NLRP3 Inflammasome Cause Of Male Pattern Baldness

[LeeLemonoil]

EDIT: I see now. His foundation of anti aging can be summed up in this quote. He wants stress. But not to the point of excess distress. I think there's definitely something to be said about it" "...“Longevity is correlated with having and meeting a healthy level of challenge – not too little and not too much stress.” A later 2009 blog entry Hormesis and age retardation started out by saying “An important approach to retarding aging that I have not discussed explicitly so far is hormesis, challenging cells and body systems by mild stress resulting in them becoming stronger and resistant to aging(ref). The stress can be physical, chemical and even possibly psychological.”"

This true. And the RPF is not the best place to discuss hormesis since Peat is not too fond of the concept.
There is a lot of material available about autophagy, it’s role in aging/anti-aging and why and how it evolved and functions.
It’s the one point that I personally cannot square well with Peats focus on keeping a super energy metabolism. According to conventional knowledge, that would cause faster aging and disease - we have had many topics here why that also is not entirely true. But if we figure that out we are in for the novel prize 10 years in a row.

Anyway it seems more promising to use the autophagy mimicry by some substances to help the scalp on cellular level. Not amount of fasting or excervisd will bring back hair

 

[LeeLemonoil]

Then they documented the effects of glucocorticoid receptor (GR) stimulation on AR expression and activity. They demonstrate that the GR and corticosteroids positively regulate AR expression while simultaneously decreasing AR activity and altering androgen effects on adipogenesis. The impact of dihydrotestosterone (DHT) on androgen receptor conformation during adipogenesis is also investigated. These findings are supported by high content analysis and quantitative imaging assays that were used previously by this group to investigate estrogen receptor ligands (Ashcroft et al., 2011).”

Wow, that one needs to be studied diligently and understood and reconciled with the hypothesis. This will give key understanding of the downstream part of the pathomechanism, how effect GC sensitivity would influence AR expression and the effects of dht on them.

Another nice crossconnection.
Tagged on this thread are two more threads. One showing that good dopamine signaling inhibits nlrp3.
That’s so fundamentally logical.

And one shows omega3s inhibiting the mechanisms. We love to hate or hate to love Omega3. Another paradox. Anti-inflammatory but also pro aging, pufaesque.
It seems it is in the estrogen category. It helps acutely and sepecificald but you wouldn’t want that as the primary aid

 

[334c]

A couple more articles possibly related:

(this could help interpet the male phenotype of )
- prostate cancer risk
- baldness risk
- cardiovascular health issues

in both cases its some kind of inflammation

finasteride functions (aside from slowly destroying the organism), inhibits the androgens from a nasty inflammatory cycle - women related to this phenotype (or was it genotype idk i never payed attention in bio class lol), simply avoid AGA and related inflammation due to their lack of androgens and estrogens autohpagy affect.


The Role of microRNA-221 and microRNA-222 in Androgen-Independent Prostate Cancer Cell Lines
The Role of microRNA-221 and microRNA-222 in Androgen-Independent Prostate Cancer Cell Lines


The role of mitochondria in NLRP3 inflammasome activation
The role of mitochondria in NLRP3 inflammasome activation - PubMed

i'm not really good at deeply interpreting these articles, however these are my thoughts:

we understand protein-wise what exactly is the leading to the vicious cycle of androgen induced chronic inflammation and fibrosis

and what difference is occurring in the men who maintain a full head of hair into old age.

--

once this bioenergetic community can figure out a balance of ideal / hyperthyroid state i.e. glucose nourishment (no ffa damage) and also how to use autophagy we could probably achieve immortality and reverse ageing.

daily bathing in caffeine perhaps?

 

[LeeLemonoil]

I Just checkd a but of nlrp3 and my corneal-illness speciality. Not much is known but one study from this year shows nlrp3 inflammasoe as one cause of keratocyte getting into inflammatory mode.

The condition I write about, called Keratoconus is just on its way to get decrypted fundamentally, biochemically.
All id still obscure but lots of thinks like LOX, energy metabolism and prolactin is involved. Nobody would have thought about hormonal stuff there not many years ago.

I don’t know if nlrp3 (or other nlrp-inflammasomes) are the main culprit for everything but it seems very very high upstream.

The question is why is there a mechanism that would be so detrimental? What does it achieve when it’s functional and not overactive?

 

[334c]

One showing that good dopamine signaling inhibits nlrp3.

this makes me consider how a persons psychology and their beliefs may directly influence their health and inflammation.

not to go full crank, but its vital to have an open mind:

makes me think of this thread:
These Dudes Claim They Cured MS And All Kind Of Diseases

BioLogos - God's Word. God's World.

ive yet to fully read up on the bios logos thing, it ma be a cult or a scam for all ik lol.

