Scientists led by the University of California, Irvine, have identified a mechanism by which aging pigment cells in the skin stimulate hair growth in skin moles, or birthmarks. This study reveals that osteopontin and the CD44 molecule play critical roles in activating hair growth within hairy skin nevus despite the presence of large numbers of senescent pigment cells. . This finding contradicts the commonly held belief that senescent cells, normally associated with the aging process, are detrimental to regeneration.
The results of this study may provide a roadmap for next-generation treatments for male pattern baldness.
Researchers have found that senescent pigment cells in skin moles can stimulate strong hair growth, challenging the idea that these cells impede regeneration. This study showed that the molecules osteopontin and CD44 play a key role in this process and may open up new avenues for treating common hair loss conditions.
A research team led by the University of California, Irvine, has identified the process by which aging or aged pigment-producing cells in the skin cause significant hair growth inside skin moles called nevus. This finding may provide a roadmap to an entirely new generation of molecular therapies for male pattern baldness, a common form of hair loss in both women and men.
The study was published in the journal June 21 Nature, describe the critical role that osteopontin and CD44 molecules play in activating hair growth within hairy skin nevus. These skin nevus accumulate a particularly large number of senescent pigment cells, but still show very strong hair growth.
male pattern baldnessAlso known as male or female pattern baldness, it is the most common type of hair loss that affects both men and women. It is a genetic disorder that causes progressive thinning of hair follicles, resulting in the production of finer, shorter hair over time. In men, it often manifests as a receding hairline and hair loss on the crown of the head, and in women it usually manifests as thinning hair all over, especially on the crown.
“We discovered that senescent pigment cells produce large amounts of a specific signaling molecule called osteopontin, which allows tiny, normally dormant hair follicles to activate stem cells to grow long, thick hair. It will grow,” said lead author Maxim Prix, UCI professor. Developmental and cell biology studies. “Senescent cells are usually thought to be detrimental to regeneration and are thought to accelerate the aging process by accumulating in tissues throughout the body, but our research suggests that cellular aging has a positive side. It clearly shows.”
Hair follicle growth is properly regulated by stem cell activation. These cells divide, allowing the hair follicle to periodically produce new hairs. Each time a hair grows there is a period of dormancy during which the follicle stem cells are inactive until the next cycle begins.
This study included a mouse model with hyperpigmented skin patches in which hair stem cells were hyperactivated and showed enhanced hair growth, clinical observations documented in human hairy skin nevus. was very similar to A more detailed analysis of senescent pigment cells and their nearby hair stem cells shows that the former produce high levels of a signaling molecule called osteopontin, and hair stem cells have a corresponding receptor molecule called CD44. It was revealed. Molecular interactions between osteopontin and CD44 activate hair stem cells, resulting in strong hair growth.
To confirm the key roles of osteopontin and CD44 in this process, mouse models lacking either of these genes were studied. They were found to have noticeably slower hair growth. The effect of osteopontin on hair growth has also been confirmed in human hairy skin nevus samples.
“Our findings provide qualitative new insights into the relationship between senescent cells and the tissue’s own stem cells, revealing positive effects of senescent cells on hair follicle stem cells,” said first author and co-author. Corresponding author Xiao Zhi Wang, associate expert in developmental cell biology at UCI, said. . “As we learn more, that information could be used to develop new therapeutics that target senescent cell properties and treat a wide range of regenerative disorders, including common hair loss.”
The team included medical experts and academics from the United States, China, France, Germany, South Korea, Japan, and Taiwan.
“In addition to osteopontin and CD44, we are further investigating other molecules present in hairy skin nevi and their ability to induce hair growth. Activators may be identified,” Prix said.
Reference: “Signaling by Aging Melanocytes Hyperactivates Hair Growth” Xiaojie Wang, Raul Ramos, Anne Q. Phan, Kosuke Yamahan, Jessica L. Flesher, Shan Jiang, Ji Won Oh, Suoqin Jin, Sohail Jahid , Chen-Hsiang Kuan, Truman Kt Nguyen, Heidi Y. Liang, Nitish Udupi Shettigar, Renzhi Hou, Kevin H. Tran, Andrew Nguyen, Kimberly N. Vu, Jennie L. Phung, Jonard P. Ingal, Katelyn M. Levitt , Xiaoling Cao, Yingzi Liu, Zhili Deng, Nobuhiko Taguchi, Vanessa M. Scafon, Guanghuang Wang, Kara Nicole Paolili, Xiaoyan Wang, Christian F. Guerrero-Juarez, Ryan T. Noelani Greenberg, Roland Luis-Vega, Priya Vasudeva, Ravi Murad, Lili Harida Putri Widyastuti, Hye-Lim Lee, Kevin J. McElwee, Alain-Pierre Gadeau, Devon A. Lawson, Bogi Andersen, Ali Mortazavi, Zhengquan Yu, Qing Nie, Takahiro Kunisada, Michael Karin, Jan Tuckermann, Jeffrey D. Esko, Anand K. Ganesan, Ji Lee, Maxim V. Prix, June 21, 2023, Nature.
DOIs: https://doi.org/10.1038/s41586-023-06172-8
This work was supported in part by LEO Foundation grants LF-AW-RAM-19-400008 and LF-OC-20-000611. Chan Zuckerberg Initiative grant AN-0000000062; WM Keck Foundation grant WMKF-5634988. The National Science Foundation has funded his DMS1951144 and DMS1763272.and National Institutes of Health Grant U01-AR073159, R01-AR079470, R01-AR079150, R21-AR078939, and P30-AR075047. Additional support was from Simons Foundation grant 594598 and California Institute of Regenerative Medicine Shared Research Laboratory Grant CL1-00520-1.2.
