NLRP3 Inflammasome Cause Of Male Pattern Baldness

[MitchMitchell]

like to imagine that if the Ray Peat / pro metabolic community can legitimately surpass the mainstream big 3 'treatments' - itd lead to a huge awakening in the masses view of mainstream pharmaceuticals/thyroid/scientism

It’s good to be optimistic but no, that won’t happen. Get testosterone t3 Dhea progesterone up and carry on. Insulin and HBA1c both around 5

 

[GorillaHead]

It’s good to be optimistic but no, that won’t happen. Get testosterone t3 Dhea progesterone up and carry on. Insulin and HBA1c both around 5

i dont understand why progesterone is suggested. My understanding is it puts potassium in the cell.

By way of minoxidil which is a potassium channel opener. Releasing potassium from the cell. This would mean we dont want progesterone it counters cortisol. Have any of you guys looked up patients with cushings. Men more often seem to show juvenile hairlines. While women seem to show thinning.

 

[LeeLemonoil]

Insulin resistance where GC is dsyfunctional and Androgens act as GC surrogates might be useful to prevent the fibrotic, quasi-senescent cells into cancer cells. Senescent cells use up energy very rapidly. As I guessed earlier in this thread, Androgens substituting for GCs might be a way to prolong life, or better, prevent more direct, imminent death by Cortisol directly wreckng tissue (or causing malign fast growing cancer) - I don't know if this is canonical knowledge. I just made that up and to lazy to research if there is soemthing known about it already

 

[LeeLemonoil]

By way of minoxidil which is a potassium channel opener. Releasing potassium from the cell. This would mean we dont want progesterone it counters cortisol. Have any of you guys looked up patients with cushings. Men more often seem to show juvenile hairlines. While women seem to show thinning.

Interesting, Would corrobate the OP's theory.

 

[GorillaHead]

Any of you all interested in getting on a zoom or blue jeans call where we can bounce ideas and hammer this out.

i swear if i was a professor i would launch Hairloss class. Id probably solve this with thousands of student minds

 

[Inaut]

This is my favourite thread on the forum right now. Good work everyone and thanks to OP for starting this off!

 

[LeeLemonoil]

Any of you all interested in getting on a zoom or blue jeans call where we can bounce ideas and hammer this out.

i swear if i was a professor i would launch Hairloss class. Id probably solve this with thousands of student minds

Why not. Different time zones might be a problem. Maybe some weekend after new year?
I'm not a hairloss-guy though, never looked much into the various threads. But NLP3 is intersting. Regardlees, any condition where pathomechanisms can be eludicated is worthwhile

 

[LeeLemonoil]

Striking Accumulation Of PUFA In Aged Cells

Striking Accumulation Of PUFA In Aged Cells

Peat has written many times about the changes that occur in "aged" cells. Those changes are virtually indistinguishable from the ones that occur in "sick" cells and are characterized by reduced mitochondrial number/size and a shift in lipid composition away from saturated and towards unsaturated fats. The crucial mitochondrial lipid enzyme cardiolipin (CL) comprises at least 20% of the lipids present in the inner mitochondrial membrane and its lipid composition determines it ability to both stabilize the inner mitochondrial membrane and proton flow across it as well as carry electrons between Complex III and Complex IV in the electron transport chain, and ensure proper structure of Complexes III, IV and even V. The more unsaturated the lipid composition of CL is the more vulnerable to attack/destruction by those electrons it carries is, and thus the more vulnerable Complexes III, IV, and V that contain CL are as well. In other words, more PUFA in the cell = more structural disintegration and less OXPHOS.

Thus, one would expect that aging (and disease) to be associated with a shift in cellular lipid composition in general (and CL composition in particular) towards PUFA. However, up until now evidence for age-related changes in cell lipid composition in favor of PUFA has been sparse to non-existent. The study below changes the status quo by demonstrating that senescence is characterized by a striking accumulation of PUFA inside cells. In fact, of the 19 types of triacylglycerols present in relative abundance in aged cells compared to adult ones, every single one of those glycerol types contained at least one PUFA member. The study does not go as far as to say that this accumulation is what drives aging because the study only looked at association, not causality. However, the fact that the level of PUFA accumulation was age-dependent implies causality and the knowledge about the effects of PUFA on CL function seals the deal, at least for me. The conclusion of the study was that lipids are far from passive when it comes to health and aging and they may regulate the very process of aging itself. I will go a step further and state that PUFA accumulation is the major cause of cell aging and reversing that accumulation likely restores a cell's biological age back to youthfulness.

Regulation of lipids is central to replicative senescence - Molecular BioSystems (RSC Publishing)

"...Cellular replicative senescence, a state of permanent cell-cycle arrest, has been linked to organismal aging, tissue repair and tumorigenesis. In this study, we comparatively investigated the global lipid profiles and mRNA content of proliferating and senescent-state BJ fibroblasts. We found that both expression levels of lipid-regulating genes and the abundance of specific lipid families, are actively regulated. We further found that 19 specific polyunsaturated triacylglycerol species constituted the most prominent changes in lipid composition during replicative senescence. Based on the transcriptome analysis, we propose that the activation of CD36-mediated fatty acid uptake and diversion to glycerolipid biosynthesis could be responsible for the accumulation of triacylglycerols during replicative senescence."

