Hair Raising News

Your hair can 'smell', and it just might like the scent of sandalwood

Dear Readers, we have yet to cover the topic of what covers our heads. Found some surprising findings to share, sure to raise your eyebrows, at least.

Structure of the hair: hair follicle and hair shaft (modified photo from Freepik).

Grow Your Hair with Perfume

I always liked sandalwood perfume - would mix it with lemon verbeena and musk for a personalized scent. Mmmmm. Maybe that’s why I usually sport a lion’s mane in place of what some call a hairdo.

A screening survey searching for compounds that can stimulate hair growth (prolonging anagen and/or inhibiting premature catagen development) found a potent agent - synthetic sandalwood scent! Yes, stimulation of the OLFACTORY RECEPTOR OR2AT4 with sandalwood sets in motion the molecular cascade that leads to elongation of the hair follicle. Obviously, it must be mimicking an endogenous substance, still to be identified [microbiome metabolites high on list]. But, I predict that all hair products will be infused with that scent in the near future. Hope no one is allergic to the smell.

Proposed mechanism of action of OR2AT4 activation by Sandalore® and (unknown) endogenous ligand(s) in human hair follicle epithelium. The activation of OR2AT4 at the cell surface of outer root sheath keratinocytes (ORS KCs; location:see green cells in the central HF cartoon) by endogenous ligands and/or Sandalore® upregulates the expression of genes and kinases involved in programmed cell death, thus preventing intrafollicular apoptosis (e.g.,by phosphorylation of PRAS40 preventing its interaction with mTOR1, upregulation of NF-κB pathway) or downregulates key players in the apoptotic machinery (e.g., dephosphorylation of p53, downregulation of Bad). In parallel, OR2AT4 activation by exogenous (Sandalore®) or endogenous ligands (e.g., metabolites of the HF microbiome) induces the upregulation of PAPPA that cleave the IGFBP4/IGF1 complex to release IGF-1 (pink arrows). The released IGF-1 triggers the activation of IGF-1R on the same cell (autocrine signaling, purple arrow) or on hair matrix keratinocytes (HM KCs; orange “cell”) (paracrine signaling, orange arrow). The activation of IGF-Rs on HM keratinocytes then induces signaling cascades (e.g., PI3K/AKT and/or p38a/ERK1/2/MSK1/2) that activate different transcription factors and particularly CREB, which results in an anti-apoptotic effect and prolonged anagen phase in human HFs. - J Chéret, et al

Reversing Turning Grey

Another hair raising event is the seemingly immediate change of hair color to grey after trauma and fright. Good news - recent evidence shows it can be reversed. It relates to their energy generators, mitochondria.

Here, we develop an approach to profile hair pigmentation patterns (HPPs) along individual human hair shafts, producing quantifiable physical time scales of rapid greying transitions.
Results: Using this method, we show white/grey hairs that naturally regain pigmentation across sex, ethnicities, ages, and body regions, thereby quantitatively defining the reversibility of greying in humans. Molecularly, grey hairs upregulate proteins related to energy metabolism, mitochondria,
and antioxidant defenses. Combining HPP profiling and proteomics on single hairs, we also report hair greying and reversal that can occur in parallel with psychological stressors. - AM Rosenberg et al

I guess if one goes on a calming spiritual retreat, there is a possibility of coming back with fewer platinum plaits. There is a caveat though; the hair greying due to aging is less likely to be reversed, even with near coma inducing calmness.

Balding Factors

In human bodies, testosterone acts as a pre-hormone and the response to testosterone is determined by which metabolic pathway predominates. If it is converted to estrogen via aromatase, it is not going to be hanging around to bind to androgen receptors, or get converted to DHT (dihydrotestosterone), another potent androgen.

Skin hair follicles contain aromatase enzyme, especially in women. Higher levels of aromatase in the frontotemporal scalp regions for women explains the difference in androgenic balding patterns between the two genders. But if aromatase is inhibited at the hair follicle, it leads to virilization, such as androgenic alopecia or virilized facial hair growth (hirsuitism). These complications are actually reported in patients taking aromatase inhibiting agents, e.g. for breast cancer or to treat fungal infections.

Yet another reason to watch out for aromatase inhibitors creeping into your lifestyle.

Recession of the frontal and parietal hairlines and diffuse hair loss (Figure 1a and b) were observed. Miniaturization of follicles in the fronto-temporal area (Figure 1c) was revealed. Behind the scalp area sensible to aromatase, in the frontal region, the diameter of hair was normal without any alterations, with normal hair density (Figure 1d).

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REFERENCES

J Chéret, et al. Olfactory receptor OR2AT4 regulates human hair growth https://www.nature.com/articles/s41467-018-05973-0

AM Rosenberg et al, Quantitative mapping of human hair greying and reversal in relation to life stress, eLife (2021). DOI: 10.7554/eLife.67437 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219384/

https://www.healthcentral.com/article/arimidex-and-hair-loss-a-surprising-side-effect

Gallicchio, L., Calhoun, C. & Helzlsouer, K.J. Aromatase inhibitor therapy and hair loss among breast cancer survivors. Breast Cancer Res Treat 142, 435–443 (2013). https://doi.org/10.1007/s10549-013-2744-2

Hormonal Effects on Hair Follicles https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7432488/

PATENT Composition and method of alleviating adverse side effects and/or enhancing efficacy of agents that inhibit aromatase. https://www.researchgate.net/publication/295699511_Composition_and_method_of_alleviating_adverse_side_effects_andor_enhancing_efficacy_of_agents_that_inhibit_aromatase

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