Activating Hair Follicle Stem Cells to Enhance Hair Growth

This work, I think, is not significant for the hair growth, but for the fact that the researchers involved have found a simple way to enhance the activity of a stem cell population. It suggests that the research community might expect to find analogous (but probably quite different) simple ways to selectively achieve the same outcome in other stem cell populations that support other tissue types. Losing hair is somewhere in the vicinity of inconvenient and annoying. There are any number of other tissues in which the age-related decline of stem cell activity is ultimately fatal, and those seem to me to be the more important challenges to focus upon.

Hair follicle stem cells are long-lived cells in the hair follicle; they are present in the skin and produce hair throughout a person's lifetime. They are quiescent, meaning they are normally inactive, but they quickly activate during a new hair cycle, which is when new hair growth occurs. The quiescence of hair follicle stem cells is regulated by many factors. In certain cases they fail to activate, which is what causes hair loss.

Researchers found that hair follicle stem cell metabolism is different from other cells of the skin. Cellular metabolism involves the breakdown of the nutrients needed for cells to divide, make energy and respond to their environment. The process of metabolism uses enzymes that alter these nutrients to produce metabolites. As hair follicle stem cells consume the nutrient glucose - a form of sugar - from the bloodstream, they process the glucose to eventually produce a metabolite called pyruvate. The cells then can either send pyruvate to their mitochondria - the part of the cell that creates energy - or can convert pyruvate into another metabolite called lactate. "Our observations about hair follicle stem cell metabolism prompted us to examine whether genetically diminishing the entry of pyruvate into the mitochondria would force hair follicle stem cells to make more lactate, and if that would activate the cells and grow hair more quickly."

The research team first blocked the production of lactate genetically in mice and showed that this prevented hair follicle stem cell activation. Conversely, they increased lactate production genetically in the mice and this accelerated hair follicle stem cell activation, increasing the hair cycle. "Before this, no one knew that increasing or decreasing the lactate would have an effect on hair follicle stem cells. Once we saw how altering lactate production in the mice influenced hair growth, it led us to look for potential drugs that could be applied to the skin and have the same effect."

The team identified two drugs that, when applied to the skin of mice, influenced hair follicle stem cells in distinct ways to promote lactate production. The first drug, called RCGD423, activates a cellular signaling pathway called JAK-Stat, which transmits information from outside the cell to the nucleus of the cell. The research showed that JAK-Stat activation leads to the increased production of lactate and this in turn drives hair follicle stem cell activation and quicker hair growth. The other drug, called UK5099, blocks pyruvate from entering the mitochondria, which forces the production of lactate in the hair follicle stem cells and accelerates hair growth in mice.



Good stuff, at least in this case we have some structures for UK5099
unlike those other studies from the Hopkins osteoarthritus folks that hide them.

But look at that guy, a big fat cyano group right there, (like the cheap B-12 cyano-conjugated mimics, or that amygdalin miracle molecule that one cancer doc was pushing for a while), is that the source of its power? Does it break down and block complex I, or III or other stuff, and therefore just taking the mitos out of the picture?

Posted by: john hewitt at August 16th, 2017 9:59 AM

While lethal causes of aging is undoubtedly more important than superficial nuisances, people who aren't close to death tend to respond most to superficial improvements. I think if we had a reliable treatment that reversed male pattern baldness, or made the average 50 year old look like they're 40 (not in the botox sense), it would be tremendous for longevity's public support. It's the lowest common denominator that everyone can agree on. It would be an existence proof, albeit a shallow one. That can then be the foundation for more comprehensive treatments, from all angles - medically, socially. Harnessing human vanity and ego is one fine way about it, IMO.

Posted by: Bo at August 16th, 2017 1:38 PM

I agree with Bo, superficial improvements are tremendously important if we want to popularize life extension and rejuvenation therapies with the general public. Most people are visual and respond to what they can see, stacks of research papers, figures and data tables won't have the impact of seeing someone they know regain hair.

Posted by: Corbin at August 16th, 2017 2:40 PM

I agree with Bo and Corbin. The money made from such therapies could be used for research on less superficial things.

It might be worth mentioning that I've tried rosemary extract and it seemed to activate hair follicles all over the body. I haven't been this fuzzy since childhood. Unfortunately, I had a rash of spider veins while taking it.

Posted by: CD at August 16th, 2017 3:28 PM

I agree with Bo and Corbin and CD. Aesthetics aside, if we can control follicles to regrow hair we can actually do a lot of very similar things (that won't necessarily have a huge immediate product market) using those exact same priciples. Namely controlling oxidative vs glycolytic vs aerobic glycolytic metabolic state, via reving up or down all or some respiratory complexes and the (as here) the import channels to feed them. Next step to precision hair is controlling the nervous ennervation of the follicle base, and apportioning of whole mitos.

Posted by: john hewitt at August 16th, 2017 3:46 PM

does the extra lactate, a preferred fuel for neurons, attract re-ennervation of the follicle, and if so, re-apportioning of nubile stemlike-inducing mitochondria from the nerves ?

Posted by: john hewitt at August 17th, 2017 7:33 AM

Curiously lactic acid is found in many hair products and hair removers. I wounded what would if one inject lactic acid or lactate subq in the scalp.

Posted by: JohnD at August 18th, 2017 5:53 PM

This is interesting, but not that interesting as it was performed in mice. It really needs to be replicated in a xenograft model- a mouse without a functioning immune system that has had a patch of bald human scalp transplanted onto it.

Scientists have been able to culture mice and rat hair follicle stem cells (dermal papilla cells) for around 30 years and injecting them back into mice and rats induces robust hair growth. But they have not been able to do this with human hair follicle stem cells, and look to have only recently overcome this problem with 3D culture techniques that allow the human cells to retain their character (rat and mice cells naturally clump together and so don't need these 3D culture techniques).

But culturing cells is expensive, so if this research is replicated in xenograft models, it could lead to affordable hair loss treatments.

Posted by: Jim at August 19th, 2017 1:33 PM

Be careful what you wish for...activation of JAK/STAT pathway is associated with SASP/frailty and other unpleasant things...

Posted by: Tom at August 20th, 2017 7:02 AM
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