Scientists have just found a surprising link between gray hair and cancer

Melanocyte stem cells (McSCs) are specialized cells that give rise to melanocytes, the pigment-producing cells responsible for hair and skin color. In mammals, these stem cells are located in an area of ​​the hair follicle known as the infrabulbar zone. Here, they exist as immature melanocytes, ensuring that hair and skin retain their color through repeated renewal cycles.

Discover how DNA damage leads to graying of hair

Published online October 6, 2025 Normal cell biologya study conducted by Professor Emi Nishimura and Assistant Professor Yasuaki Mohri at the University of Tokyo explored how cancer stem cells react to different types of DNA damage. Using long-term lineage tracing and gene expression profiling in mice, researchers discovered that when MSCs experience a double-strand break in their DNA, they undergo a process known as senescence-associated differentiation (senescence-associated differentiation). In this case, the stem cells permanently mature and are eventually lost, causing the hair to turn grey. The process is controlled by activation of the p53-p21 signaling pathway.

When cancer stem cells are exposed to certain carcinogens, including 7,12-dimethylbenz(a)anthracene or UVB, they do not follow the same protective pathway. Even in the presence of DNA damage, these cells avoid genetic differentiation and continue to renew themselves. They expand clonally instead, aided by KIT ligand signals released from surrounding tissue and epidermis. These niche-derived signals block the protective differentiation response, driving stem cells toward a cancer-prone state.

Opposition to cellular destinies: gray hair or cancer

According to Nishimura, “These results reveal that the same population of stem cells can follow opposing fates – exhaustion or expansion – depending on the type of stress and the precise environmental signals.” “It reframes graying of hair and melanoma not as unrelated events, but as divergent outcomes of stem cell stress responses,” she adds.

The researchers stress that their findings do not mean that growing gray hair prevents cancer. Instead, dental differentiation appears to function as a stress-induced defense mechanism, removing damaged stem cells before they become harmful. When this protection fails or is bypassed, these damaged cells can survive and possibly lead to skin cancer.

Linking aging, cancer and cellular self-destruction

By revealing the molecular pathways that determine whether stem cells undergo protective exhaustion or dangerous expansion, this study links the biology of tissue aging and cancer formation. It also highlights the value of naturally removing at-risk stem cells through “senolysis,” a biological process that helps prevent cancer by sacrificing cells that could become malignant.

EKN is supported by a JSPS Grant-in-Aid for Scientific Research (S) (25H00439), an AMED CREST project (JP22gm1710003-JP25gm1710003), an AMED project to elucidate and monitor the mechanisms of aging and longevity (JP17gm5010002-JP21gm5010002), and the Amed Skarda Japan Initiative For World Leading Vaccine Research and Development Centers (JP223fa627001), JSPS Grant-in-Aid for Scientific Research (A) (20H00532), and JSPS Grant-in-Aid for Scientific Research in the Innovative Areas “Stem Cell Aging and Diseases” (26115003), international joint research projects have been selected for FY 2025 (No.: K25-1185).

Yasuaki Mohri is supported by a JSPS Grant-in-Aid for Young Scientists (18K15114) and a JSPS Grant-in-Aid for Scientific Research (C) (25K10315).

Jun Seita is supported by the AMED Project to Elucidate and Monitor the Mechanisms of Aging and Longevity (JP19gm5010003, JP20gm5010003) and a JSPS Grant-in-Aid for Scientific Research (C) (18K08377).