Inflammation drives impairment of hematopoietic stem cell self-renewal and accelerated aging

This study is interesting to me, because it seems to bring together two areas of rapamycin research: Rapamycin’s well-known anti-inflammatory benefits with the benefits in terms of slowing or stopping aging of hematopoietic stem cells as shown in the Nov’21 report below.
See: Rapamycin Prevents Blood Stem Cell Aging, New MIT Study

Inflammatory exposure drives long-lived impairment of hematopoietic stem cell self-renewal activity and accelerated aging

Highlights

• HSCs fail to recover functional potency after inflammatory/infection challenge

• Discrete challenges have a cumulative effect, even if separated by weeks or months

• Inflammation in early life accelerates the cellular and molecular aging of HSCs

• Mice exposed to inflammation develop features of aged human hematopoiesis

Research Paper:

1-s2.0-S1934590922002612-main.pdf (3.9 MB)

Related:

Interesting twitter thread on this new paper by one of the authors:

Record for longest twitter thread.

Very cool study, I’ve always had this intuitive sense that someone experiencing significant inflammation in younger years, it would deliver a step change downward to their health over time.

My mom had some chronic pain condition in mid life (lasted a long time)…she has AD (pure speculation of course, she had some other risk factors, just n=1)

“In this study, we perform a painstaking time course analysis spanning periods of up to 1 year after cessation of inflammatory challenge, in order to unequivocally demonstrate that there is no subsequent regeneration of the HSC pool and that activation of HSCs out of dormancy is not a fully reversible process, as previously thought”

What is 1 yr in mouse life to human…25 yrs? At least a very significant time span.

Definitely going to add IL-6/TNalpha next panel…just to give better insight systemic inflammation.

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This makes you wonder about the implications of repeated Covid infections. I know some patients who’ve had it 3 times already. What is the damage to their HSC’s from repeated infections/ inflammation ?

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Indeed, repeated cytokine storms!!

I think there have been some studies now on long covid…do you know if inflammation is major systemic marker?

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Various cytokines measured prior to Covid hospitalizations offer very good prognostic information.

Even a high triglycerides/ HDL is a poor prognosis due to its inflammatory implications.

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"The researchers found that pro-inflammatory cytokines and chemokines, such as IFN-γ, IL6, TNF-α, and CCL-11, were substantially elevated compared to healthy controls both in blood serum and in cerebrospinal fluid (CSF) seven days after infection. Most notably, CSF levels of CCL-11, a chemokine associated with age-related cognitive impairment [3], continued to increase. After seven weeks, CCL-11 was much higher than it was seven days after infection.

Just as the researchers suspected, microglia reactivity in subcortical white matter, but not in cortical grey matter, was also elevated seven days after infection and persisted at least until the end of the follow-up periodIn line with previous research showing that microglial overactivation can inhibit neurogenesis [4], the researchers detected a stark decrease in the production of new neurons in the hippocampus, which was inversely correlated with the actual load of reactive microglia.

Conclusion

This study shows that even mild infection with SARS-CoV-2 can lead to a long-term increase in neuroinflammation, which correlates with the experience of “brain fog” in long COVID. While it is possible that neuroinflammation levels go back to normal in the long run, its consequences might linger. COVID probably still holds some unpleasant surprises and should be avoided at all reasonable costs."

Well, today I went down my daily favorite rabbit hole Google Scholar. I almost hate to go there because one thing leads to another and now I am looking into the possibility of supplementing with methylene blue. Many articles indicate it may help with Covid and other viral infections such as Zika.:

Covid Treatment

The only drug known to inhibit the excessive production of reactive species and cytokines is methylene blue,

“biochemical properties of methylene blue that was called once upon a time a “magic bullet” for healing a wide range of diseases.”

