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About greying hair

INTRODUCTION

Hair has been the subject of myths, treatments and, even, fantasies. Its length, colour, shine and appearance always influence people’s perceptions of us, whether for good or bad. Hair colour is intrinsically linked to our individual identity, and is often linked to social norms, as well as current fashion and trends.

Greying hair is inevitable, it develops with age, and is a universal problem unrelated to gender. However, for almost everyone, it is viewed as a tangible sign of ageing and one that can seriously affect self-esteem. In general, people start going grey between the ages of 25 and 35, depending on the population in question, but this can vary widely between individuals. For the majority, premature greying (<20 years) is caused by associated diseases. However, it can be associated with factors like stress, diet, medications, such as chloroquine, and smoking (ZAYED et al., 2013).

The term “grey hair” refers to a head of hair that contains a mixture of hairs with normal pigmentation and hair with deficient or no pigmentation. The appearance of grey hairs varies in intensity and frequency according to geographical area, and, therefore, the ethnic origin of the population under study (PANHARD et al., 2012). For example, among 45–64-year-olds, intensity varies from 15 % to 37 %. The majority of white hairs do not contain melanin. The amount of melanin produced by follicular melanocytes starts to decrease, and eventually stops completely.

While very rare cases of spontaneous repigmentation have been reported (PANDHI et al., 2013), hair colour treatments have been the most widely-used solution for thousands of years. Hair colour treatments provide instant results, but they are not without risks, such as irritations or sensitisation, or worse. Hair colour treatments are most popular among women in Western countries, but they are also widely used by men in the East.

Another solution is to stimulate melanin synthesis by melanocytes in the hair and to activate the key enzyme in melanogenesis, tyrosinase. This requires stimulation of the pigmentation pathways, in particular, by boosting certain intermediates such as MITF, TYRP1 and CREB, which are highly involved in this process. It also is essential to promote communication between follicular melanocytes and the keratinocytes that produce hair, through the dendrites. It facilitates melanin transfer from melanocytes to keratinocytes.

The process of greying can also be curbed by providing antioxidant protection for melanocytes. The intense activity of melanocytes throughout the hair growth cycle (3 to 5 years), produces harmful Reactive Oxygen Species (ROS), like hydrogen peroxide. These radicals damage cells and affect pigment function over time. Stimulating catalase and reduced glutathione helps control these radicals.

GENERAL BACKGROUND

The symbolism of hair

Our hair is an essential part of our personality. Since time began, whether man or woman, the length, colour, shine and appearance of our hair has influenced other people’s perceptions of us.

Hair plays an important role in mythology. It captures our imagination because of its secondary sexual nature and the unconscious attraction it can arouse in others. In many cultures, whether Indian, Egyptian, Greek or Germanic, people had to keep their hair in pristine condition because it was a sign of virility, strength, royalty or beauty. It was a marker of social and hierarchical status. All over the world, the way in which hair is styled and coloured, for both men and women, whether in Babylon, China, Egypt, or Ancient Rome, is closely linked to social and civil status.

Hair colour is one of the most visible human characteristics. Hair can be black, brown, blonde or red, with a wide variety of shades in between. Although completely white hair is often associated with great wisdom, men and women have always sought out ways to colour their grey hair because of its ageing effect.

A brief history of colour treatments for grey hair

The natural colour of our hair is linked to the presence of two types of melanin, which are also responsible for skin and eye colour. These organs produce eumelanin, which is brown or black, and pheomelanin, which is red or yellow. The balance between these two pigments determines all possible shades. However, like all organs, hair ages, which reduces pigmentation.

From as early as Ancient Egypt, recipes for scalp conditioning treatments as well as colouring treatments can be found in the Ebers Papyrus, using an ointment made from boiled blood taken from the base of the horns of a black bull. The iconic Pharaoh, Ramses II, used to dye his grey hair with henna and his contemporaries coloured their black hair with indigo. Pliny the Elder reported that the Romans, depending on which shade they wanted, coloured their hair with henna, saffron or a marinade of leeches in red wine. In the De Ornato Mulierum treatise from the Middle Ages, there is a recipe made from a mysteriously headless and tailless lizard, designed to hide grey hair, a formula which was also recorded by the famous Nostradamus in his treatise of 1550. Nowadays, artificial and natural hair dyes are available on the market and both have advantages and disadvantages. Artificial hair dyes are long-lasting and often contain chemical bonding agents (hydrogen peroxide or oxygenated water, ethanolamine, paraphenylenediamine, etc.) which can be sensitising. Natural hair dyes made of henna, indigo or katam, last for a relatively modest amount of time.

