Aging in hair follicle stem cells and niche microenvironment

Hair graying and hair loss are prominent and common characteristics of the elderly population. In some individuals these processes can significantly impact their quality of life, leading to depression, anxiety and other serious mental health problems. Accordingly, there has been much interest in understanding the complex physiological changes within the hair follicle in the aging individual. It is now known that hair follicles represent a prototypical stem cell niche, where both micro‐ and macroenvironmental influences are integrated alongside stem cell–stem cell and stem cell–stem niche interactions to determine hair growth or hair follicle senescence. Recent studies have identified imbalanced stem cell differentiation and altered stem cell activity as important factors during hair loss, indicating new avenues for the development of therapeutic agents to stimulate hair growth. Here, we pull together the latest findings on the hair follicle stem cell niche and the multifactorial interactions underlying the various forms of hair loss.     

Healthy Hair: What Is it?

Shiny hair with a smooth texture and clean-cut ends or tapered tips is generally perceived to be healthy. Hair texture and shine relate to hair surface properties, whereas the integrity of hair ends relates to the hair cortex. Hair can be straight, wavy or curly, blonde, black, brown, red, gray white, and its natural variations are important to our identity. Manipulation of the normal structure of the hair shaft is epidemic and dictated by culture, fashion, and above all, celebrity. Although cosmetic procedures are intrinsically safe, there is potential for damage to the hair. Loss of lustre, frizz, split ends, and other hair problems are particularly prevalent among people who repeatedly alter the natural style of their hair or among people with hair that is intrinsically weak. This may be due to individual or racial variation or less commonly an inherited structural abnormality in hair fiber formation. Hair health is also affected by common afflictions of the scalp as well as age-related phenomena such as graying and androgenetic alopecia. Hair products that improve the structural integrity of hair fibers and increase tensile strength are available, as are products that increase hair volume, reduce frizz, improve hair manageability, and stimulate new hair growth.     

A bald statement — Current approaches to manipulate miniaturisation focus only on promoting hair growth

Hair plays a large part in communication and society with its role changing through time and across cultures. Most people do not leave the house before combing their hair or shaving their beard and for many hair loss or irregular hair growth can have a significant impact on their psychological health. Somewhat unsurprisingly, according to GMR Data, today’s global hair care industry is worth an estimated $87 Billion, with hair loss estimated at $2.8 Billion. Considering that no current hair loss‐related products can completely reverse hair loss, it is reasonable to believe this market could expand significantly with the discovery of a comprehensive therapy. As such, a great deal of research focuses on overcoming hair loss, and in particular, a common form of hair loss known as androgenetic alopecia (AGA) or male pattern baldness. In AGA, hair follicles miniaturise in a large step change from a terminal to a vellus state. Within this viewpoint article, we discuss how influx and efflux of cells into and out from the dermal papilla (DP) can modulate DP size during the hair cycle. As DP size is positively correlated with the size of the hair fibre produced by a follicle, we argue here that therapies for treating AGA should be developed which can alter DP size, rather than just promote hair growth. We also discuss current therapeutics for AGA and emphasise the importance of using the right model systems to analyse miniaturisation.     

Basic hair transplantation: 2007

ABSTRACT:  The most common form of hair loss is androgenic alopecia that affects at least half of the male population by age 50 is speculated to be caused by a change in the balance of androgen hormones. Male hair loss occurs in a characteristic pattern of decreased hair growth where hair becomes progressively finer, less pigmented, ceasing growth completely, and then becoming dislodged from the scalp. Hair loss to some patients is a serious issue that can impart a social and psychologic impact on their life. Hair restoration and transplantation have the potential to provide a solution for this problem; however, it is not effective for every patient. This review article looks at past hair transplantation techniques and studies that have provided the basis for current procedures and new research at how to target successful results.     

The role of telomerase in hair growth and relevant disorders: A review

Background

Hair diseases may present with hair loss, hirsutism, hair melanin abnormalities and other manifestations. Hair follicles are known as mini-organs that undergo periodic remodeling, and their constant regeneration in vivo reflects interesting anti-aging functions. Telomerase prevents cellular senescence by maintaining telomere length, but its excessive proliferation in cancer cells may also induce cancer. However, the effects of telomerase in hair growth have rarely been reported.

