Stimulation Of Hair Growth By Small Molecules That Activate Autophagy

[fugged]

Dont know if anyones seen this, but its interesting. Yes, another mouse study, but autophagy is getting lots of discussion with regard to overall health, keeping your telomeres from shortening, and the like. Stimulated by heat and cold shock, fasting, and excercise to name a few. Im still digesting it but it seems this molecule, α-ketoglutarate is available, and dramatically induced anlagen in the study... Like to hear others thoughts, could this be a new topical?

https://www.sciencedirect.com/science/article/pii/S2211124719306990

 

[fugged]

seems like someone has already applied for a patent for this and some others molecules as a topical:
https://patents.google.com/patent/WO2018064468A1/en

 

[fugged]

Its also good for collagen production, used here for anti wrinkles:
https://www.ncbi.nlm.nih.gov/pubmed/17666792

 

[Armando Jose]

What I do not explain is how they give a patent in 2016 when at least in 2007 (study) it was already public. Is it really new?

BTW Autophagy keep your telomeres from shortening? It is strange?

 

[fugged]

You aren't making any sense with that comment/question.

The patents for hair loss were in play around 2016-2018.
The wrinkle study from 2007 just demonstrates it induces collagen.
The patents were for hair loss, not wrinkles or collagen, nothing to do with each other.

The new study from June 2019 discusses α-ketoglutarate and hair growth.

 

[Armando Jose]

You are right

 

[fugged]

BUMP

 

[ScentlessApprentice]

Topical Metformin and topical Rapamycin could be obtained too. Metformin has been around for ages and has a good safety record. It's currently being studied for longevity.

I too have been reading up on autophagy recently and have begun doing the 16:8 intermittent fasting which supposedly promotes it. How does autophagy work for skin? Does fasting induce it, or do we need a cream? The word itself seems to be just a catch all.

 

[fugged]

why is no one interested in these molecules and what they may do!? Ill post it for you

Molecules that can promote hair follicle stem cell activation and anagen initiation have been intensely searched for, as they may both help reveal how hair regeneration is regulated and provide therapeutic and cosmetic interventions. Here, we postulate that telogen hair follicles may be induced to enter anagen by pharmacologically triggering autophagy.

The unforeseen finding that supplementation of a metabolite α-ketobutyrate (α-KB) in old mice can increase longevity and prevent alopecia (Huang et al., 2016) suggests that rejuvenating aging or aging associated deficiencies may restore hair follicle stem cell function and hair growth in skin.

Here we tested whether α-KG can increase hair regeneration, using a commonly used in vivo C57BL/6J mouse dorsal skin model. We mainly tested the topical treatment method, as it is most easily translated to human patients.

α-KG treatment drastically enhances hair regeneration (Figures 1A and 1B).

Hair grew from the pigmented skin area of α-KG-treated mice within 5–7 days, and by day 39 post-treatment, α-KG-treated mice exhibited robust hair growth; in contrast, control mice showed little or no hair growth overall (Figure 1B). The effects of α-KG on anagen initiation and hair regeneration were even more dramatic when mice were treated later in telogen at 8 weeks of age (Figures S1B and S1C). α-KG stimulation of hair growth is gender independent; α-KG exhibited similar hair stimulating effects in female mice (Figure S1D).

Disrupted autophagy has been linked to neurodegenerative diseases, cancer, and other age-related disorders. Given the conservation in energy metabolism and autophagy machinery, induction of hair regeneration by autophagy activation discovered in mice herein should translate to humans. Although it has not been tested in human hair regeneration studies, autophagy has been shown to be essential to maintaining the growth of an ex vivo human scalp hair follicle organ culture (Parodi et al., 2018).

Although our study did not use a model for alopecia, the findings are relevant to hair loss in the following way. First, hair regeneration, which occurs cyclically under normal conditions but fails in alopecia, would require reactivation of dormant hair follicle stem cells.

 

[fugged]

Topical Metformin and topical Rapamycin could be obtained too. Metformin has been around for ages and has a good safety record. It's currently being studied for longevity.

I too have been reading up on autophagy recently and have begun doing the 16:8 intermittent fasting which supposedly promotes it. How does autophagy work for skin? Does fasting induce it, or do we need a cream? The word itself seems to be just a catch all.