The evolutionary role of hair and melanin

About 90 % of the world’s population has black hair, which is very rich in eumelanin. Only a small proportion of people have more varied hair colours, a characteristic that emerged late on in the migration to the cold regions of Europe. Three characteristics, the extraordinary length of hair, as well as its thickness and richness in melanin, were retained through evolution thanks to their selective benefits for humans. These three characteristics make humans an exception among primates.

Evolutionary researchers claim that the melanin in the hair of our distant ancestors helped them to better survive in their environment, which, paradoxically, was naturally polluted by heavy metals.

Eumelanin has a high affinity with metals and toxins which enables toxins in food or the environment to be effectively removed from our blood, using little energy. These products, thus rendered harmless, are stored outside the body in the inert structure of the hair. Having darker hair would therefore be an ingenious and safe way to increase the body’s purifying capacities (TOBIN, 2008; WOOD et al., 1999).

Each one of our 90,000 to 130,000 hair follicles has its own vascular network, in the dermal capillary, which also acts as an exchange surface with the body. In addition, humans have a significant amount of body, eyelash and eyebrow hair (almost 2 million hairs). The fact that the presence of drugs and doping agents can be detected in the hair of athletes demonstrates this little-known property.

Another property of eumelanin is its capacity to modulate the balance of calcium, an ion essential to cell homeostasis and, more specifically, to the maturity of keratinocytes, cells which play an important role in hair growth. Calcium is also involved in pigmentation and the transport of melanosomes (Figure 1).

Figure 1. Melanin synthesis in melanosomes, transfer to epidermal keratinocytes; according to WIRIYASERMKUL et al., 2020.

Figure 2 Melanin synthesis stages

 

In addition, eumelanin is a detoxifier of cytotoxic free radicals. In particular, it neutralises the superoxide anion (O2°-) which is generated by the oxidative stress associated with pollutants or sun exposure. This anion O2°- enables the production of hydrogen peroxide, also known as oxygenated water (H2O2), in cells. However, O2°- is required for melanin production, so that the enzyme tyrosinase can convert L-Tyrosine to Dopaquinone (Figure 2). The cell thus finds a useful polymer for controlling this anion (WOOD et al., 1999).

Eumelanin, due to its high concentration in hair, blocks the damaging effects of UV and infrared radiation on the hair fibre. Loss of hair pigmentation (scientifically known as canities) caused by ageing results in weakened hair, and permanent dyes and colouring agents subsequently have less hold, an adverse effect that is well known to hairdressers (WOOD et al., 1999).


FREQUENCY AND INTENSITY OF GREY HAIR

The term grey hair indicates that the head of hair consists of hair with natural, darker and stronger pigmentation, hair in an intermediate state, with reduced melanin intensity, and hair that appears completely white. With age, the first group decreases in favour of the other two. The hair’s white appearance is an optical effect caused by the reflection of incident light, which masks the very pale-yellow colour of keratin (PANDHI et al., 2013).

Greying hair due to age is a universal issue that is common among both men and women.

Cases of very premature greying are often associated with autoimmune diseases, including vitiligo and the rare disorder known as Werner’s syndrome. They can also be related to vitamin deficiencies or to the use of molecules such as chloroquine (DI GIACOMO et al., 2009). However, some non-pathological cases have been reported.

The average age for starting to go grey in the Caucasian population is 34±9.6 years, and 43.9±10.3 years in the African population. With regard to premature greying, there are also differences between major ethnic groups. Natural greying is considered premature in Caucasian adults if it occurs before the age of 20, before the age of 25 for Asian populations and before the age of 30 for African populations (ANGGRAINI et al., 2019; KUMAR et al., 2018; TOBIN et al., 2001).

Our hair goes through a greying phase before turning completely white. White hair does not contain melanin because it is no longer being produced by the follicular melanocytes.

