Tag: hair loss

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A Trend of Prescribing Oral Minoxidil Off-label for Baldness

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The New York Times reports that low oral doses of the cheap antihypertensive drug minoxidil – a key ingredient in many hair-loss treatments such as Rogaine – is now being widely used as an off-label prescription for male and female hair loss.

Since the accidental discovery of minoxidil’s topical efficacy in treating hair loss in the 1980s, it had became a staple in `Rogaine for male and female patients. However, applying the foam or lotion onto scalps is time-consuming and uncomfortable for many – as well as expensive.

There is not much in the way of clinical evidence as to its efficacy. A 2019 study in the Journal of the American Academy of Dermatology is so far the only randomised open study to compare 1mg oral minoxidil against 5% topical minoxidil for hair loss in female patients.

The oral minoxidil was not inferior to the topical version, and indeed trend analysis suggested it might be more effective.

According to the Times, the off-label designation might scare off some, but such drugs are widely used in practice.

Dermatologist Robert Swerlick, of the Emory University School of Medicine, noted that “most things we [dermatologists] do are off-label because there is nothing on-label.”

Brett King, a Yale School of Medicine dermatologist, told the Times that it would likely stay off-label because there wasn’t a financial incentive for Big Pharma to invest in proper trials.

“Oral minoxidil costs pennies a day,” King told the Times. “There is no incentive to spend tens of millions of dollars to test it in a clinical trial. That study truly is never, ever going to be done.”

Until researchers have the motivation and funding to conduct randomised controlled trials into low-dose oral minoxidil as a baldness treatment, the situation is likely to remain unchanged even if it is growing in popularity with certain dermatologists.

Categories : AgeingTags : Leave a comment

A New Mechanism Explains Hair Loss in Men and Women

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Bald man
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Studies of balding male mice have uncovered a possible cause of hair loss in men and women as well. The findings, published in Nature Aging, provide new insight into how hair and tissues age.

The study shows as hair stem cells age, they lose the adhesion that keeps them lodged inside the hair follicle. As their adhesiveness wanes, the stem cells escape from their location, called the bulge, into the dermis. Once outside their delicate microenvironment, they generally can’t survive.

“The result is fewer and fewer stem cells in the hair follicle to produce hair,” said lead author Rui Yi, the Paul E. Steiner Research Professor of Pathology at Northwestern University Feinberg School of Medicine. “This results in thinning hair and ultimately baldness during ageing.”

This finding could be applicable to older men and women with thinning hair as mice and humans share hair and stem cell similarities, Prof Yi said.

By labelling individual stem cells with a fluorescent marker, the researchers were able, for the first time, to track hair follicle ageing in real time in live animals. Scientists also discovered two key genes responsible for enhancing adhesiveness of the stem cells. They are now trying to reinstate these genes to see if that will reverse hair loss.

During follicles’ normal cycles of life and death, a large number of stem cells remain permanently lodged in the stem cell compartment of hair follicles to keep producing hair follicle cells.

“We believe this stem cell escape mechanism has never been reported before, because nobody could track the aging process in live animals,” Yi said.

Though scientists knew hair follicles become miniaturised during aging, how it happened was unclear. Many thought it was due to cell death or the inability of cells to divide as they age.

“We discovered, at least in part, it is due to hair follicle stem cells migrating away from their niche,” Prof Yi said. “Cell death also occurs during our observation. So, our discovery doesn’t dispute existing theories but provides a new mechanism.”

Source: Northwestern University

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Hair Loss Tied to High-fat Diets or Genetic Obesity

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A mouse study by Japanese researchers found that high-fat diets or genetically induced obesity can cause loss of hair follicles.

Obesity is linked to the development of numerous diseases in humans, such as heart disease and diabetes. However, it’s not fully clear how body organs specifically deteriorate and lose functionality from chronic obesity. Using mice, researchers from Tokyo Medical and Dental University (TMDU) examined how a high-fat diet or genetically induced obesity can affect hair thinning and loss. The findings, published in Nature, indicated that obesity can lead to depletion of hair follicle stem cells (HFSCs) by inducing certain inflammatory signals, blocking hair follicle regeneration and ultimately resulting in loss of hair follicles.

