Age-related hair pigment loss

YesHumans are social animals that communicate disproportionately via potent genetic signals imbued in the skin and hair, including racial, ethnic, health, gender, and age status. For the vast majority of us, age-related hair pigment loss becomes the inescapable signal of our disappearing youth. The hair follicle (HF) pigmentary unit is a wonderful tissue for studying mechanisms generally regulating aging, often before this becomes evident elsewhere in the body. Given that follicular melanocytes (unlike those in the epidermis) are regulated by the hair growth cycle, this cycle is likely to impact the process of aging in the HF pigmentary unit. The formal identification of melanocyte stem cells in the mouse skin has spurred a flurry of reports on the potential involvement of melanocyte stem cell depletion in hair graying (i.e., canities). Caution is recommended, however, against simple extrapolation of murine data to humans. Regardless, hair graying in both species is likely to involve an age-related imbalance in the tissue's oxidative stress handling that will impact not only melanogenesis but also melanocyte stem cell and melanocyte homeostasis and survival. There is some emerging evidence that the HF pigmentary unit may have regenerative potential, even after it has begun to produce white hair fibers. It may therefore be feasible to develop strategies to modulate some aging-associated changes to maintain melanin production for longer

Demographic characteristics and association of serum Vitamin B12, ferritin and thyroid function with premature canities in Indian patients from an urban skin clinic of North India: A retrospective analysis of 71 cases

yesBackground: The incidence of self-reported premature hair graying (PHG) seems to be on the rise. PHG has a profound impact on the patient's quality of life. It remains an incompletely understood etiology with limited and modest treatment options. Aim: The evaluation of the demographic and clinical profile of patients with premature canities, and exploration of the association of this entity with certain systemic disorders suspected to be related to its etiology. Methods: Seventy-one cases of premature canities (onset noticed by patients before 25 years of age) presenting to an urban skin clinic in Gurugram, India, between September 2012 and September 2015 with this complaint were retrospectively analyzed. The patient records were retrieved that provided details of the onset, duration and pattern of involvement, history, and examination findings (scalp, cutis, and general physical). Since all these patients had been screened for anemia, thyroid disorder, fasting blood glucose, and Vitamin B12 levels at the time of presentation, these parameters were also available for analysis. Results: The mean age at onset of graying was 10.2 ± 3.6 years (range: 5–19 years), with an almost equal gender distribution. The earliest age of onset recorded was 5 years. A positive family history of PHG (at least one of the biological parents or siblings) was obtained in 64 (90.1%) of the cases. The temporal regions of the scalp (35.2%) were most commonly involved followed by the frontal region (18.3%). Hypovitaminosis B12 and hypothyroidism showed significant association with the disorder, whereas anemia, serum ferritin, and fasting blood glucose did not. Conclusion: The age of onset of hair graying can be as low as 5 years. Temporal and frontal areas are the most commonly involved sites. A strong family history, Vitamin B12 deficiency, and hypothyroidism are strongly associated with PHG. Larger case–control studies are mandated for discerning the correlation of these and other risk factors with PHG

Hair Pigmentation: A Research Update

Hair is a uniquely mammalian trait with important functions, most easily appreciated in furred mammals. Our skin and hair color contribute very significantly to our overall visual appearance by highlighting striking variations between human sub-groups. Although melanins, hemoglobins, and carotenoids define the color perceived at the skin surface, our hair color relies only on the presence or absence of different melanins. The hair shaft's physical aspects provide only minor color modification. Various selective evolutionary pressures have determined that within the context of our specific ethnic backgrounds a bewildering array of natural shades are seen; ranging from yellows, reds, and browns to black and that harbinger of lost youth, gray/white hair. Skin/hair follicle melanins are formed in cytoplasmic organelles called melano-somes produced by neural crest-derived pigment cells called melano-cytes and are the product of a complex, phylogenetically ancient, biochemical pathway called melano-genesis. The following provides a review of research presented at the 4th Intercontinental Meeting of Hair Research Societies 2004 and so is not intended to represent a fully comprehensive overview of the subject—for that readers are directed to key references

