The colour of human hair depends on the type of melanin produced by the melanocytes from the hair follicles. Specifically, the ratio between eumelanin (darker pigment) and pheomelanin (redder pigment) make possible the different types of human hair. As we age, we see how these pigments disappear while the number of grey hairs increases. But how is grey hair formed? Can grey hair be delayed? Can it be prevented?

How grey hair is formed

Changes in hair pigmentation depend on the phase of the hair cycle. This cycle consists mainly of three phases:

  • Growth phase: anagen
  • Regression phase: catagen
  • Resting phase: telogen

In the anagen phase, hair is produced and melanogenesis is active in the hair follicle. In fully pigmented hair, the hair bulb in the anagen phase is rich in pigment-producing melanocytes, but also contains melanin-free melanocytes in the peripheral epithelium. During the greying process, the pigmented melanocytes begin to be lost from the hair bulb. During the catagen phase, keratinocytes in the capillary matrix and mature melanocytes in the hair follicle undergo apoptosis, in addition to the depigmentation of the proximal hair shaft. Finally, in the telogen phase, melanocyte stem cells are required to occupy the hair bud while the immature melanocytes in the hair matrix remain undifferentiated [1].

In contrast, the bulb of white hair does not have melanocytes, which indicates that the greying process is associated with a loss of melanocytes in the hair follicle [2]. The nervous system is involved in the greying process. Stress activates the sympathetic nerves that innervate the melanocyte stem cell niche in the hair follicle, releasing noredenaline. All this produces a rapid and permanent loss of melanocyte precursor cells, ultimately resulting in grey hair [3].

Factors that favour the appearance of grey hair

Several factors can determine the appearance of grey hair. A study was carried out in Turkey, with more than 1,000 people, to determine the most determining factors in this process. Specifically, of the 1,119 participants, almost 30% had grey hair at a young age (before 20 years old), which presented a higher level of factors that cause oxidative stress, such as emotional stress, alcohol consumption and genetically predisposed diseases in both men and women [4].

Hair cycle

Oxidative stress

During melanogenesis, which occurs in the anagen phase, melanin is produced through hydroxylation and oxidation processes that increase oxidative stress in the hair follicle. Specifically, an increase in hydrogen peroxide in grey hair follicles has been quantified [5]. In addition, an exogenous increase in oxidative stress favours the depigmentation of hair follicles and the appearance of grey hair due to the apoptosis of melanocytes in the hair bulb [6].

Genetics

Early grey hair has a hereditary component. Early greying is one of the characteristics of pathologies with genetic origin such as Werner’s syndrome, which causes accelerated aging [7]. A plausible explanation for the relationship between grey hair and progeria (diseases that cause early aging) could be the shortening of telomere length.

Telomeres are the ends of chromosomes that store all our genetic information. With each cell cycle these telomeres shorten. In the case of some progerias, such as Werner syndrome, telomere length decreases more rapidly, causing genetic instability [8]. In a study carried out on mice, it was observed how those animals that lacked telomerase had a shorter telomere length and a greater number of grey hairs than control animals [9].

Nutritional deficiencies

Some cases of premature greying are reversible, this is the case of hair hypopigmentation due to nutritional deficiencies such as vitamin B12, iron, copper, or protein. In other cases, autoimmune diseases such as pernicious anaemia due to vitamin B12 deficiency can cause early greying, it is estimated that around 55% of patients with pernicious anaemia will develop grey hair before their 50th birthday [10]. Along with pernicious anaemia, hypothyroidism can also lead to an increase in grey hair and its early appearance due to a deficiency in thyroid hormones T2 and T3, which are the ones that act on the hair follicle, increasing pigmentation [11].

Use of products against grey hair

The diverse nature of grey hair makes it difficult to develop products that can delay and even stop the appearance of grey hair. In this sense, various hormones and molecules have been described that determine hair pigmentation (melanogenesis) in the hair follicle that could be the target of products against grey hair:

  • Melanogenesis stimulators: melanin-stimulating hormone, adrenocorticotropic hormone, endothelin-1, prostaglandins, fibroblast growth factor, nitric oxide, and catecholamines [12].       
  • Inhibitors of melanogenesis: sphingolipids, bone morphogenic protein 4 [13].