Methods

In this study, we reviewed the role of telomerase in hair growth and the effects of hair disorders through literature search and analysis.

Results

There is growing evidence that telomerase plays an important role in maintaining hair follicle function and proliferation. Changes in telomerase levels in hair follicles have also been found in a variety of hair disorders.

Conclusion

Telomerase plays a positive role in hair growth and is expected to become a new target for the treatment of alopecia or other hair diseases in the future.     

毛囊间充质干细胞的研究进展

 毛囊间充质干细胞（HFMSCs）是一类具有自我再生能力、高度增殖潜能、可多向分化且来源丰富的慢周期标记滞留细胞,可促进表皮、毛囊和皮脂腺再生。得益于其来源丰富、易获得、可于体外扩增、无需基因操作、不会形成肿瘤和无伦理限制等特点,毛囊间充质干细胞在再生医学中具有重要优势。Wnt、Shh、Notch和BMP等信号通路之间的协同和拮抗作用在干细胞稳态调节、表皮发育和毛囊再生过程中发挥至关重要的作用,这些途径的失调可能导致毛发脱落或者肿瘤的发生。本文综述毛囊间充质干细胞的分类及其特异性生物标记物、毛囊间充质干细胞的活化以及影响毛发再生的生物分子途径,为毛发疾病的治疗提供新的线索和靶点。     

Histopathology of aging of the hair follicle

Hair follicles experience several changes with aging, the most noticeable of which is graying of the hair shaft due to loss of melanin. Additional changes in the diameter and length of the hair have contributed to the concept of senescent alopecia, which is different from androgenetic alopecia according to most. Graying happens in most individuals, although in different grades and starting at different ages. It is related to a decrease in the number and activity of the melanocytes of the hair bulb, which eventually completely disappear from the bulb of the white hair. Residual non‐active melanocytes remain in the outer root sheath and in the bulge, which allows for repigmentation of the hair under certain stimuli or conditions.     

Differential diagnosis of hair loss in children

Hair loss in childhood covers a broad differential diagnosis and often presents the involved dermatologist and pediatrician with a diagnostic and therapeutic challenge. Correct classification of the hair disease, especially in the case of underlying genetic syndromes, metabolic defects or endocrine disorders, is often an important prerequisite for continued normal physical and mental development of the young patients. Dealing with hair loss in childhood, one should differentiate between congenital and acquired diseases. The clinical manifestation profile, the age of the patient when the initial manifestation occurred, and the presence of associated symptoms are important for the classification of the hair disease. In the present paper, a classification of hair loss in childhood based on clinical appearance, age of onset and associated symptoms is proposed as a guide for the evaluation of hair loss and alopecia in childhood.     

Clinical study on the efficacy and tolerability of a topical regenerative treatment in patients with telogen effluvium and mild androgenetic alopecia

Hair loss may change the quality of life since modern society considers hair an essential element in beauty definition. The most common causes of hair loss are androgenetic alopecia (AGA) and telogen effluvium (TE). AGA requires a lifetime use of minoxidil or finasteride (and sometimes they lose efficacy over the years), whereas TE has no standardized therapy available. Our study focuses on a novel topical regenerative preparation that, by mimicking autologous PRP, can safely and efficiently improve hair loss in patients affected by TE and AGA.     

Application of internal wool lipids to hair

Purpose: Hair lipids can contribute to physicochemical phenomena such as diffusion, cell cohesion and mechanical strength, although lipids occur at much lower levels (1–6% dry weight) than proteins (>90%).Hair lipids can be diminished by hair washing and submission to chemical treatments. Studies have shown that internal wool lipids (IWL) resemble those membranes of other keratinic tissues such as human hair or stratum corneum. Results: In this work, the IWL, in the form of liposomes or from an emulsion system, were applied to untreated hair fibres and also treated hair fibres. The results showed that application of IWL to pretreated hair samples lead to an improvement in mechanical strength properties of the fibres when the IWL were applied structured as liposomes. Differential scanning calorimetry studies demonstrated that the application of IWL to pretreated hair sample led to a slight increase in the crystalline material of the fibres. Moreover, scanning electron microscopy studies showed that application of IWL liposomes to damaged hair fibres lead to an improvement of the cuticle scale, demonstrating the importance of the use of a delivery vehicle with a bilayer structure similar to the one present in the hair fibre to restore the natural properties of the fibre.     

