A team of researchers led by the University of California, Irvine, has discovered how senescent (aged) pigment-making cells in the skin cause nevi, or skin moles, to have significant hair growth. The disclosure might offer a guide for a completely new age of sub-atomic treatments for androgenetic alopecia, a typical type of balding in all kinds of people.
The study, which was published today in the journal Nature, explains how the molecules osteopontin and CD44 activate hair growth in nevi with hairy skin. Despite displaying extremely robust hair growth, these skin nevi accumulate particularly large numbers of senescent pigment cells.
Lead co-author Maksim Plikus, a developmental and cell biology professor at the University of California, Irvine, stated, “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.” Our research clearly demonstrates that cellular senescence has a positive side, despite the fact that senescent cells are typically thought to be harmful to regeneration and to be the driving force behind the aging process as they accumulate in tissues throughout the body.”
“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,”
Lead corresponding author Maksim Plikus, UCI professor of developmental and cell biology.
Stem cell activation tightly regulates hair follicle growth. These cells divide, allowing follicles to cycle and produce new hair. There is a dormancy period following each hair growth phase, during which the follicle’s stem cells are inactive until the next cycle begins.
The mouse models used in the study had spots on their skin that were pigmented. They also had hyperactivated hair stem cells and grew hair faster, which was very similar to what doctors have seen with hairy skin nevi in humans. A more in-depth examination of the senescent pigment cells and the nearby hair stem cells revealed that the former produced a signaling molecule called osteopontin in high quantities, and the hair stem cells had a CD44-corresponding receptor molecule. Hair stem cells were activated as a result of the molecular interaction between CD44 and osteopontin, which led to robust hair growth.
In order to verify that CD44 and osteopontin play a leading role in the process, mouse models lacking either of these genes were examined. They had significantly slower hair follicle development. Human hairy skin nevi samples have also confirmed the effect that osteopontin has on hair growth.
“Our findings reveal positive effects of senescent cells on hair follicle stem cells and provide qualitatively new insights into the relationship between senescent cells and the tissue’s own stem cells,” said first author and co-corresponding author Xiaojie Wang, an associate specialist in developmental and cell biology at UCI. That information may be used to develop new therapies that target the properties of senescent cells and treat a wide range of regenerative disorders, including common hair loss, as more information becomes available.
Academics and healthcare professionals from the United States, China, France, Germany, Korea, Japan, and Taiwan made up the team.
“In addition to osteopontin and CD44, we are investigating additional molecules found in nevi with hairy skin and their capacity to stimulate hair growth.” Plikus stated, “It is likely that our ongoing research will identify additional potent activators.”
More information: Xiaojie Wang et al, Signalling by senescent melanocytes hyperactivates hair growth, Nature (2023). DOI: 10.1038/s41586-023-06172-8