 

[334c]

Dopamine controls systemic inflammation through inhibition of NLRP3 inflammasome
Dopamine controls systemic inflammation through inhibition of NLRP3 inflammasome - PubMed

 

[LeeLemonoil]

Dopamine controls systemic inflammation through inhibition of NLRP3 inflammasome
Dopamine controls systemic inflammation through inhibition of NLRP3 inflammasome - PubMed

Nice one.
Intricate stuff. Dopamine itself being interconnected with androgen Situation and energy metabolism. Hard to say what is egg and what hen.

And certainly people with positive mindsets have willed down illnesses. The question is if that mindset is achievable by everyone. Something in their physiology enabled them to have a good mindset -> good dopa -> low inflammation. They had the luck to have that luck so to say.

In any case, another hint that nlrp3 is in the midst of many pathologies. I’d say that inhibiting that one would have good effects on dopamine tone and Situation too just ad vice versa is proven.

Peat described early the basic dualism of dopamine - anti-inflammatory and serotonin pro.

 

[Inaut]

Molecular hydrogen inhibits lipopolysaccharide-triggered NLRP3 inflammasome activation in macrophages by targeting the mitochondrial reactive oxygen species


Molecular hydrogen inhibits lipopolysaccharide-triggered NLRP3 inflammasome activation in macrophages by targeting the mitochondrial reactive oxygen species - ScienceDirect

 

[LeeLemonoil]

Dopamine Receptor Subtypes Differentially Regulate Autophagy

 

[LeeLemonoil]

In other illnesses nlrp3 causes altered lipid metabolism and genetic changes via that.

It seems that autophagy needs to be in balance too for the desired effects. Taurine might be a substance to balance that.

Note that nlrp3 modulation here alone wasn’t enough to prevent the Lipid chabges in the tissue. That might play a role in hairloss too that would need to be Adressed. The Lipid changes might induce long lasting genetic changes responsible for mpb and treatment resistance

Taurine attenuates arsenic-induced pyroptosis and nonalcoholic steatohepatitis by inhibiting the autophagic-inflammasomal pathway

 

[LeeLemonoil]

The Thread title is misleading I now realize. according to the their here nlrp3 is Part of the mechanism but not the actual cause why cells stop producing hair as desired. In the end there have to be transcription changes in genes probably.

Autophagy: there has to be a fine tuned homeostasis at „how much“ autophagy prevents nlrp3, especially when we assume that xenobiotics like mould are at play.
Autophagy would destroy those invaders, leaving particles behind that do not activate nlrp3.
Would there be a too much of that? And when would autophagy Digest itself structures unwanted. It is freakishly complex as always

 

[334c]

c

The Thread title is misleading I now realize. according to the their here nlrp3 is Part of the mechanism but not the actual cause why cells stop producing hair as desired. In the end there have to be transcription changes in genes probably.

Autophagy: there has to be a fine tuned homeostasis at „how much“ autophagy prevents nlrp3, especially when we assume that xenobiotics like mould are at play.
Autophagy would destroy those invaders, leaving particles behind that do not activate nlrp3.
Would there be a too much of that? And when would autophagy Digest itself structures unwanted. It is freakishly complex as always

would caffeine simply regulate the ideal amount of autophagy?
i heard caffeine promotes the intake of progesterone and thyroid - would this work to nourish the cells / promote growth?

i wonder if topical caffeine and taurine could simply keep everything in check

 

[LeeLemonoil]

Possibly but getting stuff into the cells is always the caveat. Along with micro needling maybe which itself has effects on the pathways
Just like there are anecdotes about isotretinoin and needling lead to regrowth

 

[Kvothe]

i wonder it somehow its possible to produce the desirable autophagy that new agers / mainstream people promote as the secret to youth etc with out the destructive metabolic effects that Ray describes in this video

Of course it is. Low-protein diets increase autophagy, insulin sensitivity, longevity, etc. because an excess of certain amino acids stimulates the activation of the mTor pathway. and the suppression of controlled autophagy. You can basically get all of the benefits of fasting without restricting calories, at all.