In addition to investigating how to delay the appearance of grey hair, various studies have been carried out to achieve hair repigmentation with various treatments.

Image from Michal Jarmoluk in Pixabay

Anti-inflammatories

Some retinoic acid receptor activators, such as acitretin or etretinate, have been associated with hair repigmentation in 2 patients with pityriasis rubra pilaris and one with psoriasis after 6–12 months of treatment [14, 15]. Similarly, 46% of psoriasis patients treated with psoralen and UV light showed complete repigmentation after 13 months of treatment [16].Finally, anti-inflammatory cytokine inhibitors, such as adalimumab or thalidomide, have also been associated with hair repigmentation in treatments ranging from 2 months to 2 years [17].

Melanogenesis stimulators

Among the melanogenesis stimulators we find mainly tyrosine kinase inhibitors, such as imatinib or erlotinib, which produce hair repigmentation in treatments of between 3 months and two years [18, 19].Similarly, some drugs used in cancer patients seem to be related to hair repigmentation, this is the case of tamoxifen and cisplatin [20, 21]. In detail, repigmentation was observed in 16% of patients between 15 and 54 years of age who received cisplatin.

Vitamins

As we have previously mentioned, vitamin deficiencies, specifically in vitamin B, can lead to the appearance of grey hair. Therefore, the supplement of B vitamins could initiate the repigmentation of the hair. This is the case of calcium pantothenate, a vitamin B5 supplement, which produced hair repigmentation in 28% of people receiving 200 mg of calcium pantothenate daily for 3 months [22]. Similarly, supplementation with 200 mg of para-aminobenzoic acid daily resulted in repigmentation of hair in all 50 study subjects after two months of treatment [23]. Para-aminobenzoic acid is used to treat skin conditions such as scleroderma or vitiligo, given its potential as a repigmenting agent.

Therefore, even though the appearance of grey hair seems inevitable as we age, dermatological research is finding solutions to delay greying and even repigment hair that has lost its colour. More research is needed to find effective solutions that reach the market.

