Study Identifies A Possible Cause of Age-Induced Hair Loss

Study Identifies A Possible Cause of Age-Induced Hair Loss

Hair follicle aging is driven by transepidermal elimination of stem cells via COL17A1 proteolysis

Researchers show how the normal hair cycle (left) is disrupted by DNA damage (center),
resulting in age-induced hair follicle miniaturization (right)

We have known for decades that the incidence of male pattern baldness increases with age. New research published in the February 2016 edition of the journal Science has shed light on why this is the case. Researchers examining the role of hair follicle stem cells (HFSC) in the hair growth cycle have found that accumulated DNA damage in these cells results in the depletion of a key signaling protein and the progressive miniaturization of the hair follicle (and eventual hair loss). ((Matsumura H, Mohri Y, Binh NT, et al. Hair follicle aging is driven by transepidermal elimination of stem cells via COL17A1 proteolysis. Science. 2016 Feb: Vol. 351, Issue 6273, p. 613.)) The study represents a breakthrough in our understanding of the cell aging process and could open new pathways for the treatment of not only hair loss but other age-related conditions as well.

Background: The Hair Growth Cycle

At any point in time, a hair follicle exists in one of three phases:

Anagen Phase – this is the “growth” phase in which the hair follicle is actively producing living hair. Anagen can last from two to seven years.
Catagen Phase – this is a short transitional phase in which hair growth stops, the middle of the follicle constricts, and the bottom of the follicle begins to form the “club.” The follicle also separates from the bloodstream. Catagen lasts two to three weeks.
Telogen Phase – this is the “resting” phase in which the clubbed hair detaches from the dermal papilla and is susceptible to falling out. Telogen lasts three to four months before hair follicle stem cells initiate a new anagen (growth) phase and the cycle repeats.

Stem Cells and the Hair Cycle

Normally, hair follicle stem cells (HFSC) perpetuate the hair cycle by initiating a new anagen (growth) phase after the telogen (resting) phase. But HFSC, like all cells, age over time. Included in this aging process is damage to DNA strands inside these cells due to spontaneous errors in DNA replication or those due to exposure to sunlight and other insults. While it has been well understood that hair follicle miniaturization occurs as a person ages and that damage to genetic material contributes to the process, the exact mechanism that ties cell aging to the disruption of the normal hair cycle was unknown. The recent study examines miniaturization from cell aging and distinguishes it from miniaturization caused by the effects of DHT.

Results of the Study

The key finding in this new research is that as hair follicle stem cells (HFSC) accumulate genetic damage over time, their store of a signaling protein called COL17A1 is depleted. The depletion of this key protein forces HFSC to differentiate into a common type of skin cell called a keratinocyte. By differentiating into keratinocytes, the population of HFSC gradually shrinks, there are fewer HFSC to initiate the anagen (growth) phase, and the telogen (resting) phase is extended. With a gradually longer telogen phase and shorter anagen phase, the follicle progressively miniaturizes. Eventually, the hair-producing follicle disappears leaving a bald scalp and the keratinocytes, which no longer serve a purpose in the hair growth cycle, are ejected from the skin.¹ Click here to view the graphic that illustrates this process.

The authors of the study suggest that restoring COL17A1 levels, or halting their depletion, may prevent this aging-induced hair follicle miniaturization from occurring.¹

With perhaps much broader significance, the study confirms the tight linkage between the instability of genetic material in stem cells (that can be due to environmental factors) and the shrinkage and functional decline seen in many organs as they age.

Conclusion

Progressive hair loss is a pervasive problem for males as they age. However, current treatments deal, exclusively, with hormone-induced miniaturization. The discovery of the mechanism behind age-induced miniaturization may result in a new avenue for the treatment of hair loss. More research into methods of boosting levels, or preventing the depletion, of COL17A1 may yield a hair loss therapy that targets this cause of hair loss.

Further, developing a better understanding of the cell aging process may open up new avenues of research into the causes of, and potential solutions to, the age-induced decline of major organs in the body.

Image c/o Science

Posted by Robert M. Bernstein M.D.

What is Difference in Hair Cloning Techniques Studied by Aderans and Intercytex?

Q: I know that both Aderans and Intercytex are doing research with cloning hair. Is there any difference in their approaches?

A: Aderans is using the “two-cell” approach. They feel that the best way to produce viable hair follicles is to use a combination of inducer cells and responder cells. Each would be multiplied separately and then injected together into the skin. The inducer cells are follicular fibroblasts and lie at the base of the hair follicle. The responder cells are keratinocytes. They feel that the combination of cells will have the best chance of producing clinically useful hair.

Intercytex prefers a one-cell approach. Their researchers feel that when the cultured inducer fibroblasts are injected into the skin there will be enough existing cells in the skin to produce a cosmetically viable hair. In their experimentation, Intercytex uses a new animal model, termed the “flap graft” model, that involves the implantation of cultured dermal papilla cells with keratinocytes placed under a flap on the back of hairless mice. Later the flap is exteriorized (turned over), allowing the hair to grow normally. Exactly how this will be applied to clinical use in humans is not clear.

A completely different view is held Dr. Ralf Paus at the University of Luebeck in Germany. He feels that there are already enough stem cells in the bald scalp and that the key to hair re-growth is to target key elements in the hair cycle. He feels that topically applied inhibitors of catagen (the resting phase of the hair cycle), exogen (the formation of an empty hair follicle), or inhibitors of the terminal-to-vellus transformation (the process of a hair shrinking in size under the influence of DHT and referred to as miniaturization) will the most effective way to go.

Finasteride and dutasteride are drugs that work in this way, but are clearly not very effective in stimulating new growth. He also feels that an anagen inducer, along the lines of a minoxidil-type medication has a better chance of success then the stem cell targeting strategies described above. In these cases one would, in a sense, rejuvenate dormant hair follicles rather than induce new ones to grow.

Read about Hair Cloning Methods

Posted by Robert M. Bernstein M.D.