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One of the ways our cells respond to stressful situations is by restricting healthy hair growth, according to new research.
Given that activation of this cellular response, known as the integrated stress response (ISR), is associated with a growth block in human hair follicles, researchers at the University of Manchester targeted this pathway to inhibit ISR activation. Relieving hair loss can help maintain hair follicles and treat hair loss.
The study was published in the journal PLOS ONE.
unexpected discovery
The Manchester Hair Research Group discovered a link between ISR activation and hair growth in an experiment to test whether a drug would culture human scalp hair follicles in a dish.
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“We were testing a drug that targets the metabolism of human hair follicles to influence how cells produce energy. Based on work by other researchers, , we expected it to stimulate stem cells,” said Dr Talveen Purba, a researcher at the University of Manchester. and senior author of the study. “But we found that the opposite was true: cells, including stem cells, quickly stopped dividing, so hair growth was actually stunted.”
To further investigate, the researchers performed transcriptomic analysis and found that mitochondrial pyruvate carrier (MPC) inhibition by the targeted drugs resulted in disruption of cell signaling, mitochondrial dysfunction, and activation of ISR gene expression. It was found to promote signs.
What is the integrated stress response (ISR)?
ISR is an ancient biological response that occurs throughout living organisms. To adapt and cope with stressful situations, cells can stop their normal activities by reducing protein production and entering a state of partial quiescence. This can be caused by conditions such as a lack of nutrients, a viral infection, or a buildup of abnormally shaped proteins within the cell. Targeting ISRs is already of interest to scientists studying cancer, neurodegenerative diseases, and aging.
Using RNAScope, researchers confirmed upregulation of ATF4, a transcription factor that mediates ISR, and ATF4 target gene ADM2 in situ on human hair follicle tissue sections.
Furthermore, treatment with the ISR inhibitor ISRIB reduced both the upregulation of ADM2 and the proliferative hair growth block imposed by MPC inhibition.
The researchers highlighted that when looking at hair follicles under a microscope, the responses between hair follicles in different people were surprisingly consistent.
“This study shows how the human hair follicle, as a highly complex mini-organ, can sense and dynamically adapt to changes in nutrient availability and redox homeostasis.” said the people.
Following this study, the authors believe that further investigation of ISR in human hair follicles may reveal new insights into human hair growth, hair loss disorders, tissue metabolism and aging. I’m looking forward to it.
Researchers hope that targeted activation of this pathway could lead to new treatments for individuals with hair loss conditions such as alopecia. However, there are limitations to researchers’ ability to achieve this using ISRIB, and further studies are needed to test the feasibility of blocking ISR activation in hair follicles.
References: Pye D, Scholey R, Ung S, Dawson M, Shahmalak A, Purba TS. Activation of an integrated stress response in human hair follicles. Pro Swan. 2024;19(6):e0303742. doi: 10.1371/journal.pone.0303742
This article is a re-edited version of the press release. Material has been edited for length and content.