Interrogating the integument: the role of the epidermis in hair induction

Hair follicle development is driven by interactions between the epithelium and underlying mesenchyme. These reciprocal interactions are essential for development, as a lack of response from either the mesenchyme or epithelium results in arrested growth. A large body of research has focused on the role of mesenchymal cells during hair follicle development and their inductive properties for hair neogenesis. In this commentary, the role of the epidermis during hair follicle induction will be discussed.     

Hair density, hair diameter and the prevalence of female pattern hair loss

BACKGROUND: Female pattern hair loss is common but estimates of its prevalence have varied widely. The relationships between the clinical diagnosis of female pattern hair loss and objective measurements of hair density and hair diameter have not previously been evaluated. OBJECTIVES: To determine the prevalence of female pattern hair loss and to relate the clinical findings to hair density and hair diameter. METHODS: We examined 377 women, aged 18--99 years, who presented to a general dermatology clinic with complaints unrelated to hair growth (the unselected sample). A second group of 47 women referred with typical female pattern hair loss was included in analyses of the relationships between hair density, hair diameter and the clinical diagnosis. Hair density was measured using a photographic method. In each subject the major and minor axis diameters were measured in a random sample of 50 hairs. RESULTS: Six per cent of women aged under 50 years were diagnosed as having female pattern hair loss, increasing to 38% in subjects aged 70 years and over. The mean +/- SEM hair density was 293 +/- 61.3 hairs cm(-2) at age 35 years, falling to 211 +/- 55.1 hairs cm(-2) at age 70 years. Hair density showed a normal distribution in the unselected sample. Most women classified as having female pattern hair loss had hair densities within the lower half of the normal distribution. The perception of hair loss was determined mainly by low hair density (ANOVA P < 0.001), but there was overlap in hair density between women classified as having Ludwig I hair loss and the no hair loss group, which was partly accounted for by differences in mean hair diameter (ANOVA P < 0.001). Low hair density was associated with fewer hairs of all diameters. CONCLUSIONS: Hair density in women is distributed as a normal variable, indicating that it is determined as a multifactorial trait. Women with female pattern hair loss have a hair density which falls below the mean but lies within the spectrum of the normal distribution, although other factors, including hair diameter, may affect the subjective impression of hair loss. The hair diameter data suggest that low hair density is not due to progressive diminution in hair follicle size and that follicular miniaturization may occur within the space of a single hair cycle.     

African hair growth parameters

BACKGROUND: Hair growth parameters have been studied mostly in caucasian hair, whereas few data on African hair have been reported in the literature. OBJECTIVES: To evaluate hair growth characteristics of African volunteers born in Africa. METHODS: Thirty-eight young adults (19 women, 19 men, mean +/- SD age 27 +/- 10 years), native of central and western Africa, took part in the study. Phototrichograms were performed in order to record three parameters of hair growth: hair density, telogen percentage and rate of growth. For each volunteer, three regions of the scalp, namely vertex, temporal and occipital areas, were assessed. RESULTS: Hair density varied from 90 to 290 hairs cm(-2), with higher counts on the vertex. No significant difference between men and women was recorded. Telogen percentage showed wide variations, from 2 to 46%, with higher levels on the temporal area and in men. The rate of growth fluctuated from 150 to 363 microm day(-1) with no difference related either to gender or to scalp region. These data were compared with those previously obtained in caucasian volunteers of comparable age, and showed significant differences between the two ethnic groups in all three parameters studied. Hair density in African volunteers was lower than that in caucasians (mean +/- SD 190 +/- 40 and 227 +/- 55 hairs cm(-2), respectively). African hair grew at a much slower rate than caucasian hair (mean +/- SD 256 +/- 44 vs. 396 +/- 55 microm day(-1)), and telogen counts were frequently higher in African hair (mean +/- SD 18 +/- 9% vs. 14 +/- 11%). CONCLUSIONS: This study demonstrated significant differences between African and caucasian hair growth parameters, which might suggest a trend towards increased hair loss in Africans, even though it contrasts with a lower and slower incidence of the development of alopecia in Africans.     

