymus health:

was it to calm the cytokine storm as a way to dampen Inflammation? I just know cortisone is used as an anti-inflammatory but don't know the mechanism.

Below is a study that considers the dual pro- and anti-inflammatory effects of cortisol under stress with respect to the time of introduction of immune challenge (LPS), It also notes the mechanism of upregulating TLRs, which recognize pathogen molecular patterns, in the brain and liver.

Prior exposure to glucocorticoids sensitizes the neuroinflammatory and peripheral inflammatory responses to E. coli lipopolysaccharide

Abstract

Acute and chronic stress has been found to sensitize or prime the neuroinflammatory response to both peripheral and central immunologic challenges. Several studies suggest that stress-induced sensitization of neuroinflammatory processes may be mediated by the glucocorticoid (GC) response to stress. GCs, under some conditions, exhibit pro-inflammatory properties, however whether GCs are sufficient to prime neuroinflammatory responses has not been systematically investigated. In the present investigation, we tested whether acute administration of exogenous GCs would be sufficient to reproduce the stress-induced sensitization of neuroinflammatory responses under a number of different timing relationships between GC administration and immune challenge (lipopolysaccharide; LPS). We demonstrate here that GCs potentiate both the peripheral (liver) and central (hippocampus) pro-inflammatory response (e.g. TNFα, IL-1β, IL-6) to a peripheral immune challenge (LPS) if GCs are administered prior (2 and 24 h) to challenge. Prior exposure (24 h) to GCs also potentiated the pro-inflammatory response of hippocampal microglia to LPS ex vivo. In contrast, when GCs are administered after (1 h) a peripheral immune challenge, GCs suppress the pro-inflammatory response to LPS in both liver and hippocampus. GCs also up-regulated microglial activation markers including Toll-like Receptor 2. The present data suggest that the temporal relationship between GC treatment and immune challenge may be an important factor determining whether GCs exhibit pro- or anti-inflammatory properties.

Although the study considered a pretty high dose of cortisol (CORT), smaller (and chronic) doses would have a similar effect, in its nature, *the authors fixed the measurements at 4h of LPS introduction.

A dose of CORT was chosen that had previously been determined to mimic the plasma CORT proﬁle produced by an acute stressor (a session of 80–100 inescapable tailshocks) (Fleshner et al., 1995). We had found that this acute stressor potentiates the neural and peripheral inﬂammatory responses to LPS administered 1–4 days later (Johnson et al., 2002).

Lejeboca

This got me thinking that, since our endogenous CORT is "naturally" elevated in the morning, if we have an LPS-prone breakfast, then any existing inflammation will spike.
So

rule #1, breakfast that is easy on digestion (Ray-Peat-right-again!)
At breakfast time consider
charcoal or anything digestion-promoting
getting red/sun light at breakfast time to to decrease NO and other inflammatory cascade factors.

DavidPS

The gut microbiome and the intestinal barrier are involved as well.

Age-related loss of intestinal barrier integrity plays an integral role in thymic involution and T cell ageing (2024)