A research team led by the University of California has unveiled the mechanisms behind the abundant hair growth observed in skin moles, or nevi. The study was published in Nature.
The team has demonstrated that the process is triggered by aging pigment cells. The unexpected results challenge our understanding of the relationship between age and hair loss and could pave the way for molecular treatments aimed at addressing androgenetic alopecia, a common form of hair loss that affects both men and women.
Skin moles with excessive hair growth pose a perplexing puzzle. Despite having a high number of aging pigment cells, they exhibit strong hair growth, which defies expectations for this older cell population. The study sheds light on specific signaling molecules responsible for this unusual growth.
The researchers found that senescent pigment cells produce substantial amounts of a specific signaling molecule called osteopontin. This molecule triggers dormant and small hair follicles to activate their stem cells, resulting in robust growth of long and thick hairs. Hair follicle growth is meticulously orchestrated by the activation of stem cells, which divide to enable follicles to produce new hairs. These hairs grow in cycles, with a dormant phase following each episode of hair growth. During this phase, the stem cells of the follicle remain inactive until the next cycle begins.
Senescent cells are typically seen as detrimental to regeneration and are thought to drive the aging process as they accumulate in tissues throughout the body. However, the research clearly demonstrated that cellular senescence could have a positive impact.
To investigate 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 interacted with a receptor present on the stem cells known as CD44. This interaction led to the activation of the stem cells and initiated a hair growth cycle.
Injection of osteopontin or its genetic overexpression was sufficient to induce robust hair growth in mice, whereas germline and conditional deletions of either osteopontin or CD44, its cognate receptor on epithelial hair cells, rescued enhanced hair growth induced by dermal nevus melanocytes. Although broad accumulation of senescent cells, such as upon ageing or genotoxic stress, is detrimental for the regenerative capacity of tissue, signalling by senescent cell clusters can potently enhance the activity of adjacent intact stem cells and stimulate tissue renewal.
These findings offer novel insights into the relationship between senescent cells and the tissue’s own stem cells and reveal positive effects of senescent cells on hair follicle stem cells. This information can potentially be utilized to develop new therapies targeting properties of senescent cells and treating various regenerative disorders, including common hair loss.
In addition to osteopontin and CD44, the authors are delving deeper into other molecules present in hairy skin nevi and their potential to induce hair growth. It is likely that the ongoing research will identify additional potent activators.
Credit: Kalhh, Pixabay