Fasting induces it, but how that relates to the stem cells in follicles I don't know. This study was mainly on topical application.

 

[fugged]

BUMP

 

[ScentlessApprentice]

https://www.simplesanutrition.com/products/akg-liquid-4-oz.html

This what we need?

 

[Capone]

Fasting induces it, but how that relates to the stem cells in follicles I don't know. This study was mainly on topical application.

You ever see the state of people on calorie restrictive diets? They look horrendous. Frail and weather beaten.

 

[fugged]

Right, like this guy.

 

[fugged]

I dont know, that has flavor and a few other ingredients. Not sure we need the lemon flavor in our hair. I bought a capsule from from Klaire labs (also has some other ingredients). We really dont know at this point. It mixes with water and stores reasonably well apparently.

 

[Otis Mack]

Topical Metformin and topical Rapamycin could be obtained too. Metformin has been around for ages and has a good safety record. It's currently being studied for longevity.

I too have been reading up on autophagy recently and have begun doing the 16:8 intermittent fasting which supposedly promotes it. How does autophagy work for skin? Does fasting induce it, or do we need a cream? The word itself seems to be just a catch all.

CHRONIC metformin treatment will ___cause___ hair loss according to many who take the drug orally for Type2 diabetes. Not all...but many.

Acute metformin treatment will cause autophagy but chronic usage will damage the mitochondria resulting in the hair loss.


Some points:

1) some molecules only cause autophagy in vitro when bathed in the substance for 24 hours and have zero effect in vivo. Trehalose would be
an example of that.

2) autophagy effectiveness is hindered by lipofuscin. These studies tho are on post-mitotic cells and I dont know if that applies to mitotic cells.
My guess is that lipofuscin does still build up over time even in mitotic cells otherwise there wouldn't such a thing called "liver spots" in skin cells.
If lipofuscin is a problem then cylclodextrin would rapidly dissolve it which it is hard to find chemicals that do without toxicity.

https://www.fightaging.org/archives...ble-treatment-for-the-build-up-of-lipofuscin/

3) stacking almost always across the board results in better response. Cocktails are no secret to the medical community...
Pubmed paper recommends hitting various pathways.

4) alpha KG supplementation anecdotes seem to suggest it causes hair loss. Altho I don't know why for sure, the hair follicles dont like one form of butyrate and this might include alpha KG also.

Ketones that we have in our metabolism are: acetone and butyrate.

https://www.ncbi.nlm.nih.gov/pubmed/2045676

Most of the anecdotes I remember weren't used for hair growth in Androgenetic Alopecia but for weight loss. If we are somehow starving the hair follicle of glucose(say by reduced microcirculation) then it would be advantageous to use alpha KG(read above study) and might be an interesting topical

re:microcirculation and insulin resistance( https://www.sciencedirect.com/science/article/pii/B9780128000939000235)


5) I'm not sure we really want "always on" autophagy either. Normally levels of autophagic indicators are low. Autophagy is HIGH in many diseases.

6) read longecity alot... check out Turnbuckle's comments on various things. He suggests that autophagy is rather stressful to a cell.
Check out his thread: https://www.longecity.org/forum/topic/94224-manipulating-mitochondrial-dynamics/

 

[fugged]

Intermittent fasting and the autophagy it induces is by all accounts good for general health, as it clears senescent cells which cause disproportionate aging and damage, check Rhonda Patricks work on this. What I am referencing here is that the topical, especially alpha ketoglutarate induced autophagy in hair cells and stimulated new growth (in mice), nothing about taking metformin, which is hard to get anyway. As and aside, look at David Sinclair of Harvards hair, he takes a gram a day for longevity. His biological age is well below his calendar age, and just look at him.

I think autophagy is stressful to cells, that's the point... The senescent and precancerous cells can't hang with the stress so they die, the body cannabilizes them and when you refeed, the body rebuilds only the healthy cells. Ive only applied this aKG once.. Either way, I dont think fasting will necessarily help anyones hair per say, but it will help you overall. Its the triggering of hair follicles out of quiescence that got me interested in alpha KG by applying it topically. But I dont have any idea of the intricacy of it all, just throwing the paper up for discussion and thought.