Have we maybe finally found a solution to deal with scalp hair loss?
"... scientists have linked one of the ways that cells respond to stressful conditions with restricted healthy hair growth.
The ... team unexpectedly discovered the link in a lab experiment where they were testing a drug to see if it cultivates human scalp hair follicles in a dish.
The study inadvertently led to a link to the cellular stress response - an ancient biological mechanism which occurs across life from yeast and roundworms through to humans.
The team hope that by targeting the pathway, treatments for hair loss might one day be found.
Known in full as the Integrated Stress Response- or ISR- it is triggered in stressful cellular conditions such as poor nutrient availability, viral infection, or when there is a build-up of misshaped proteins in cells. ...
Known in full as the Integrated Stress Response- or ISR- it is triggered in stressful cellular conditions such as poor nutrient availability, viral infection, or when there is a build-up of misshaped proteins in cells. ...
ISR is already the subject of great interest to scientists studying cancer, neurodegenerative disorders and ageing. ..."
From the abstract:
"Unravelling how energy metabolism and stress responses are regulated in human scalp hair follicles could reveal novel insights into the controls of hair growth and provide new targets to manage hair loss disorders. The Mitochondrial Pyruvate Carrier (MPC) imports pyruvate, produced via glycolysis, into the mitochondria, fuelling the TCA cycle. Previous work has shown that MPC inhibition promotes lactate generation, which activates murine epithelial hair follicle stem cells (eHFSCs). However, by pharmacologically targeting the MPC in short-term human hair follicle ex vivo organ culture experiments using UK-5099, we induced metabolic stress-responsive proliferative arrest throughout the human hair follicle epithelium, including within Keratin 15+ eHFSCs. Through transcriptomics, MPC inhibition was shown to promote a gene expression signature indicative of disrupted FGF, IGF, TGFβ and WNT signalling, mitochondrial dysfunction, and activation of the integrated stress response (ISR), which can arrest cell cycle progression. The ISR, mediated by the transcription factor ATF4, is activated by stressors including amino acid deprivation and ER stress, consistent with MPC inhibition within our model. Using RNAScope, we confirmed the upregulation of both ATF4 and the highly upregulated ATF4-target gene ADM2 on human hair follicle tissue sections in situ. Moreover, treatment with the ISR inhibitor ISRIB attenuated both the upregulation of ADM2 and the proliferative block imposed via MPC inhibition. Together, this work reveals how the human hair follicle, as a complex and metabolically active human tissue system, can dynamically adapt to metabolic stress."
Surprising link between ancient biology and restricted human hair growth found (original news release)
A healthy hair follicle (left), and one inhibited by a drug that triggered the ISR mechanism preventing hair growth
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