High-dose proinflammatory cytokines induce apoptosis of hair bulb keratinocytes in vivo

BACKGROUND: Hair loss following skin inflammation may in part be mediated by keratinocyte (KC) apoptosis. While the effects of different cytokines or other apoptosis stimulating agents such as interferon (IFN)-gamma or tumour necrosis factor (TNF)-alpha on KC apoptosis in vitro have been addressed in several studies, little is known about the effects of proinflammatory cytokines on KC apoptosis in vivo. OBJECTIVES: To study the effects of intradermally injected TNF-alpha, interleukin (IL)-1beta and IFN-gamma on KC apoptosis in the back skin of C57BL/6 mice. METHODS: Apoptosis in epidermal and hair bulb KCs was analysed by immunohistology using TUNEL staining. RESULTS: Injection of TNF-alpha induced a significantly higher number of apoptotic cells within the epidermis than vehicle; all three proinflammatory cytokines together further increased their number. Intrafollicular hair bulb KCs were much more susceptible to apoptosis induction by TNF-alpha or IL-1beta; their injection significantly upregulated apoptosis after 6 h, which was further increased after 24 h. The combination of all cytokines together accelerated intrafollicular apoptosis after 6 h by doubling the number of apoptotic cells per hair bulb, compared with the effects of TNF-alpha or IL-1beta alone. CONCLUSIONS: These data suggest that programmed cell death of proliferating KCs in vivo can be induced by proinflammatory cytokines.     

Current standards in the diagnostics and therapy of hair diseases – hair consultation

Hair and scalp diseases present an extensive diagnostic and therapeutic task. Treating them is often a challenge for the physician in daily practice. Unclear diagnoses, chronic conditions with long‐lasting therapies and the uncertainty of the patient may often lead to unsatisfying situations for both the patient as well as the doctor. The complaints can be divided into (1) hair loss, (2) increased hair growth and (3) abnormal hair quality. A structured history and the objectification of the clinical findings with the help of standardized diagnostic methods and score systems or classifications enable a diagnosis in most patients already at the first visit. Moreover, such structured processes strengthen the treatment satisfaction and compliance of both the patient and the therapist. In the meantime, diagnostic measures and clinical practice guidelines are available for the most common hair disorders. Expertise in basic psychosomatic care and an empathetic approach to the fears and concerns as well as practical advice for the daily contact with hair disorders should be integrated as separate elements in the management of hair diseases; in most cases they are gratefully welcomed by the patients. The aim of this article is to provide the physician with a guideline for the structured management of a hair patient. An overview of recent new developments and the currently available clinical practice guidelines for diagnosis and therapy of hair disorders is presented.     

Automated body hair counting and length measurement

Background/purpose: Hair loss or hair excess is a common condition. There is a growing need to quantitatively assess the success of interventions aimed at replenishing areas that lack hair or at removing hair from areas such as the back, the legs, or the arms. Non‐invasive methods that do not require staining are highly desirable because the staining process itself may affect the efficacy of the treatment. Methods: We introduce a system based on a flatbed scanner and on novel and sensitive image analysis algorithms to count the number of hairs and their individual length. Additionally, a measure of hair visibility is introduced, which allows assessing objectively the severity of the condition. Results: Our system is able to detect even hairs that are difficult to see to a human observer. It is robust to skin impurities or variations in the skin texture and colour. Scanner imaging ensures a sharp image over the whole field. The system analyses on the order of two images per minute, making it suitable for large clinical studies. Counts delivered by a human counter vs. the software were within 10% of each other (N=12). Conclusion: Based on our results, we expect that the software will be useful to a number of researchers investigating medical and cosmetic issues involving objective assessment of pilosity. The algorithm itself may be of use for other applications.     

Wigs and hairpieces: Evaluating dermatologic issues

Hair is an important feature of self-image, and hair loss can have a devastating impact on a person's pychological well-being. In recent years, there has been an explosion of research in the understanding of various hair disorders, but unfortunately there has not been a major breakthrough and not much has changed in terms of therapeutic options available to patients with extensive hair loss. As professionals, we need to understand the social significance of hair in relation to a person's outward presentation and social interactions. We must minimize the distress alopecia can cause by providing up-to-date information to enable them to prepare for and minimize the psychological consequences of hair loss.     