The proportion of white hair increases progressively with age. The 50-50-50 rule states that 50 % of people over 50 have at least 50 % grey hair (JO et al., 2018). A number of authors have published different values with regard to the percentage of grey hair. This is because there is no standardised scoring method (SINGAL et al., 2016). The 50-50-50 rule was contradicted by a study which produced a different percentage for the population (PANHARD et al., 2012).

This study, involving 4,192 male and female volunteers, demonstrated that by the age of 45, 57 % of people have grey hair, with an average intensity of 15 %. By age 50, 6-23 % of the world’s population has 50 % grey hair. Over the age of 60, 91 % of the world’s population has grey hair, with an average intensity of 40 %.

table1

Table 1 shows the frequency and intensity of grey hair by geographical area at comparable ages. It should be noted that Sub-Saharan and African-American populations have the lowest frequencies of grey hair of all the populations studied. Conversely, North Africans (87 %), Mexicans (89 %), Caucasian-Americans (85 %), Russians (84 %), Polish (82 %), French (93 %) and Lebanese (91 %) are ranked among the highest. Asian populations are ranked at both ends of the spectrum, with the Japanese having the lowest frequency, while Koreans and Chinese have the highest. Indians are ranked at similar levels to European populations.

In men, hair is more likely to go grey around the temples, followed by the top of the head. In women, the temples and top of the head tend to go grey around the same time and with the same intensity.

Greying hair almost always has a negative impact on self-confidence and often affects relationships with others. As a rule, the solution for women is to colour their hair, but this is much less true of men.

We will provide a brief overview of the hair growth cycle before outlining pigmentation modulations, as these two phenomena are very closely linked in nature.

Hair growth

Hair (Figure 3) is one of the most highly proliferative organs of the body. It grows approximately 1 cm per month. Unlike in mice, the growth of each human hair is independent of the others. The life and death of hair is a drama which plays out in three acts: A.C.T.

Active growth of the hair and the process of melanisation by melanocytes in the bulb only occur during the growth phase of the hair, known as the anagen phase (A). On average, this phase lasts 2 to 5 years, but can continue for up to 10 years in extreme cases (TOBIN, 2008). 85-90 % of hair is usually in the anagen phase.

Before this phase, the root sheath is empty (Figure 4). The base of the old hair is formed by a structure known as the dermal papilla (DP), which is rich in cells similar to fibroblasts. The DP is located in contact with the bulbous part of the sheath called the bulge, where the hair stem cells (which are melanocytic and keratinocytic) are found. The proximity of the dermal layer and these stem cells results in a profound change to the synthesis of these cells, which are usually non-proliferative, and causes the new follicle to enter the anagen phase.

With regard to hair fibre growth, the new set of dermal papilla and keratinocyte progenitor cells form a highly proliferative structure that elongates the sheath and moves it away from the bulge (Figure 4-(2)). During this phase, several cell types appear, outer root sheath cells (Figure 4), inner sheath cells and the associated cells which play a role in their maturation (MESLER et al., 2017). Subsequently, the structure enlarges, encompassing the dermal papilla. It progresses into the dermis and reaches its final position deep within the skin. At this point, fibre manufacture begins with the intense production of keratins and keratinocytes which then form the outer hair cuticles and cortex.

Figure 3. Hair follicle structure.

Figure 4. Hair growth cycle and melanisation, according to LIEN, 2020

At the end of the anagen phase, the follicle enters a regression phase called the catagen phase (C) and synthesis stops. The fibre no longer grows, due to the lack of supply to the DP from the blood vessels (Figure 3-(3)). This phase only lasts only a few weeks and affects about 2 to 3 % of all hair. The follicle gradually involutes. Keratinocyte cells and melanocytes gradually disappear. The bulb collapses on itself but retains the dermal papilla.

Next, the papilla begins to move towards the bulge, this is known as the telogen phase (T) which precedes a new anagen phase. 8 to 10 % of the entire head of hair is in the telogen phase. Hair remains in this phase for about 6 to 7 months in young people, but for longer as people age (TOBIN et al., 2001).


Hair melanisation

Melanin is produced in the same way whether in the epidermis or the hair follicles. In all cases, L-Tyrosine is the initial substrate for the enzyme tyrosinase (TYR, Figure 2) whose activity produces Dopaquinone. This molecule is the starting point for the two types of melanin: pheomelanin and eumelanin (Figure 2). Tyrosinase activity is one of the preferred targets of pigmentation-reducing products on the market, such as arbutin, which competes with tyrosine at the same site and therefore inhibits melanin production. Conversely, an increase in its general activity promotes better pigmentation thanks to the resulting increase in melanin production (TOBIN, 2008).

