October 2025, a team led by Professor Emi Nishimura from the University of Tokyo collaborated with the RIKEN Institute and published a groundbreaking study in the top journal "Nature Cell Biology" — "Antagonistic stem cell fates under stress govern decisions between hair greying and melanoma". This research first reveals that stress-induced grey hair is not merely a sign of aging, but a protective mechanism against skin cancer, opening a new perspective for understanding the relationship between aging and cancer.

1. The "Pigment Reserve Troops" in the Hair Follicle: Melanocyte Stem Cells

To understand this story, we must first get to know the protagonist — melanocyte stem cells (McSC). They reside in the "bulge" area of the hair follicle, like pigment reserves in a factory: when the hair enters the growth phase, some stem cells differentiate into mature melanocytes, producing melanin to "color" the hair; others remain self-replicating, maintaining the stability of the reserve pool.

These stem cells endure pressure throughout their lives: ultraviolet radiation, environmental pollution, and psychological stress can all cause DNA damage. Research has found that after damage, the stem cells face two fate paths, directly determining whether they grow grey hair or develop cancer.

2. Life and Death Decision: The "Teeter-Totter" Between Grey Hair and Cancer

1. Cytotoxic Stress: The Path Leading to "Self-Sacrifice" and Grey Hair

When stem cells encounter strong stress such as radiotherapy or chemotherapy, DNA double-strand breaks occur. Researchers discovered through live tracking technology that the damaged cells do not proliferate wildly, but instead activate the "senescence-differentiation" program: stopping division (senescence) while accelerating differentiation into mature pigment cells, simultaneously expressing senescence markers p21 and melanin.

This is like a damaged machine in a factory: to avoid explosion risk, the manager lets it complete the last batch of production in safe mode before scrapping it. These "senescent pigment cells" provide short-term pigment supply, then are cleared by the body, leading to depletion of the stem cell pool, resulting in grey hair, but eliminating the potential source of cancer.

2. Carcinogenic Stress: The Dangerous Shortcut to Cancer

But when stem cells come into contact with UVB, carcinogens such as DMBA, the plot turns around. These substances also cause DNA damage, yet prevent grey hair from forming: they activate KIT ligand (KITL) in the hair follicle microenvironment. This protein acts as a "survival instruction," allowing damaged stem cells to continue self-renewing, even migrating to the skin surface to form pigmented spots, which may eventually develop into melanoma.

Experiments show that in mice prone to melanoma, the area induced by radiotherapy to grow grey hair almost never developed tumors, whereas the UVB-irradiated area showed significantly increased tumor risk, confirming the "teeter-totter" effect between grey hair and cancer.

3. The Fate Switch: Ultimate Revelation of Molecular Mechanisms

Why do the same pressures lead to different outcomes? The answer lies in two key signaling pathways:

The Grey Hair Pathway: Radiation and other stresses activate the p53-p21 signaling axis within the cell, like triggering a "self-destruction program," forcing damaged cells to undergo senescence and differentiation;

The Cancer Pathway: Carcinogens promote the secretion of KITL in the microenvironment through the arachidonic acid metabolic pathway. This signal "hijacks" the stem cell fate, suppressing the p21 pathway while activating the radiation protection effect of prostaglandin E2, allowing damaged cells to escape elimination.

Researchers further validated this through gene editing experiments: knocking out the KITL gene caused mice to grow grey hair, and carcinogens could no longer protect stem cells; overexpression of KITL successfully prevented grey hair formation.

4. Scientific Insights That Challenge Conventional Beliefs

This study breaks the conventional concept that "aging is decline": grey hair is actually an "anti-cancer alarm" evolved by the body. As age increases, the reduction of supporting factors like KITL in the hair follicle microenvironment leads to more grey hair, and at the same time, the risk of melanoma decreases, which aligns perfectly with clinical observations.

More importantly, it provides a new approach for cancer prevention and treatment. In the future, it might be possible to regulate the KITL signaling or the arachidonic acid metabolic pathway to find a balance between "preserving black hair" and "preventing cancer", such as developing drugs that induce damaged stem cells to follow the "senescence-differentiation" path, reducing cancer risk while minimizing grey hair.

Conclusion

The next time you notice new grey hair, perhaps there's no need to worry. It might be a "cancer-fighting medal" from your body, a self-sacrifice made by stem cells to protect the body. This study shows us that many signs of aging are not inevitable decline, but wise choices made by life to deal with crises.

Original: https://www.toutiao.com/article/7562003524394025512/

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