As cells age, the fat content within them shifts - University at Buffalo

"...As cells age and stop dividing, their fat content changes, along with the way they produce and break down fat and other molecules classified as lipids, according to a new University at Buffalo study. “Traditionally, lipids have been thought of as structural components: They store energy and form the membranes of cells,” says G. Ekin Atilla-Gokcumen, PhD, an assistant professor of chemistry in UB’s College of Arts and Sciences. “Our results add to evidence that lipids may actually play a much more active role in the body, in this case, in the process of replicative senescence, which is linked to cellular aging. This is a new, emerging field of study.”

"...When the researchers compared the lipid content of young cells to older cells, some interesting trends emerged. In senescent cells, 19 different triacylglycerols, a specific type of lipid, accumulated in substantial amounts. These increases occurred in both lung and foreskin fibroblasts, showing that such changes are not limited to a single variety of cell."

"...The study found that during cellular senescence, the accumulation of triacylglycerols corresponded with a significant increase in the levels of genes involved in responding to oxidative stress...All had a remarkably similar structure, featuring long chains of fatty acids, including at least one polyunsaturated fatty acyl (PUFA) chain."

 

[GorillaHead]

So sirt2 will lower nfrp3 and low glucose conditions activate sirt2.

again this is all about fat and insulin resistance. but its a localized problem.

The scalp has a high level of subaceous glands. Its exposed to high levels of fat. Long term aga leads to the follicle being replaced by fibrosis and fat.

also
The Relation of Androgenetic Alopecia Severity with Epicardial Fat Thickness

 

[GorillaHead]

Also cortisol thins the skin. While dht thickens it.

they most def counter each other

 

[GenericName86]

Also cortisol thins the skin. While dht thickens it.

they most def counter each other

Could be why people who are under chronic stess sometimes report thinner skin, like the say they bruise easier etc.

 

[Tristan Loscha]

Influence of the salt intake on the loss of scalp hair
10.1111/j.0954-6820.1957.tb00117.x

 

[GorillaHead]

Could be why people who are under chronic stess sometimes report thinner skin, like the say they bruise easier etc.

Definitely.

Influence of the salt intake on the loss of scalp hair
10.1111/j.0954-6820.1957.tb00117.x

View attachment 20519

so answer potassium?

 

[Tristan Loscha]

Alopecia and associated toxic agents: a systematic review
Vicky Yu, Margit Juhász, Audris Chiang, Natasha Atanaskova Mesinkovska
Skin Appendage Disorders 4 (4), 245-260, 2018
Importance/Objective: There are a number of toxic agents that can cause alopecia. In this review we summarize the known substances that cause alopecia as one of the clinical signs of overdose or toxicity. Evidence Review: A search was conducted using PubMed, EMBASE, and Cochrane for studies describing hair loss of any type as a result of exposure to or ingestion of a toxic agent. The search yielded 856 articles, with 47 studies included in this review. Findings: Agents with the strongest evidence of association to alopecia include thallium, mercury, selenium, and colchicine. Agents with described incidents include boric acid, arsenic, vitamin A, botulinum toxin, Podostroma cornu-damae, and the synthetic opioid MT-45. Conclusions and Relevance: Numerous toxic agents have been implicated in alopecia, and the strength of evidence behind each agent varies. Toxic levels of thallium and colchicine have long been established to cause alopecia, as compared to agents such as botulinum toxin A and synthetic recreational drugs which have less literature describing their links to alopecia and will need further investigation to characterize their relationships to hair loss. Knowledge of typical presentations of hair loss will aid in the development of a differential diagnosis for patients presenting with alopecia.




Also mildly interesting interventions in male pattern baldness:
https://www.karger.com/Article/PDF/492035

 

[Tristan Loscha]

Definitely.


so answer potassium?

Theophylline was mentioned in the Foldes anecdote, potassium increases natriuresis and chloruresis and is important, and caffeine shampoo seems to be ok also, see the study i attached one reply earlier. I feel that NaCl has signalling activity that can be independent of balance relationships, and has total either/or signalling, which, if true, could only be overridden by reduction/normalization at the level of intake.

 

[LeeLemonoil]

Also cortisol thins the skin. While dht thickens it.

they most def counter each other

But dht might achieve thickening by way of fibrosis or hyperplasia. Not deadly, but not optimal

 

[GorillaHead]

Involvement of NLRP3 inflammasome in the impacts of sodium and potassium on insulin resistance in normotensive Asians - PubMed

 

[LeeLemonoil]

Let’s come up with integrative theory on hairloss or nlrp3 action in general with all angles covered and give it to Peat for proof-reading

 

[PhilParma]

Influence of the salt intake on the loss of scalp hair
10.1111/j.0954-6820.1957.tb00117.x

View attachment 20519

I style my hair with salt water. Bad idea?

 

[JDreamer]

So sirt2 will lower nfrp3 and low glucose conditions activate sirt2.

again this is all about fat and insulin resistance. but its a localized problem.

The scalp has a high level of subaceous glands. Its exposed to high levels of fat. Long term aga leads to the follicle being replaced by fibrosis and fat.

also
The Relation of Androgenetic Alopecia Severity with Epicardial Fat Thickness

Replaced by fibrosis and fat? Studies posted on this forum have shown brown fat is considerably less in autopsies of balding/bald scalps.