Eumelanin is synthesised following several transformations due to the action of other enzymes such as TYRP1 and TYRP2 (Figure 2). Pheomelanin takes another route and uses the sulphur amino acid L-Cysteine.

This synthesis, which decreases and then stops altogether at the end of the hair growth phase, is accompanied by a retraction of the dendrites. Tyrosinase activity can no longer be detected. In the catagen phase, the melanocytes do not survive this phase (TOBIN, 2008).

With age, grey and white hair (beard hair included) appears to grow more rapidly than hair that is still pigmented. This indicates that melanin plays an inhibitive role in the proliferation of fibre-forming keratinocytes (NAGL and ARCK quoted in TOBIN, 2008; FERNANDEZ-FLORES et al., 2019). Controversially, JO (2018) suggests that one way to moderate greying hair would be to reduce the hair growth rate of an individual.

Figure 5. Pigmented human melanocytes with dendrites and melanosomes. Sederma photo

Causes of greying hair

Greying hair is closely linked to chronic ageing. It quickly becomes highly visible, unlike the ageing process of other organs. The actual causes of greying hair are still up for debate because of the difficulties still involved in studying this complex organ. It is often cited that a genetic element must be at play, but with additional factors influencing the speed and intensity with which it appears. Moreover, and this is a little-known fact, although melanin production is highly beneficial for protecting our skin from the sun, it is not without risk or consequences for the cell that produces it (TOBIN, 2008).

SAXENA et al., 2020 demonstrated that premature greying was accompanied by an increase in the by-products of lipid oxidation in the blood and a decrease in reduced glutathione (rGSH), a powerful natural antioxidant.

Pollution, stress, diet, smoking, obesity and microinflammatory stress are likely factors in accelerating the premature onset of canities (FERNANDEZ-FLORES et al., 2019; ZAYED et al., 2013). This additional stress also damages the keratinocytes found close to melanocytes and their production of the soluble factors involved in melanogenesis. Sunlight, on the other hand, does not seem to activate the greying process, either in terms of time (premature onset) or intensity.

There is a certain consensus that greying hair is linked to a strong decrease in active melanocytes, to varying degrees, in the bulb of grey hair due to the effects of ageing and oxidative stress. This leads to a lower rate of melanin and melanosome production, as well as a reduction in dendrite size and a decrease in the transfer of dendrites to the keratinocytes. There is also less tyrosinase activity and melanocytes demonstrate increased cytoplasmic vacuolisation, indicating oxidative stress. In white hair, no melanocytes are found in the bulb. They are unable to migrate during a new cycle (FERNANDEZ-FLORES et al., 2019).

Follicular melanocytes have intense synthetic activity. These cells never stop working, as hair grows continuously by 0.3 mm per day over many years. And yet, melanogenesis produces many radical and oxidising species including H2O2 (hydrogen peroxide). Over many months and years, this causes cumulative oxidative damage to melanocytes. Thus, grey hair follicles are significantly associated with greater mitochondrial DNA damage and increased apoptosis.

Mice that are deficient in the Bcl-2 protein, which protects cells from death by apoptosis, demonstrate rapid greying. Bcl-2 can also have an antioxidant and protective effect on melanocytes (SAXENA et al., 2020).

With age, the cell’s other antioxidant defences are diminished, in particular, catalase production which is responsible for the detoxification of H2O2 into oxygen and water (KAUSER et al., 2007). This has cytotoxic implications for the follicle. Within the skin, this process causes areas of skin to appear that can sometimes be totally discoloured, a disease called vitiligo.

The Ethne and Sederma concept for combating grey hair

Serum Ethne contains SILVERFREE™, a cosmetic active ingredient developed by SEDERMA, using the technology of perfect characterised peptides. SEDERMA is the global expert in this technology. 

