Longevity Briefs: Do Hairy Moles Hold The Secret To Reversing Hair Loss?

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Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

Why is this research important: Moles tend to grow hair, even in older people with advanced hair loss elsewhere on the body. Why does this happen, and can the answer to that question help us reverse age-related hair loss?

Moles form when a pigment-producing cell called a melanocyte goes out of control and starts dividing rapidly. This division is soon stopped, however, when melanocytes reach their replicative limit. They then enter a state called senescence in which they are unable to divide further. Senescent cells may not be able to divide, but they are far from inactive, releasing a variety of chemical signals into their local environment.

Diagram showing the structure of the skin and hair follicle. Skin melanocytes are located in the epidermis of the skin, while hair follicle melanocytes are found in the hair bulb at the base of the hair. Most moles are the result of proliferating melanocytes from the epidermis.
*Image by macrovector on Freepik*

What did the researchers do: In this study, researchers looked at mouse models of congenital (present from birth) and acquired moles. They analysed gene expression in hair follicle stem cells located within moles, and compared this to cells from normal hair follicles. They then analysed compounds that were secreted by senescent melanocytes in these moles and how these compounds affected hair growth.

Key takeaway(s) from this research:

Hair follicle stem cells within moles are hyperactive and grow hair continuously
Senescent melanocytes release a signalling molecule called osteopontin that stimulates hair growth when injected into mouse skin
Osteopontin is also produced in human moles and boosts human hair growth

Gene expression of hair follicle stem cells was altered within moles: these cells usually cycle between periods of activity (during which they divide and grow new hair) and periods of inactivity known as quiescence (in which they do not divide or grow hair, but retain the ability to do so). In moles, these stem cells underwent changes in gene expression that suppressed quiescence and made the cells hyperactive.

Next, they identified a prominent signalling molecule produced by senescent melanocytes called osteopontin. They found that when osteopontin was injected into mouse skin, this was enough to stimulate increased hair growth. However, when the gene for osteopontin or for its receptor was deleted, hair follicle stem cells remained quiescent even in the presence of senescent melanocytes.

So osteopontin appears to be responsible for increased hair growth within moles in mice, but what about humans? The researchers did look at human tissue samples, and found that osteopontin was upregulated in human moles. Not only this, but human hair follicles grafted into mice responded to osteopontin by growing more hair.

While senescent cells are generally undesirable when it comes to ageing, we might be able to learn a lot from them about how to regenerate ageing tissues.