Hair loss prevented by blocking ancient biological mechanism

A surprise result in a lab experiment has led to the discovery of an ancient biological stress pathway that can trigger cells to stop making what’s needed to grow hair. Scientists believe this opens the door to developing a pre-emptive strike, protecting hair follicles from this process and preventing hair loss.

“We were testing a drug that targets metabolism in human hair follicles to influence how cells generate energy, which based on the work of others, we expected to stimulate stem cells,” said senior author Talveen Purba, Research Fellow at The University of Manchester. “However, we found the opposite was true: Hair growth was instead blocked, as cells, including stem cells, quickly stopped dividing.”

The block was the result of the activation of an ancient biological pathway known as the Integrated Stress Response (ISR). This response gets switched on in cells that are under stress – which can be caused by a host of issues, such as a viral infection or misshapen proteins. When the ISR is triggered, cells can halt normal activity, pumping out fewer proteins to focus instead on dealing with the stressor. This can also result in cell death.

Not surprisingly the ISR is also the focus of research into anti-aging treatments, as well as cancer and neurodegenerative disease therapies.

But what does this have to do with losing your hair? The scientists found that when the ISR pathway was activated in hair follicles, this ‘stasis’ of cells stopped producing the all-important proteins needed for hair growth. As such, blocking this trigger, which also causes mitochondrial dysfunction and a breakdown of communication between cells, could send a ‘business as usual’ message to cells and protect against hair loss.

“When we look at hair follicles under the microscope, it’s striking how consistent the response is between hair follicles from different people,” said study co-author Derek Pye, chief technician of the research group.

While still early days, this accidental discovery of how ISR plays such a key role in cell functioning across diverse lifeforms – from yeast to humans – has researchers now focused on how the mechanism works in people suffering hair loss.

“We’re incredibly hopeful as we believe the activation of this pathway could play an important biological role in restricting hair growth in people with hair loss conditions, meaning that targeting it could lead to new treatments,” said Purba.

“As we show that the activation of the ISR is linked to a proliferative block in the human hair follicle, we hypothesize that the ISR could be aberrantly activated in hair disorders to disrupt normal hair follicle cycling by promoting dystrophic anagen,or catagen,” the researchers noted in the study. “As such, targeting this pathway to mitigate ISR activation (e.g. using ISRIB) could be used to help maintain hair follicles in anagen.”

The study was published in the journal PLOS One.

Source: The University of Manchester

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