This peptide was found after testing several dozen peptide sequences on normal human melanocytes. It complements the wide range of peptides that SEDERMA already provides to the global cosmetic industry with activities targeting the dermal and epidermal layers of the skin (e.g. peptides from the Matrixyl® and Crystalide® family). SILVERFREE acts on another skin compartment: the hair follicle. This peptide stimulates melanin synthesis in the melanocytes, the cells responsible for hair colour. SILVERFREE stimulates melanocytes’ defence mechanisms against oxidative stress and the resulting cellular damage. It also promotes the transfer of melanin into the keratinocytes, the cells at the origin of the hair fibre.

SILVERFREE actively and significantly reduces grey hair, with long-term effects.

pPP peptide

Figure 6. Formula of the pPP peptide.

BIBLIOGRAPHY

Anggraini D.R., Feriyawati L., Hidayat H. and Wanhyuni A.S. (2019) “Risk factors associated with premature hair greying of young adult.” Open Access Maced. J. Med. Sci., 7, 3762-3764.

Di Giacomo T.B., Valente N.Y.S. and Nico M.M.S. (2009) “Chloroquine – induced hair depigmentation”. Lupus, 18, 264-266.

Fernandez-Flores A., Saed-Lima M. and Cassarino D.S. (2019) “Histopathology of aging of the hair follicle.” J. Cutan. Pathol., 46, 508-519.

Jo S.K., Lee Y., Kim C.D., Lee J-H. and Lee Y.H. (2018) “Three streams for the mechanism of hair graying.” Ann. Dermatol., 30, 397-401.

Kauser S., Westgate G., Green M. and Tobin D.J. (2007) “Age-associated down regulation of catalase in human scalp hair follicle melanocytes.” Pigment Cell Res., 20, 432.

Kumar A.B., Shamim H. and Nagaraju U. (2018) “Premature graying of hair: review with updates.” Int. J. Trichology, 10, 198-203.

Lien W.-H. (2020) Signaling cros-talk in skin stem cells, Duve Institute, Bruxelles.

Mesler A.L., Veniaminova N.A., Lull M.V. and Wong S.Y. (2017) “Hair follicle differentiation is orchestrated by distinct early and late matrix progenitors.” Cell Rep., 19, 809-821.

Pandhi D. and Khanna D. (2013) “Premature graying of hair.” Indian J. Dermatol. Vener. Leprol., 79, 641-653.

Panhard S., Lozano I. and Loussouarn G. (2012) “Greying of the human hair: a worldwide survey, revisiting the ‘50’ rule of thumb.” Br. J. Dermatol., 167, 865-873.

Pillaiyar T., Manickam M. and Jung S-H. (2017) “Recent development of signaling pathways inhibitors of melanogenesis.” Cell. Signal., 40, 99-115.

Saxena S., Gautam R.K., Gupta A. and Chitkara A. (2020) “Evaluation of systemic oxidative stress in patients with premature canities and correlation of severity of hair graying with the degree of redox imbalance.” Int. J. Trichology, 12, 16-23.

Singal A., Daulatabad D. and Grover C. (2016) “Graying severity score: a useful tool for evaluation of premature canities.” Ind. Dermatol. Online, 7, 164-167.

Slominski A., Wortsman J., Plonka P.M., Schallreuter K.U., Paus R. and Tobin D. J. (2005) “Hair follicle pigmentation.” J. Invest. Dermatol., 124, 13-21.

Tobin D.J. and Paus R. (2001) “Graying: Gerontobiology of the hair follicle pigmentary unit.” Exp. Gerontol., 36, 29-54.g

Tobin D.J. (2008) “Human hair pigmentation – biological aspects.” Int. J. Cosmet. Sci., 30, 233-257.

Wiriyasermkul P., Moriyama S. and Nagamori S. (2020) “Membrane transport proteins in melanosomes: regulation of ions for pigmentation.” BBBA Biomembr., In Press.

Wood J.M., Jimbow K., Boissy R.E., Slominski A. Plonka P.M., Slawinski J., Wortsman J. and Tosk J. (1999) “What’s the use of generating melanin?” Exp. Dermatol., 8, 153-164.

Xiao L., Zhang R-Z and Zhu W-Y. (2019) “The distribution of melanocytes and the degradation of melanosomes in fetal hair follicles.” Micron, 119, 109-116.

Zayed A.A., Shahait A.D., Ayoub M.N. and Yousef A-M. (2013) “Smokers’ hair: does smoking cause premature hair graying.” Ind. Derm. Online J., 4, 90-92.