In the process of life, human cells are constantly influenced by various internal and external factors, which can damage DNA. This type of DNA damage is a recognized cause of aging and cancer, but scientists have been struggling to clarify the specific association between the two, especially how DNA damaged stem cells affect tissue health over time.

Melanin stem cells can differentiate into melanocytes, which determine the color of hair and skin. In mammalian bodies, these types of stem cells exist in the prominence subregion of hair follicles. Here, they exist in the form of immature melanocytes, ensuring that hair and skin maintain their original color through repeated regeneration cycles.

A research team led by Emi Nishimura and Yasuaki Mohri from the University of Tokyo in Japan recently published a paper online in Nature Cell Biology, exploring how melanocyte stem cells respond to different types of DNA damage.

Through long-term lineage tracking and gene expression profiling analysis in mice, researchers found that when the DNA double strand of melanocyte stem cells breaks, an aging coupled differentiation process is initiated. In this state, stem cells will permanently mature and eventually disappear, causing hair to turn white. This process is regulated by the activation of the p53-p21 signaling pathway.

When melanocyte stem cells are exposed to specific carcinogens such as 7,12-dimethylbenzo (a) anthracene or ultraviolet radiation, they will no longer follow the protective pathway described above. Even in the presence of DNA damage, these stem cells will avoid aging coupled differentiation and continue to self renew. Under the influence of KIT ligand signaling released from surrounding tissues and epidermis, they undergo clonal amplification. These signals from the microenvironment block protective differentiation responses, pushing stem cells towards a cancer susceptible state.

These findings suggest that the same group of stem cells will follow two opposite fates based on stress type and microenvironment signals - either depletion or expansion, "Nishimura said." This study redefines the relationship between hair whitening and melanoma, that is, the two are not unrelated events, but different outcomes of stem cell stress responses

The researchers emphasize that their findings do not necessarily mean that turning hair white can prevent cancer. On the contrary, aging differentiation is more like a defense mechanism triggered by stress, which can eliminate damaged stem cells before they cause harm. When this protective mechanism fails or is bypassed, those damaged stem cells will survive and may trigger melanoma.

Scientists point out that by revealing the molecular pathways that determine the "protective exhaustion" or "dangerous expansion" of stem cells, this study links tissue aging biology with the mechanisms of cancer development. At the same time, it emphasizes the importance of naturally clearing damaged stem cells through "aging breakdown", a biological process that prevents cancer by sacrificing cells that may become tumors.

(Author Hangzhou Network)