References

  1. O’Sullivan, J., Nicu, C., Picard, M., Chéret, J., Bedogni, B., Tobin, D. J., & Paus, R. (2021). The biology of human hair greying. Biological reviews of the Cambridge Philosophical Society, 96(1), 107–128.
  2. Commo, s., Gaillard, o., & Bernard, b. a. (2004). human hair greying is linked to a specific depletion of hair follicle melanocytes affecting both the bulb and the outer root sheath. The British Journal of Dermatology, 150(3), 435–443.
  3. Zhang, b., Ma, s., Rachmin, i., He, m., Baral, p., Choi, s., Gonçalves, w. a., Shwartz, y., Fast, e. m., Su, y., Zon, l. i., Regev, a., Buenrostro, j. d., Cunha, t. m., Chiu, i. m., Fisher, d. e., & Hsu, y. c. (2020). hyperactivation of sympathetic nerves drives depletion of melanocyte stem cells. Nature, 577(7792), 676–681.
  4. Akin Belli, A., Etgu, F., Ozbas Gok, S., Kara, B., & Dogan, G. (2016). Risk Factors for Premature Hair Graying in Young Turkish Adults. Pediatric dermatology, 33(4), 438–442.
  5. Wood, J. M., Decker, H., Hartmann, H., Chavan, B., Rokos, H., Spencer, J. D., Hasse, S., Thornton, M. J., Shalbaf, M., Paus, R., & Schallreuter, K. U. (2009). Senile hair graying: H2O2-mediated oxidative stress affects human hair color by blunting methionine sulfoxide repair. FASEB journal: official publication of the Federation of American Societies for Experimental Biology, 23(7), 2065–2075.
  6. Arck, P. C., Overall, R., Spatz, K., Liezman, C., Handjiski, B., Klapp, B. F., Birch-Machin, M. A., & Peters, E. M. (2006). Towards a “free radical theory of graying”: melanocyte apoptosis in the aging human hair follicle is an indicator of oxidative stress induced tissue damage. FASEB journal: official publication of the Federation of American Societies for Experimental Biology, 20(9), 1567–1569.
  7. Oshima, J., Martin, G. M., & Hisama, F. M. (2002). Werner Syndrome. In M. P. Adam (Eds.) et. al., GeneReviews®. University of Washington, Seattle.
  8. Crabbe, L., Jauch, A., Naeger, C. M., Holtgreve-Grez, H., & Karlseder, J. (2007). Telomere dysfunction as a cause of genomic instability in Werner syndrome. Proceedings of the National Academy of Sciences of the United States of America, 104(7), 2205–2210.
  9. Blasco MA, Lee HW, Hande MP, et al. Telomere shortening and tumor formation by mouse cells lacking telomerase RNA. Cell.1997;91:25-34.
  10. Dawber R. P. (1970). Integumentary associations of pernicious anaemia. The British journal of dermatology, 82(3), 221–223.
  11. van Beek, N., Bodó, E., Kromminga, A., Gáspár, E., Meyer, K., Zmijewski, M. A., Slominski, A., Wenzel, B. E., & Paus, R. (2008). Thyroid hormones directly alter human hair follicle functions: anagen prolongation and stimulation of both hair matrix keratinocyte proliferation and hair pigmentation. The Journal of clinical endocrinology and metabolism, 93(11), 4381–4388.
  12. Tobin DJ, Paus R. Graying: gerontobiology of the hair follicle pigmentary unit. Exp Gerontol. 2001 Jan;36(1):29-54. doi: 10.1016/s0531-5565(00)00210-2. Erratum in: Exp Gerontol 2001 Mar;36(3):591-2. PMID: 11162910.
  13. Park, A. M., Khan, S., & Rawnsley, J. (2018). Hair Biology: Growth and Pigmentation. Facial plastic surgery clinics of North America, 26(4), 415–424.
  14. Ward, P. D., Miller, H. L., & Shipman, A. R. (2014). A case of repigmentation and curling of hair on acitretin therapy. Clinical and experimental dermatology, 39(1), 91–92.
  15. Vesper, J. L., & Fenske, N. A. (1996). Hair darkening and new growth associated with etretinate therapy. Journal of the American Academy of Dermatology, 34(5 Pt 1), 860.
  16. Pavithran K. (1986). Puvasol Therapy in Premature Greying of Hair. Indian journal of dermatology, venereology and leprology, 52(2), 74–75.
  17. Yale, K., Juhasz, M., & Atanaskova Mesinkovska, N. (2020). Medication-Induced Repigmentation of Gray Hair: A Systematic Review. Skin appendage disorders, 6(1), 1–10.
  18. Cheng, Y. P., Chen, H. J., & Chiu, H. C. (2014). Erlotinib-induced hair repigmentation. International journal of dermatology, 53(1), e55–e57.
  19. Alexandrescu, D. T., Kauffman, C. L., & Dasanu, C. A. (2009). Persistent hair growth during treatment with the EGFR inhibitor erlotinib. Dermatology online journal, 15(3), 4.
  20. Hampson, J. P., Donnelly, A., Lewis-Jones, M. S., & Pye, J. K. (1995). Tamoxifen-induced hair colour change. The British journal of dermatology, 132(3), 483–484.
  21. Robinson, A., & Jones, W. (1989). Changes in scalp hair after cancer chemotherapy. European journal of cancer & clinical oncology, 25(1), 155–156.
  22. Pasricha J. S. (1986). Effect of Grey Hair Evulsion on the Response to Calcium Pantothenate in Premature Grey Hairs. Indian journal of dermatology, venereology and leprology, 52(2), 77–80.
  23. Sieve B. F. (1941). Clinical achromotrichia. Science (New York, N.Y.), 94(2437), 257–258.

Cover image by Andrea Piacquadio in Pexels

 

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