HFSCs normally renew themselves every hair follicle cycle. With progressing age, HFSCs fail to renew themselves leading to fewer HFSCs and therefore hair thinning. Although overweight people have a higher risk of male pattern balding, whether obesity accelerates hair thinning, how it does this and the molecular mechanisms behind it have remained largely a mystery. The TMDU group aimed to address those questions and identified some of the mechanisms.

Explaining the study, study lead author Hironobu Morinaga said: “High-fat diet feeding accelerates hair thinning by depleting HFSCs that replenish mature cells that grow hair, especially in old mice. We compared the gene expression in HFSCs between HFD-fed mice and standard diet-fed mice and traced the fate of those HFSCs after their activation.

“We found that those HFSCs in HFD-fed obesed mice change their fate into the skin surface corneocytes or sebocytes that secrete sebum upon their activation. Those mice show faster hair loss and smaller hair follicles along with depletion of HFSCs.

“Even with HFD feeding in four consecutive days, HFSCs show increased oxidative stress and the signs of epidermal differentiation.”

“The gene expression in HFSCs from the high-fat–fed mice indicated the activation of inflammatory cytokine signaling within HFSCs,” said senior author Emi Nishimura. “The inflammatory signals in HFSCs strikingly repress the Sonic hedgehog signaling that plays a crucial role in hair follicle regeneration in HFSCs.

However, the researchers noted that activating the Sonic hedgehog signaling pathway in this process can rescue the depletion of HFSCs. “This could prevent the hair loss brought on by the high-fat diet,” said Nishimura.

This study shines a light on cellular and tissue dysfunction from a high-fat diet or genetically induced obesity, and could lead to prevention and treatment of hair thinning along with greater understanding of obesity-related diseases.

Source: Tokyo Medical and Dental University

Categories : GeneticsTags : Leave a comment

Researchers Uncover a Mechanism that Regulates Hair Regeneration

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Chinese researchers have discovered a new regulatory mechanism for the regeneration capacity of skin hair, with important clues for developing treatments for hair loss. Hair loss or alopecia is an extremely common condition, yet there is still no effective therapy for it.

In the skin, activation of hair follicle stem cells (HFSCs) and progenitors by growth factor stimulation is the basis for hair follicle and hair regeneration. Hair regeneration defects can often attribute to blunted responses of HFs to growth stimuli, but it is how the sensitivity of HFSCs or progenitors to growth stimuli is determined is still unclear. Figuring out the answer to this question will provide important clues for the treatment of hair-related diseases such as alopecia.

To this end, Prof Zhang Liang’s group from the Shanghai Institute of Nutrition and Health (SINH) of the Chinese Academy of Sciences, and collaborators uncovered the role of the micro RNA miR-24 and its mechanism in limiting the regenerative ability of hair follicle (HF) progenitors, opening up new therapeutic avenue for hair loss treatment. microRNAs regulate key steps of cell differentiation and development through suppressing gene expression in a sequence-specific manner.

The researchers discovered that that the resting-to-activation transition of HF is associated with significant down-regulation of miR-24 in HF progenitors prior to their activation.

By experimenting with mouse models, they found that miR-24 limits the sensitivity of HF progenitors to growth stimuli. miR-24 over-expression in the skin epithelium significantly delayed HF progenitor activation and hair cycle progression, while its conditional ablation significantly accelerated the hair cycle and increased the HFs’ sensitivity to growth stimuli.

Interestingly, the conditional ablation of miR-24 in skin epithelium significantly improved the effect of Minoxidil lotion on stimulating hair growths without detectable side effects, indicating that miR-24 could be a new potential target for hair regeneration therapies.

Mechanistically, the researchers discovered that Plk3 is a new miR-24 target gene that mediates the function of miR-24 to limit hair growth by regulating CCNE1, a key cell cycle regulator. They also found that miR-24 acts downstream bone morphogenetic protein (BMP), which is a known inhibitory signal for hair growth.

The study revealed that miR-24 is a key factor limiting the regenerative ability of skin HF progenitors. How adult stem cells respond appropriately to environmental stimuli is a question of fundamental importance in stem cell biology.

Source: Medical Xpress

Journal information: Fengzhen Liu et al, miR-24 controls the regenerative competence of hair follicle progenitors by targeting Plk3, Cell Reports (2021). DOI: 10.1016/j.celrep.2021.109225