Age-associated thin hair displays molecular, structural and mechanical characteristic changes.

Hair thinning occurs during normal chronological aging in women and in men leading to an increased level of thinner hair shafts alongside original thicker shafts. However, the characteristics of age-associated thin hairs remain largely unknown. Here we analyzed these characteristics by comparing at multiscale thin and thick hairs originated from Caucasian women older than 50 years. We observed that the cortex of thick hair contains many K35(+)/K38(-) keratinocytes that decrease in number with decreasing hair diameter. Accordingly, X-ray diffraction revealed differences supporting that thin and thick hairs are different with regards to the nature of the intermediate filaments making up their cortices. In addition, we observed a direct correlation between hair ellipticity and diameter with thin hairs having an unexpected round shape compared to the elliptic shape of thick hairs. We also observed fewer cuticle layers and a reduced frequency of a medullae in thin hairs. Regarding mechanical properties, thin hairs exhibited a surprising increased rigidity, a decrease of the viscosity and a decrease of the water diffusion coefficient. Hence, aged-associated thin hairs exhibit numerous modifications likely due to changes of hair differentiation program as evidenced by the modulations in the expression of hair keratins and keratin-associated proteins and by the X-ray diffraction specters. Hence, hair thinning with age does not consist simply of the production of a smaller hair. It is rather a more profound process likely relying on the implementation of an "aged hair program" that takes place within the hair follicle.

Acid hydrolysis reveals a low but constant level of pheomelanin in human black to brown hair.

We previously reported a constant ratio of the benzothiazole pheomelanin marker thiazole-2,4,5-tricarboxylic acid (TTCA) to the eumelanin marker pyrrole-2,3,5-tricarboxylic acid (PTCA) in eumelanic, black human hair. A constant level (20%-25%) of benzothiazole-type pheomelanin was recently demonstrated in human skin with varying concentrations of melanin. Therefore, in this study, we aimed to investigate the origin of pheomelanin markers in black to brown human hair by developing a method to remove protein components from hair by heating with 6 M HCl at 110°C for 16 hr. For comparison, synthetic melanins were prepared by oxidizing mixtures of varying ratios of dopa and cysteine with tyrosinase. Hair melanins and synthetic melanins were subjected to acid hydrolysis followed by alkaline H2 O2 oxidation. The results show that the hydrolysis leads to decarboxylation of the 5,6-di-hydroxyindole-2-carboxylic acid moiety in eumelanin and the benzothiazole moiety in pheomelanin and that eumelanic human hair contains 11%-17% benzothiazole-type pheomelanin.

Melanins and melanogenesis: from pigment cells to human health and technological applications.

During the past decade, melanins and melanogenesis have attracted growing interest for a broad range of biomedical and technological applications. The burst of polydopamine-based multifunctional coatings in materials science is just one example, and the list may be expanded to include melanin thin films for organic electronics and bioelectronics, drug delivery systems, functional nanoparticles and biointerfaces, sunscreens, environmental remediation devices. Despite considerable advances, applied research on melanins and melanogenesis is still far from being mature. A closer intersectoral interaction between research centers is essential to raise the interests and increase the awareness of the biomedical, biomaterials science and hi-tech sectors of the manifold opportunities offered by pigment cells and related metabolic pathways. Starting from a survey of biological roles and functions, the present review aims at providing an interdisciplinary perspective of melanin pigments and related pathway with a view to showing how it is possible to translate current knowledge about physical and chemical properties and control mechanisms into new bioinspired solutions for biomedical, dermocosmetic, and technological applications.

Neutral pH and copper ions promote eumelanogenesis after the dopachrome stage.

The diversity of pigmentation in the skin, hair, and eyes of humans has been largely attributed to the diversity of pH in melanosomes with acidic pH being proposed to suppress melanin production. Tyrosinase has an optimum pH of 7.4 and its activity is suppressed greatly at lower pH values. The first step of eumelanogenesis is the oxidation of tyrosine to dopachrome (DC) via dopaquinone. However, how eumelanogenesis is controlled by pH beyond this stage is not known. In this study, we examined the effects of pH (5.3-7.3) on the conversion of DC to 5,6-dihydroxyindole (DHI) and 5,6-dihydroxyindole-2-carboxylic acid (DHICA) and the subsequent oxidation of DHI and DHICA to form eumelanin. The effects of Cu(2+) ions on those reactions were also compared. The results indicate that an acidic pH greatly suppresses the late stages of eumelanogenesis and that Cu(2+) ions accelerate the conversion of DC to DHICA and its subsequent oxidation.

TRP-2 specifically decreases WM35 cell sensitivity to oxidative stress.

TRP-2 (dopachrome tautomerase) is a melanogenic enzyme whose expression was recently reported to modulate melanocyte response to different cytotoxic events. Here we studied a possible role of TRP-2 in the oxidative stress response in the amelanotic WM35 melanoma cell line. Cell viability assays showed that TRP-2 overexpression in WM35 cells reduced their sensitivity to oxidative stress. Comet assays linked TRP-2 expression to DNA damage protection, and high-performance liquid chromotography-tandem mass spectrometry experiments showed an increase in intracellular glutathione in TRP-2-overexpressing cells. These effects were specifically reversed when TRP-2 was silenced by RNA interference. Nevertheless, these properties appeared to depend on a particular cell environment because expression of TRP-2 failed to rescue HEK epithelial cells exposed to similar treatments.

Absence of TRP-2 in melanogenic melanocytes of human hair.

Skin and hair colour mostly depend on the activity of melanogenic melanocytes. Numerous proteins involved in melanocyte function have been identified including pMel-17, Mitf-M, Sox10, tyrosinase, tyrosinase related proteins-1 (TRP-1) and -2 (TRP-2). In the hair, melanogenic activity occurs only during the anagen phase of the hair cycle. In order to evaluate the implications of some known melanogenic proteins in human hair pigmentation, we performed immunohistochemical studies to reveal the expression of pMel-17, Mitf-M, tyrosinase, TRP-1 and TRP-2 in active bulb melanocytes of eumelanic brown and black anagen hairs of different ethnic origins, e.g. brown Caucasian, black Asian and African hairs. The labelling was compared with that observed in Caucasian and African scalp epidermis (interfollicular epidermis) melanocytes. We found that while pMel-17, TRP-1 and TRP-2 were expressed in epidermal melanocytes irrespective of ethnic origin and melanin content of the scalp epidermis, Mitf-M and tyrosinase expression were clearly evidenced only in pigmented epidermis, e.g. African scalps. Regarding human hair, pMel-17, Mitf-M, tyrosinase and TRP-1 were detected in a similar manner in active bulb melanocytes of brown and black hairs. In contrast and unexpectedly, TRP-2 could not be detected in hair bulb melanocytes, whatever the hair colour and ethnic origin. The lack of TRP-2 was further confirmed by western blot analyses. Reverse transcriptase-polymerase chain reaction (RT-PCR) performed on hair bulb mRNA demonstrated that Mitf-M, tyrosinase and TRP-1 amplimer signals were easily detected, whereas the TRP-2 amplimer signal was barely detectable. Furthermore Sox10 was not detected in hair bulb. Altogether our results suggest that the absence of detectable level of TRP-2 is due to transcriptional control in active melanocytes of human eumelanic hair bulbs. According to the absence of TRP-2 in melanin-producing melanocytes of brown and black hair bulbs, one must consider that eumelanogenesis as well as brown and black colour do not require TRP-2 expression in human hair.