Systematic associations between germ-line mutations and human cancers

YesThe revolution in Big Data has opened the gate for new research challenges in biomedical science. The aim of this study was to investigate whether germ-line gene mutations are a significant factor in 29 major primary human cancers. Using data obtained from multiple biological databases, we identified 424 genes from 8879 cancer mutation records. By integrating these gene mutation records a human cancer map was constructed from which several key results were obtained. These include the observations that missense/nonsense and regulatory mutations might play central role in connecting cancers/genes, and tend to be distributed in all chromosomes. This suggests that, of all mutation classes missense/nonsense and regulatory mutation classes are over-expressed in human genome and so are likely to have a significant impact on human cancer aetiology and pathomechanism. This offers new insights into how the distribution and interconnections of gene mutations influence the development of cancers

The Fate of Hair Follicle Melanocytes During the Hair Growth Cycle

The fate of the follicular pigmentary unit during the hair growth cycle has long been one of the great enigmas of both hair follicle and pigment cell biology. Although melanocytes are distributed in several different compartments of the anagen hair follicle, melanogenically active cells are located only in the hair bulb, where they are directly involved in hair shaft pigmentation. These pigment cells are readily detectable only when they become melanogenically active during anagen III of the hair growth cycle. Thus, their status during hair follicle regression (catagen), when melanogenesis is switched off, until they re-appear again as pigment-producing cells in the anagen III hair follicle, has remained poorly defined. Historically, it has been proposed that hair bulb melanocytes adopt a self-perpetuating, catagen-resistant strategy of de-differentiation during hair follicle regression and re-differentiation upon entry into a new anagen phase; however, this explanation remains problematic in the absence of evidence for de-differentiation/re-differentiation plasticity in most nonmalignant cell systems

Melanin fate in the human epidermis: a re-assessment of how best to detect and analyze histologically

YesMelanin is the predominant pigment responsible for skin colour, and is synthesized by the melanocyte in the basal layer of the epidermis and then transferred to surrounding keratinocytes. Despite its optical properties, melanin is barely detectable in unstained sections of human skin. However, identification and localization of melanin is of importance for the study of skin pigmentation in health and disease. Current methods for the histologic quantification of melanin are suboptimal, and are associated with significant risk of misinterpretation. The aim of this study was to re-assess the existing literature, and to develop a more effective histological method of melanin quantification in human skin. Moreover, we confirm that Warthin-Starry (WS) stain provides a much more sensitive and more specific melanin detection method than the common-place Fontana-Masson (FM) stain. For example, WS staining sensitivity allowed the visualization of melanin even in very pale Caucasian skin that was missed by FM or Von Kossa (VK) stains. From our re-assessment of the histologyrelated literature we conclude that so-called ‘melanin dust’ is most likely an artefact of discoloration due to non-specific silver deposition in the stratum corneum. Unlike FM and VK, WS was not associated with this non-specific stratum corneum darkening, misinterpreted previously as ‘degraded’ or so-called ‘dust’ melanin. Finally, WS melanin particle counts were largely similar to manual counts by transmission electron microscopy, in contrast to both FM and VK. Together these findings allow us to propose a new histology/Image J-informed method for the accurate and precise quantification of epidermal melanin in skin

Tattoo ink nanoparticles in skin tissue and fibroblasts

YesTattooing has long been practised in various societies all around the world and is becoming increasingly common and widespread in the West. Tattoo ink suspensions unquestionably contain pigments composed of nanoparticles, i.e., particles of sub-100 nm dimensions. It is widely acknowledged that nanoparticles have higher levels of chemical activity than their larger particle equivalents. However, assessment of the toxicity of tattoo inks has been the subject of little research and ink manufacturers are not obliged to disclose the exact composition of their products. This study examines tattoo ink particles in two fundamental skin components at the nanometre level. We use atomic force microscopy and light microscopy to examine cryosections of tattooed skin, exploring the collagen fibril networks in the dermis that contain ink nanoparticles. Further, we culture fibroblasts in diluted tattoo ink to explore both the immediate impact of ink pigment on cell viability and also to observe the interaction between particles and the cells

Photobiomodulation of human dermal fibroblasts in vitro: decisive role of cell culture conditions and treatment protocols on experimental outcome

