As the old adage goes, what doesn’t kill us makes us stronger. In some cases, it may also be the cause of our graying hair. For the first time, scientists have pinpointed exactly how stress in the body causes our hair to turn gray. "Everyone has an anecdote to share about how stress affects their body, particularly in their skin and hair – the only tissues we can see from the outside," said senior author Ya-Chieh Hsu, Alvin and Esta Star Associate Professor of Stem Cell and Regenerative Biology at Harvard, in a statement. "We wanted to understand if this connection is true, and if so, how stress leads to changes in diverse tissues. Hair pigmentation is such an accessible and tractable system to start with – and besides, we were genuinely curious to see if stress indeed leads to hair graying." Hair doesn't turn gray so much as it loses its pigmentation, a process scientists call canities or achromotrichia, which can be greatly accelerated by acute stress or severe trauma. Harvard University researchers came to this conclusion somewhat serendipitously after conducting pain experiments on mice. They found that when given a substance called resiniferatoxin to induce pain, the animals' fur turned completely white within one month. The experiment was then repeated several times using resiniferatoxin, which is a naturally occurring chemical found in a cactus-like plant native to Morocco, write the authors in Nature. To find out more about how stress impacts the body, specifically the hair, the researchers then began a whole-body analysis to determine which system was responsible for connecting stress to hair color, narrowing it down to the molecular level. They determined that stress activates the sympathetic nervous system – which is responsible for our fight-or-flight response – which in turn causes permanent damage to the stem cells in hair follicles responsible for regenerating pigments. These stem cells act as a reservoir of cells that will one day take on the role of producing pigment, but stress breaks its levees. Image comparing mice subjected to pain-inducing experiment, which resulted in loss of pigmentation [bottom], to dark-colored mice in the control group. William A. Gonçalves Sympathetic nerves branch into hair follicles in the skin, but stressful events cause these to release a chemical known as norepinephrine, or noradrenaline. Norepinephrine overstimulates reserved stem cells and excessively converts them into pigment-producing cells, depleting the stockpile. Scientists next targeted the sympathetic nervous system as a way to inhibit achromotrichia. "After injecting resiniferatoxin into the mice, we treated them with guanethidine, an anti-hypertensive capable of inhibiting neurotransmission via sympathetic fibers. We observed that the process of fur color loss was blocked by the treatment," said study co-author Thiago Mattar Cunha of the University of São Paulo in a statement. Neurotransmission was interrupted, preventing melanocyte stem cell differentiation and preventing fur color loss. Genetically modified mice further confirmed the finding. But how does this impact humans? To find out, researchers treated a culture of human melanocytes with noradrenaline and found that a gene that encodes proteins called cyclin-dependent kinase (CDK) – whose expression was mostly altered after stress induction in mice – similarly saw an increase in expression. "When we started to study this, I expected that stress was bad for the body – but the detrimental impact of stress that we discovered was beyond what I imagined," said Hsu. "After just a few days, all of the pigment-regenerating stem cells were lost. Once they're gone, you can't regenerate pigment anymore. The damage is permanent." The exact mechanisms behind these interactions remain unknown, but the researchers say that they advance our understanding of how stress can impact the body and its organs and tissues. The researchers conclude that they now know that neurons can regulate stem cells, but finding out the extent of this will require future research. Elaborate sympathetic innervation (magenta) around melanocyte stem cells (yellow). Hsu Laboratory, Harvard University Source
