Throughout our lives, our cells are exposed to environmental and internal factors that can damage our DNA. This damage is known to contribute to aging and cancer, but researchers have not yet understood exactly how damaged stem cells can affect long-term tissue health.
Melanocyte stem cells (McSCs) are found in hair follicles and produce mature melanocytes responsible for hair and skin color.
In mammals, these cells are found in the bulge and peri-bulge regions of hair follicles, and maintain color through continuous cyclic renewal.
The researchers used long-term lineage tracing (a technique for tracking cells over a long period of time) and gene analysis in mice to study the response of stem cells to DNA damage.
They found that double-strand breaks in DNA lead to what is known as "senescence-associated differentiation" (senescence), a process in which cells permanently change themselves and are then lost, causing hair to turn gray.
This process occurs through a molecular pathway called p53-p21, which serves as a protective mechanism to remove harmful cells.
When MCSCs are exposed to certain carcinogens, such as 7,12-dimethylbenz(a)anthracene or UVB radiation, the cells bypass this protective pathway.
Instead of dying or differentiating, they maintain their ability to self-renew and proliferate, a process supported by the KIT signal from the surrounding environment within the skin. This makes the cells more susceptible to tumor formation.
"The same stem cells can follow different fates—either exhaustion or expansion—depending on the type of stress and environmental signals," says Professor Emi Nishimura. "Hair graying and skin cancer are not separate events, but rather the result of different stem cell responses."
The study demonstrates that "senescence-associated differentiation" is not just a cause of gray hair, but rather the body's way of eliminating potentially harmful cells. When this mechanism is bypassed, continued damage to MCSCs may increase the risk of skin cancer.
By studying the molecular pathways that control the fate of melanocyte stem cells, researchers link tissue aging to cancer, showing how natural degeneration can protect the body from the development of tumors.
This discovery represents an important step toward understanding the interaction of aging with cancer at the molecular level, and may pave the way for developing future preventive strategies.
The study was published in the journal Nature Cell Biology.
