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How do we reverse the greying of the hair?

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Jamila
Jamila Aug 28, 2020
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Necessity

Is the problem still unsolved?

Conciseness

Is it concisely described?

Can we come up with effective therapies for reversing the graying of hair?

Greying of the hair which is also known as canities or achromotrichia is a characteristic of aging and occurs due to the dysregulation of melanogenesis, a complicated process whereby melanocytes produce melanin (the natural pigment in the body).

The hair begins to lose pigmentation from the mid-30s onwards (but this does vary depending on ethnicity). There is also premature hair greying; this is when the hair becomes grey before the age of 30.

Individuals with grey hair may use artificial dyes to temporarily restore the colour of their hair. However, this is not a permanent solution nor does it address the underlying causes of hair greying.

So are there any methods that could be used to overcome this problem in the future?




[1]Seiberg, M. "Age‐induced hair greying–the multiple effects of oxidative stress." International journal of cosmetic science 35.6 (2013): 532-538.

[2]Kumar, Anagha Bangalore, Huma Shamim, and Umashankar Nagaraju. "Premature graying of hair: review with updates." International journal of trichology 10.5 (2018): 198.

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Creative contributions

Stem cell based therapies for hair regeneration

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Subash Chapagain
Subash Chapagain Sep 09, 2020
One of the emerging strategies for hair regeneration is to recover or replenish the signals responsible for hair development by the use of stem cells. Out of many, the following two strategies using stem cells hold the strongest prospects: 1. Conditioned Medium derived from stem cell culture Recently, “Conditioned Medium”, the nutrient medium containing the abundant stem cell secretome has emerged as a possible therapeutic solution for hair regeneration [1]. Stem cell-derived CM is rich in a number of paracrine factors that can be explored as hair regenerative medicine. The factors that are secreted by stem cell and that can be found in CM are vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), hepatocyte growth factor (HGF), platelet-derived growth factor (PDGF), bone morphogenic proteins (BMP), interleukin-6 (IL-6), macrophage colony-stimulating factor (M-CSF) and other cytokines that have been reported to be associated with hair regeneration via a variety of mechanisms[2]. VEGF, for instance, speeds up hair regeneration and augments the size of Hair Follicles and hair shafts by inducing perifollicular vascularization [3]. Dermal papilla cells (DPCs) are activated by both IGF -1/ IGF-1 binding protein-1 [4] complex and BMPs [5]. HGF, on the other hand, is a paracrine hormone that promotes follicular growth most probably by increasing the expression of B-catenin, a major player in different signalling pathways [6]. Additionally, IL-6 and M-CSF are found to play a role in hair wound-induced hair regrowth [7]. A large number of experimental studies have focused on modulating the composition and up-regulating the secretome of the stem cells, hence enhancing its therapeutic functions. 2. Stem-cell derived exosomes as vehicles of hair regenerating signals Exosomes are a sub-group of extracellular vesicles of 40-120um in size that are used as a transportation medium for cellular cargo from cell to cell [8]. Exosomes are carriers of all sorts of molecules like RNA, DNA and proteins. It has been reported that hydrophobic surface proteins on the exosomes, namely Wnt, was found to induce B-catenin activation over a distance, which is a critical signalling pathway in the regulation of hair morphogenesis and regeneration [9]. Mesenchymal stem cell-derived exosomes are one of the best candidates that have shown promise when it comes to hair regrowth, as shown by a patented experimental observation [10]. Since exosomes are involved in paracrine signalling, it is now evident that regulatory functions of DPCs in hair follicle regeneration can be exploited by DPCs derived exosomal vehicles [11]. References: 1. Kim, H.O., Choi, S.M., Kim, H.S., 2013. Mesenchymal stem cell-derived secretome and microvesicles as cell-free therapeutics for neurodegenerative disorders. 2. Kruglikov, I.L., Scherer, P.E., 2016. Dermal adipocytes and hair cycling: Is spatial heterogeneity a characteristic feature of the dermal adipose tissue depot? Exp. Dermatol. 25, 258–262 https://doi.org/10.1111/exd.12941 3. Yano, K., Brown, L.F., Detmar, M., 2001. Control of hair growth and follicle size by VEGF-mediated angiogenesis. J. Clin. Invest. 107, 409–417. https://doi.org/10.1172/JCI11317 4. Bak, D.H., Choi, M.J., Kim, S.R., Lee, B.C., Kim, J.M., Jeon, E.S., Oh, W., Lim, E.S., Park, B.C., Kim, M.J., Na, J., Kim, B.J., 2018. Human umbilical cord blood mesenchymal stem cells engineered to overexpress growth factors accelerate outcomes in hair growth. Korean J. Physiol. Pharmacol. 22, 555–566. 471 https://doi.org/10.4196/kjpp.2018.22.5.555 5. Rendl, M., Polak, L., Fuchs, E., 2008. BMP signaling in dermal papilla cells is required for their hair follicle-inductive properties. Genes Dev. 22, 543–557. https://doi.org/10.1101/gad.1614408 6. Qi, Y., Li, M., Xu, L., Chang, Z., Shu, X., Zhou, L., 2016. Therapeutic role of human hepatocyte growth factor (HGF) in treating hair loss. PeerJ 4, e2624. https://doi.org/10.7717/peerj.2624 7. Talavera-Adame, D., Newman, D., Newman, N., 2017. Conventional and novel stem cell based therapies for androgenic alopecia. Stem Cells Cloning Adv. Appl. 10, 11–19. https://doi.org/10.2147/SCCAA.S138150 8. Jiang, X.C., Gao, J.Q., 2017. Exosomes as novel bio-carriers for gene and drug 640 delivery. Int. J. Pharm., 167–175. https://doi.org/10.1016/j.ijpharm.2017.02.038 9. Dey-Rao, R., Sinha, A.A., 2017. A genomic approach to susceptibility and pathogenesis leads to identifying potential novel therapeutic targets in 531 androgenetic alopecia. Genomics 109, 165–176. https://doi.org/10.1016/j.ygeno.2017.02.005 10. Levi, S.K.L., Yeo, M.S.W., Chen, T.S., Lai, R.C., 2013. Use of exosomes to promote or enhance hair growth. US20130209528A1 11. Zhou, L., Wang, H., Jing, J., Yu, L., Wu, X., Lu, Z., 2018. Regulation of hair follicle 915 development by exosomes derived from dermal papilla cells. Biochem. Biophys. 916 Res. Commun. 500, 325–332. https://doi.org/10.1016/j.bbrc.2018.04.067
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Jamila
Jamila a year ago
Exosomes/miRNA definitely have a big role in melanin production. In a recent study, researchers found that miRNA secreted by keratinocyte derived exosomes had a role in regulating melanogenesis. Specifically, miR-330-5p was produced by keratinocyte derived exosomes. The exosomes with increased expression of miR-330-5p caused an increase in miR-330-5p in melanocytes which resulted in reduced melanin production. (https://www.sciencedirect.com/science/article/pii/S0923181119300271) On the other hand, you have miR-379 which promotes pigmentation. miR‐379 is highly expressed in alpaca melanocytes which leads to increased melanogenesis and proliferation by targeting the insulin‐like growth factor 1 receptor. (https://onlinelibrary.wiley.com/doi/abs/10.1111/exd.14095) These are just examples of how miRNA can positively or negatively impact pigmentation.
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Hair repigmentation after an anti-cancer therapy