 

[334c]

Im trying to make sense of the comment guys explanation:


There is stress and inflammation

Nlrp3 detects the inflammation

Casp1 shows up as part of the inflammation reaction

Unfortunately Casp1 cleaves the glucocorticoid receptors

This induces glucocorticoid resistance / the glucocorticoids were supposed to fulfil the stress response, but they don’t

And so the inflammation persists

then androgens show up to assist in reducing the inflammation

However the androgens prevent autophagy (which would have been necessary for ending the inflammation and allowing hair growth)

and further perpetuate the Nlrp3 inflammation


Androgen aggravates liver fibrosis by activation of NLRP3 inflammasome in CCl 4-induced liver injury mouse model
https://pubmed.ncbi.nlm.nih.gov/32182125/


Supraphysiological Levels of Testosterone Induce Vascular Dysfunction via Activation of the NLRP3 Inflammasome
Supraphysiological Levels of Testosterone Induce Vascular Dysfunction via Activation of the NLRP3 Inflammasome


i think the genetic ‘factor’ may be that some people create more Casp1 and more nlrp3 leading glucocorticoid receptor residence. which i think is suggested in the quote below:



“Our genome-wide analysis of DNA methylation revealed a highly significant relationship between lower levels of CASP1 promoter methylation and elevated CASP1 mRNA expression, and, concordantly, a highly significant relationship between lower levels of NLRP3 promoter methylation and higher NLRP3 mRNA expression in glucocorticoid-resistant ALL cells compared to glucocorticoid-sensitive ALL cells. Based on a published report of CASP1-mediated androgen receptor5 cleavage, we used bioinformatics to identify 2 similar CASP1 cleavage 4-residue motifs (LLID and IKQE) in the transactivation domain of the glucocorticoid receptor and experimentally confirmed their clinical relevance (Fig. 1). When overexpressed and activated in human leukemia cells lines, CASP1 increased glucocorticoid resistance by cleaving and inactivating the receptor, preferably at the LLID site; this could be mitigated by either downregulation of CASP1 expression or by overexpression of the cowpox virus protein CrmA, a known inhibitor of CASP1.6

Inflammasome-mediated glucocorticoid resistance: The receptor rheostat
Inflammasome-mediated glucocorticoid resistance: The receptor rheostat



i think that some genotypes over-express Casp1 and thus (speculating here) before the glucocorticoids can adequately fulfil their function, the excessive Casp1 cleaves the receptors?

And so the inflammation is unregulated / perpetuated


In others with full heads of hair the inflammation ends as the GCs are used up and thus adequate glucose oxygen function returns after the stressful event is resolved

The presence of inflammation along with unused glucocorticoids starve the hair follicle of glucose metabolism?

In other words they waste resources / sugar / aminos etc because the stress response of inflammation cannot complete / be concluded


i wonder if the resisted glucocorticoids go on to waste the sugar / oxygen / amino acids and lead the ‘hypothyroid’ state cascade as described by Danny here:
The Danny Roddy Weblog


So it may not merely be hypothyroidism, but a genetic predisposition to glucocorticoid resistance

And when Danny roddys that he thinks that some people inherit the “fragility” in other words stress physiology this is more accurately what he would be referring to.



I have some more interesting things to write about regarding glucocorticoid resistance

 

[334c]

Of course it is. Low-protein diets increase autophagy, insulin sensitivity, longevity, etc. because an excess of certain amino acids stimulates the activation of the mTor pathway. and the suppression of controlled autophagy. You can basically get all of the benefits of fasting without restricting calories, at all.

ahh so fruit fasting?

 

[Ndrake]

https://www.researchgate.net/publication/341537629_Selenium_Plays_an_Anti-Inflammination_Role_by_Regulation_NLRP3_Inflammasome_in_Staphylococcus_aureus-Infected_Mouse_Mammary_Gland

Selenium Plays an Anti-Inflammatory Role by Regulation NLRP3 Inflammasome in Staphylococcus aureus-Infected Mouse Mammary Gland

The result showed that compared with the control group, selenium significantly inhibited the expression of NLRP3, ASC, Caspase-1, Caspase-1 p20, and Pro-IL-1β

 

[Inaut]

Not to keep bumpinng hydrogen water but it mimics fasting without having to fast. I’ve also read accounts of it being applied to the hair for colour restoration and hair loss.

 

[Zigzag]

Possibly but getting stuff into the cells is always the caveat. Along with micro needling maybe which itself has effects on the pathways
Just like there are anecdotes about isotretinoin and needling lead to regrowth

This is weird, because as far as I know isotretinoin is terrible for hair.

 

[334c]

im learning about Chrousos syndrome - which is like a mild cushings, due to glutocorticoid resistance, im not sure if its true but i wonder if all people with AGA are a mild to moderate manifestation Chrousous syndrome.

if anyone here could help me figure out:

its the normal function of Casp1 in all humans to cleave the glutocorticoid receptor or is this a genetic thing?

if casp1 naturally cleaves the GC receptor it would imply the glutocorticoid resistance is due to an excess of Casp1 and nlrp3 production (due to a mutation / adaptation / genetic expression) (excess as the casp1 is too present and too readily cleaves)

or
is it the case that in some people either the glucocorticoid receptor has mutated, or the Casp1 has mutated?

from which glucocorticoid resistance occurs.

knowing this would help a tremendous amount