YesPhotobiomodulation-based (LLLT) therapies show tantalizing promise for treatment of skin diseases. Confidence in this approach is blighted however by lamentable inconsistency in published experimental designs, and so complicates interpretation. Here we interrogate the appropriateness of a range of previously-reported treatment parameters, including light wavelength, irradiance and radiant exposure, as well as cell culture conditions (e.g., serum concentration, cell confluency, medium refreshment, direct/indirect treatment, oxygen concentration, etc.), in primary cultures of normal human dermal fibroblasts exposed to visible and near infra-red (NIR) light. Apart from irradiance, all study parameters impacted significantly on fibroblast metabolic activity. Moreover, when cells were grown at atmospheric O2 levels (i.e. 20%) short wavelength light inhibited cell metabolism, while negligible effects were seen with long visible and NIR wavelength. By contrast, NIR stimulated cells when exposed to dermal tissue oxygen levels (approx. 2%). The impact of culture conditions was further seen when inhibitory effects of short wavelength light were reduced with increasing serum concentration and cell confluency. We conclude that a significant source of problematic interpretations in photobiomodulation reports derives from poor optimization of study design. Further development of this field using in vitro/ex vivo models should embrace significant standardization of study design, ideally within a design-of-experiment setting

Autoantibodies to Hair Follicles in C3H/HeJ Mice With Alopecia Areata–Like Hair Loss

We have previously described spontaneous but reversible hair loss that clinically and histologically resembles human alopecia areata in a colony of C3H/HeJ mice. Alopecia areata in humans is associated with antibodies to hair follicles. This study was conducted to determine whether C3H/HeJ mice with hair loss have a similar abnormal antibody response to hair follicles. Eighteen C3H/HeJ mice with alopecia, 12 unaffected littermates, and 15 control mice were examined for circulating antibodies to C3H/HeJ anagen hair follicles by indirect immunofluorescence and against extracts of isolated C3H/HeJ and human anagen hair follicles by immunoblotting. Using both procedures, antibodies to anagen hair follicles were present in all C3H/HeJ mice with alopecia but in none of the control mice. The antibodies were also present in some unaffected C3H/HeJ littermates but were absent in mice of an unrelated strain with inflammatory skin disease and alopecia, indicating that their appearance did not result from the hair loss. These antibodies reacted to hair follicle–specific antigens of 40–60kDa present in murine and human anagen hair follicles. These antigens were also reactive with human alopecia areata antibodies. Some of the antibodies in both C3H/HeJ mice and humans with alopecia areata reacted to antigens of 44 and 46 kDa, which were identified as hair follicle–specific keratins. This study indicates that C3H/HeJ mice with hair loss have circulating antibodies to hair follicles similar to those present in humans with alopecia areata. These findings confirm that these mice are an appropriate model for human alopecia areata and support the hypothesis that alopecia areata results from an abnormal autoimmune response to hair follicles

Hair-Cycle-Associated Remodeling of the Peptidergic Innervation of Murine Skin, and Hair Growth Modulation by Neuropeptides

As the neuropeptide substance P can manipulate murine hair growth in vivo, we here further studied the role of sensory neuropeptides in hair follicle biology by determining the distribution and hair-cycle-dependent remodeling of the sensory innervation in C57BL/6 mouse back skin. Calcitonin-gene-related peptide, substance P, and peptide histidine methionine (employed as vasoactive intestinal peptide marker) were identified by immunohistochemistry. All of these markers immunolocalized to bundles of nerve fibers and to single nerve fibers, with distinct distribution patterns and major hair-cycle-associated changes. In the epidermis and around the distal hair follicle and the arrector pili muscle, only calcitonin-gene-related peptide immunoreactive nerve fibers were visualized, whereas substance P and peptide histidine methionine immunoreactive nerve fibers were largely restricted to the dermis and subcutis. Compared to telogen skin, the number of calcitonin-gene-related peptide, substance P, and peptide histidine methionine immunoreactive single nerve fibers increased significantly (p < 0.01) during anagen, including around the bulge region (the seat of epithelial stem cells). Substance P significantly accelerated anagen progression in murine skin organ culture, whereas calcitonin-gene-related peptide and a substance-P-inhibitory peptide inhibited anagen (p < 0.05). The inhibitory effect of calcitonin-gene-related peptide could be antagonized by coadministrating substance P. In contrast to substance P, calcitonin-gene-related peptide failed to induce anagen when released from subcutaneous implants. This might reflect a differential functional assignment of the neuropeptides calcitonin-gene-related peptide and substance P in hair growth control, and invites the use of neuropeptide receptor agonists and antagonists as novel pharmacologic tools for therapeutic hair growth manipulation