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Common Form of Hair Loss Could Be Reversed by Targeting Aged Skin Pigment Cells

A balding man.
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A research group led by the University of California, Irvine has revealed the mechanisms behind the rampant hair growth observed in skin moles, or nevi. The team has shown that the process is triggered by aging pigment cells. The surprising results turn our understanding of what age means for hair loss on its head and could pave the way for molecular treatments aimed at addressing androgenetic alopecia, a prevalent form of hair loss that affects both men and women.

The study was published in Nature.

The mystery of old and hairy cells

Hairy skin nevi have a puzzling physiology. They have high numbers of aging pigment cells and yet show strong hair growth, contrary to what might be expected in this older cell population. The study points a spotlight on certain signaling molecules as being responsible for the unusual growth.

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Lead corresponding author Maksim Plikus, UCI professor of developmental and cell biology, said, “We found that senescent pigment cells produce large quantities of a specific signaling molecule called osteopontin, which causes normally dormant and diminutive hair follicles to activate their stem cells for robust growth of long and thick hairs. Senescent cells are typically viewed as detrimental to regeneration and are thought to drive the aging process as they accumulate in tissues throughout the body, but our research clearly shows that cellular senescence has a positive side to it.”

Hair follicle growth is carefully orchestrated by the activation of stem cells, which divide to enable follicles to produce new hairs. These hairs form in cycles, with a dormant phase following each episode of hair growth, during which the stem cells of the follicle stay inactive until the commencement of the next cycle.

To analyze the nevi, the team used mouse models with pigmented skin areas exhibiting hyperactivated stem cells and hair growth that mimicked the processes seen in human nevi. The researchers conducted a thorough examination of senescent pigment cells and adjacent hair stem cells. The aging pigment cells released high levels of osteopontin, which paired with a receptor present on the stem cells called CD44. Once osteopontin interacted with CD44, the stem cells activated, kickstarting a hair growth cycle.

New therapies for hair loss

Subsequent studies on mouse models lacking genes coding for either osteopontin or CD44 showed a markedly reduced hair growth rate, substantiating their essential roles. Osteopontin’s effect on hair growth was further validated through samples collected from human hairy skin nevi.

“Our findings provide qualitatively new insights into the relationship between senescent cells and tissue’s own stem cells and reveal positive effects of senescent cells on hair follicle stem cells,” said first and co-corresponding author Xiaojie Wang, UCI associate specialist in developmental and cell biology. “As we learn more, that information can potentially be harnessed to develop new therapies that target properties of senescent cells and treat a wide range of regenerative disorders, including common hair loss.”

Plikus outlined the team’s next avenues of research: “In addition to osteopontin and CD44, we’re looking deeper into other molecules present in hairy skin nevi and their ability to induce hair growth. It’s likely that our continued research will identify additional potent activators.”

Reference: Wang X, Ramos R, Phan AQ, et al. Signalling by senescent melanocytes hyperactivates hair growth. Nature. 2023;618(7966):808-817. doi:10.1038/s41586-023-06172-8

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