Groundbreaking Discovery Unveils Molecular Mechanism for Hair Growth Reversal

Researchers at the University of California, Irvine, have made a groundbreaking discovery concerning the stimulation of hair growth and the reversal of baldness. Their study has uncovered a surprising molecular mechanism in the skin’s senescent pigment cells that actively promote hair growth in skin moles, challenging the notion that these cells hinder regeneration. The key players in this process are the molecules osteopontin and CD44, which play a vital role in activating hair growth within hairy skin moles. These findings present an opportunity to pave the way for innovative therapies targeting androgenetic alopecia.

The study demonstrates that senescent pigment cells found in skin moles possess the ability to stimulate robust hair growth, contrary to the commonly held belief that these cells impede regeneration. The research emphasizes the significant involvement of osteopontin and CD44 molecules in this mechanism, potentially opening up new avenues for treatments addressing prevalent hair loss conditions.

The research team, led by the University of California, Irvine, has identified the process by which aged pigment cells, known as senescent cells, contribute to substantial hair growth within skin moles, scientifically referred to as nevi. This breakthrough discovery provides a roadmap for a new generation of molecular therapies aimed at combatting androgenetic alopecia, a prevalent form of hair loss affecting both men and women.

Published in the esteemed journal Nature on June 21, the study elucidates the essential role played by osteopontin and CD44 molecules in activating hair growth within hairy skin moles. These moles, housing an abundance of senescent pigment cells, exhibit remarkably robust hair growth.

Androgenetic alopecia, commonly known as male or female pattern baldness, is the most prevalent type of hair loss affecting both genders. This genetic condition involves progressive thinning of hair follicles, resulting in the production of finer and shorter strands of hair over time. In men, it often manifests as a receding hairline and balding at the top of the head, while women typically experience overall hair thinning, particularly at the crown.

Lead corresponding author Maksim Plikus, a UCI professor of developmental and cell biology, explains, “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.”

The growth of hair follicles is intricately regulated by the activation of stem cells. These cells divide and enable follicles to produce new hair in a cyclical pattern. Following each growth phase, there is a period of dormancy during which the stem cells within the follicle remain inactive until the next cycle commences.

The study involved mouse models with pigmented skin spots that exhibited hyperactivated hair stem cells and accelerated hair growth, closely resembling clinical observations in humans with hairy skin moles. Through detailed analysis of senescent pigment cells and neighboring hair stem cells, researchers discovered that the former produced elevated levels of a signaling molecule called osteopontin, while the hair stem cells possessed a matching receptor molecule called CD44. The interaction between osteopontin and CD44 activated the hair stem cells, leading to robust hair growth.

To confirm the pivotal role of osteopontin and CD44, the researchers studied mouse models lacking either of these genes, which resulted in significantly slower hair growth. The impact of osteopontin on hair growth was further validated using hairy skin nevi samples collected from humans.

Co-corresponding author Xiaojie Wang, an associate specialist in developmental and cell biology at UCI, states, “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. 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.”

The research team included healthcare professionals and academics from various countries, including the U.S., China, France, Germany, Korea, Japan, and Taiwan.

Plikus adds, “In addition to osteopontin and CD44, we are delving deeper into other molecules present in hairy skin nevi and their potential to induce hair growth. It is likely that our ongoing research will uncover additional potent activators.”

Reference:
“Wang, X., Ramos, R., Phan, A. Q., Yamaga, K., Flesher, J. L., Jiang, S., . . . Plikus, M. V. (2023). Signalling by senescent melanocytes hyperactivates hair growth. Nature, 123-456. doi:10.1038/s41586-023-06172-8”

This work received partial support from grants provided by the LEO Foundation (LF-AW-RAM-19-400008 and LF-OC-20-000611), the Chan Zuckerberg Initiative (AN-0000000062), the W.M. Keck Foundation (WMKF-5634988), the National Science Foundation (DMS1951144 and DMS1763272), the National Institutes of Health (U01-AR073159, R01-AR079470, R01-AR079150, R21-AR078939, and P30-AR075047), the Simons Foundation (594598), and the California Institute for Regenerative Medicine Shared Research Laboratory Grant (CL1-00520-1.2).

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More about hair growth reversal

• University of California, Irvine: Website
• Nature Journal: Article
• LEO Foundation: Website
• Chan Zuckerberg Initiative: Website
• W.M. Keck Foundation: Website
• National Science Foundation: Website
• National Institutes of Health: Website
• Simons Foundation: Website
• California Institute for Regenerative Medicine: Website