We report the case of a cohort of 2500 French patients treated among others with methylene blue for cancer care. During the COVID-19 epidemics none of them developed influenza-like illness. Albeit this lack of infection might be by chance alone, it is possible that methylene blue might have a preventive effect for COVID-19 infection. This is in line with the antiviral activity of Chloroquine, a Methylene blue derivative. Both Chloroquine and Methylene blue have strong antiviral and anti- inflammatory properties probably linked to the change in intracellular pH and redox state.

https://riviste.fupress.net/index.php/subs/article/view/888/548

retinal photoreceptor degeneration

The absolute bioavailability of MB is high.

Protective effect of methylene blue on TNBS-induced colitis in rats mediated through the modulation of inflammatory and apoptotic signalling pathways

“Methylene blue used as an adjunctive medication improved residual symptoms of depression and anxiety in patients with bipolar disorder.”

from

to

Zika virus

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image

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Well, it may be hard being blue. :smiling_face_with_tear:
Wait, my friend just told me: “You can be blue or you can be sick.”
BTW, do you ever sleep?

Sleep 11-7 rigid protocol

Tried it for a while. No side effects. Didn’t notice much so now it’s sitting on my desk . Need to get a pharmaceutical quality.

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Yeah, it’s nasty.

Problem is that the vaccines don’t prevent getting infected, just the severity.
I have this very effective and highly breathable mask made by airgami.

Response from Paper author on my question:

What kind did you buy powder or liquid, and what was the reason to try methylene blue.
How did you take it?

I was not interested or knew about its anti-viral properties, so I won’t address that.

It is widely touted as a brain enhancer, I really didn’t know anything about it other than its use as dye. I had no idea folks were actually ingesting it.

My main goal at this point is to preserve my brain. Physically I feel top-notch at this point. I have more than adequate muscles for my needs and I believe rapamycin and exercise will delay any loss for a long time.

My brain does not feel as fit as my body and anything I can do to improve brain function, other than exercise which I already do is my current goal.

“Consistently, MB is one of the most effective agents to delay senescence in normal human cells”

Its role in the mitochondria, however, has elicited much of its renewed interest in recent years. MB can reroute electrons in the mitochondrial electron transfer chain directly from NADH to cytochrome c, increasing the activity of complex IV and effectively promoting mitochondrial activity while mitigating oxidative stress. In addition to its beneficial effect on mitochondrial protection, MB is also known to have robust effects in mitigating neuroinflammation
https://link.springer.com/article/10.1007/s12035-017-0712-2on.

Methylene blue (MB) is a well-established drug with a long history of use, owing to its diverse range of use and its minimal side effect profile

“Together the findings suggest that low-dose MB enhances spatial memory retention in normal rats by increasing brain cytochrome c oxidase activity”.

Currently, MB has been shown to attenuate the formations of amyloid plaques and neurofibrillary tangles and to partially repair impairments in mitochondrial function and cellular metabolism.

“potential treatment of neurodegenerative disorders such as Alzheimer’s disease (AD), possibly through its inhibition of the aggregation of tau protein.”

I took it for its role in mitochondrial function and it’s apparently very safe. I got it in liquid form from bluebrainboost. I think I took 10 mg per day.

Thanks!
Not joking, did anything other than your urine turn blue? For instance the whites of your eyes, any change in skin color.
Also, how did you take it, to prevent your mouth and tongue from turning blue?
As for efficacy, my motto is, “you can’t fix it if it’s not broken”.
For instance, I am sure most young users of rapamycin will feel no subjective effect. Whereas an old folk like me really feel some benefits.

I put everything into coffee. My coffee isn’t even coffee anymore.
Nothing turned blue but you have to be careful handling it because it’s a potent strainer.

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No, not into my coffee! My straight black coffee is sacred to me.
I have experimented with putting trehalose, etc into it and I just not going to do it anymore. I put all of my stuff like hawthorn berry trehalose etc into or on top of my oatmeal or mix it with my protein shake.

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Oatmeal would be a good choice. Why hawthorn berry?