The Silver Lining: Grey Hairs as Secret Superheroes
As our bodies age, they face different kinds of stresses, and our cells react in different ways, ranging from something as harmless as hair graying to something as serious as melanoma. Both of these changes start from the same type of cells called melanocyte stem cells (McSCs), which help make hair color. Previously, it was determined that sometimes McSCs die off, leading to gray hair, while other times, they grow too much, leading to melanoma. In the study presented, researchers wanted to find out what kind of stresses push the McSCs to each of these outcomes.
To start, the researchers looked at how the McSCs react to different kinds of damage. This started with ionizing radiation (IR), a form of radiation that can cause double-strand breaks in DNA, meaning that DNA is cut on both strands. When McSCs receive this kind of damage, they stop dividing and enter senescence, a sort of “sleep” mode where they no longer grow or divide. They become mature pigment cells and permanently leave the stem cell pool, leading to hair graying. This process is called seno-differentiation. The scientists further demonstrated the importance of the p53-p21 pathway to seno-differentiation, which is a molecular system that stops damaged cells from dividing. When there is more activity in this pathway, graying of hair speeds up.
Then, the researchers shifted their focus to a different kind of stress: carcinogens, which are cancer-causing chemicals. Specifically, they used dimethylbenz(a)anthracene (DMBA) and ultraviolet B (UVB), but surprisingly, they saw that these carcinogens did not cause McSC senescence. Instead, they observed that these carcinogens caused biochemical effects in the production of PGE2, a molecule that helps protect cells, and an increase in arachidonic acid metabolism. This allowed the McSCs to keep dividing even with DNA damage, preventing the depletion of stem cell reserves and thus preventing hair graying.
To start, the researchers looked at how the McSCs react to different kinds of damage. This started with ionizing radiation (IR), a form of radiation that can cause double-strand breaks in DNA, meaning that DNA is cut on both strands. When McSCs receive this kind of damage, they stop dividing and enter senescence, a sort of “sleep” mode where they no longer grow or divide. They become mature pigment cells and permanently leave the stem cell pool, leading to hair graying. This process is called seno-differentiation. The scientists further demonstrated the importance of the p53-p21 pathway to seno-differentiation, which is a molecular system that stops damaged cells from dividing. When there is more activity in this pathway, graying of hair speeds up.
Then, the researchers shifted their focus to a different kind of stress: carcinogens, which are cancer-causing chemicals. Specifically, they used dimethylbenz(a)anthracene (DMBA) and ultraviolet B (UVB), but surprisingly, they saw that these carcinogens did not cause McSC senescence. Instead, they observed that these carcinogens caused biochemical effects in the production of PGE2, a molecule that helps protect cells, and an increase in arachidonic acid metabolism. This allowed the McSCs to keep dividing even with DNA damage, preventing the depletion of stem cell reserves and thus preventing hair graying.
Hair graying results from the depletion of McSCs due to cell senescence
Image Source: Romana Klee
Additionally, they found that there was a molecule called the KIT ligand (KITL), which is made by support cells and acts as a growth signal for McSCs. The introduction of carcinogens caused the support cells to produce more KITL, which also helped McSCs survive and divide. When KITL levels were decreased in mice, hair graying increased, whereas when KITL levels were increased, the stem cells were protected.
However, protection of the stem cell reserve and prevention of McSCs senescence come at the cost of the development of melanoma. When McSCs were not dying after DNA damage, they were more likely to form cancers with the presence of mutations.
This study shows that hair graying and melanoma can come about from different reactions in the same stem cells. Cells can experience severe DNA damage, causing them to shut down, resulting in hair graying. However, if the environment prevents senescence, such as through increased KITL, PGE2 production, or arachidonic acid metabolism, the cells can survive and continue to divide despite DNA errors, increasing the risk of melanoma. Understanding this duality can help explain how aging and cancer are linked and shows us that, at the end of the day, maybe those gray hairs aren’t so bad—they might just be saving you.
However, protection of the stem cell reserve and prevention of McSCs senescence come at the cost of the development of melanoma. When McSCs were not dying after DNA damage, they were more likely to form cancers with the presence of mutations.
This study shows that hair graying and melanoma can come about from different reactions in the same stem cells. Cells can experience severe DNA damage, causing them to shut down, resulting in hair graying. However, if the environment prevents senescence, such as through increased KITL, PGE2 production, or arachidonic acid metabolism, the cells can survive and continue to divide despite DNA errors, increasing the risk of melanoma. Understanding this duality can help explain how aging and cancer are linked and shows us that, at the end of the day, maybe those gray hairs aren’t so bad—they might just be saving you.
Featured Image Source: Dr. Yale Rosen Atlas of Pulmonary Pathology
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