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Darko Savic
Darko Savic Feb 16, 2021
Hair repigmentation was observed as a secondary effect during anti-programmed cell death 1 and anti-programmed cell death ligand 1 therapy for the treatment of lung cancer.

This hair repigmentation manifested itself as darkening of the hair in 13 out of 14 patients and black patches between white hairs in one patient. Scroll down to the figures section here to see the before/after photos of the patients.

[1]Rivera N, Boada A, Bielsa MI, Fernández-Figueras MT, Carcereny E, Moran MT, Ferrándiz C. Hair Repigmentation During Immunotherapy Treatment With an Anti-Programmed Cell Death 1 and Anti-Programmed Cell Death Ligand 1 Agent for Lung Cancer. JAMA Dermatol. 2017 Nov 1;153(11):1162-1165. doi: 10.1001/jamadermatol.2017.2106. PMID: 28700789; PMCID: PMC5817444.

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Blocking Noradrenaline to Prevent Hair Greying

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Jamila
Jamila Aug 28, 2020
Stress can cause the loss of hair pigment by decreasing the amount of melanocyte stem cells. Recently Zhang and colleagues found that stress activates the sympathetic nervous system (SNS) and this causes a rush of noradrenaline to be released. This burst of noradrenaline depletes the melanocyte stem cells causing the hair to turn grey. Therefore, the SNS and noradrenaline have a key role in hair greying. In Zhang's study, they used guanethidine (a drug that blocks the release of noradrenaline) in mice. Guanethidine was able to prevent stress-induced hair greying in mice and the melanocyte stem cells were not depleted. [1] Blocking noradrenaline could be used as a basis to develop novel hair greying treatments. There are many licensed noradrenaline inhibitors that are currently being used, perhaps these could be repurposed one day. References 1. Zhang, Bing, et al. "Hyperactivation of sympathetic nerves drives depletion of melanocyte stem cells." Nature 577.7792 (2020): 676-681.
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Cholinesterase Inhibitors for Grey Hairs

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Jamila
Jamila Sep 18, 2020
Some Alzheimer's patients that used cholinesterase inhibitors for at least 6 months were able to reverse the greying of their hair. The cholinesterase inhibitors that were able to mediate this reversal effect were galantamine, rivastigmine, and donepezil. [1] The researchers of the publication are unsure how the cholinesterase inhibitors actually restored the hair pigment; the researchers suspect that the cholinesterase inhibitors induced melanogenesis somehow. So the exact mechanism for this process still needs to be researched. Reference 1. Chan, Luke Kar Man, et al. "Re‐pigmentation of hair after prolonged cholinesterase inhibitor therapy in a Chinese population." Australasian Journal of Dermatology (2020).
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Summary of the articles describing medications associated with gray hair repigmentation

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Darko Savic
Darko Savic Feb 16, 2021
Here is a summary of the articles describing medications associated with gray hair repigmentation (from this review). The list below is an aggregate of 133 patients with medication-induced gray hair repigmentation:


Based on the mechanisms of action for all these drugs, is there an overall "theme" that could be pursued to come up with effective hair repigmentation therapies?
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General comments

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Darko Savic
Darko Savic8 months ago
Here is a good recent review on this topic https://www.karger.com/Article/FullText/504414
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