Wanted,dead and alive: Why a multidisciplinary approach is needed to unlock hair treatment potential

Human recorded history is littered with attempts to improve the perceived appearance of scalp hair. Throughout history, treatments have included both biological and chemical interventions. Hair “quality” or “perceived appearance” is regulated by multiple biological intervention opportunities: adding more hairs by flipping follicles from telogen to anagen, or delaying anagen follicles transiting into catagen; altering hair “apparent amount” by modulating shaft diameter or shape; or, in principle, altering shaft physical properties changing its synthesis. By far the most common biological intervention strategy today is to increase the number of hairs, but to date this has proven difficult and has yielded minimal benefits. Chemical intervention primarily consists of active material surface deposition to improve shaft shine, fibre‐fibre interactions and strength. Real, perceptible benefits will best be achieved by combining opportunity areas across the three primary sciences: biology, chemistry and physics. Shaft biogenesis begins with biology: proliferation in the germinative matrix, then crossing “Auber's Critical Line” and ceasing proliferation to synthesize shaft components. Biogenesis then shifts to oxidative chemistry, where previously synthesized components are organized and cross‐linked into a shaft. We herein term the crossing point from biology to chemistry as “The Orwin Threshold.” Historically, hair biology and chemistry have been conducted in different fields, with biological manipulation residing in biomedical communities and hair shaft chemistry and physics within the consumer care industry, with minimal cross‐fertilization. Detailed understanding of hair shaft biogenesis should enable identification of factors necessary for optimum hair shaft production and new intervention opportunities.     

Usefulness of TrichoScan professional in the evaluation of hair loss in females. Report of 180 cases

Background TrichoScan Professional is a computerized program used for digital measurement of hair growth and hair loss. The aim of our study was to undertake an evaluation with TrichoScan Professional of female patients consulting at our hospitals for hair loss. The purpose of our study was to determine whether TrichoScan was able to identify differences in hair parameters that would correlate with the pattern of alopecia or according to the age of the patients evaluated. Material and methods One hundred‐eighty women that consulted consecutively for loss of hair were included. Patients were aged between 8 and 85 years (mean age 36 years). Data including age, the number of hairs, hair density per square centimetre, anagen and telogen percentage and percentage of terminal and miniaturized hair were analysed. Results Results observed with TrichoScan were as below: number of hairs (mean 154.9; range 34–316). Hair density per square centimetre (mean 239; range 52–486). Hair in anagen phase (mean 62.4%; range 9–93%). Hair in telogen phase (mean 37.4%; range 7–91%). Terminal hair (mean 95.2%; range 82–100%). Vellus hair (mean 4.7%; range 0–17%). Pearson′s correlation test was used to measure the strength of the association of age with the rest of parameters. The statistical analysis showed a significant correlation between age and both the number of hairs and the hair density per square centimetre. However, no significant correlation between age and rest of the parameters was observed. Conclusions TrichoScan Professional may help to quantify hair density and in our sample, this was the only parameter showing a significant decrease according to age in various types of alopecia affecting the females.     

Getting under the skin of hair aging: the impact of the hair follicle environment

Like the skin, our hair shows striking changes with age, producing hairs with altered diameter, lustre and texture. The biology of hair aging has focused predominately on various aspects of the hair cycle, follicle size and the fibre produced, but surprisingly the impact of the aging scalp dermal environment on the hair follicle and fibre has been generally overlooked. Hair loss affects both sexes with incidence increasing with age. In men, male pattern-balding (androgenetic alopecia) is driven by androgens and follows a specific pattern of frontotemporal and vertex regression. Women also experience female pattern hair loss (FPHL), presenting as more general, diffuse hair thinning. Hair thinning in women is commonly associated with the menopause, corresponding with other age-related changes in skin. The rapidly growing hair follicle undergoes continued renewal throughout the life span of an individual, where it is exposed to a substantial number of extrinsic and intrinsic stressors. As the hair follicle sits deep within the dermis with its bulb residing in the hypodermis, detrimental age-related changes in the surrounding scalp skin may likely disrupt the hair follicle machinery. The impacts of these changes are unknown, but evidence suggests that scalp skin aging and hair follicle aging go hand-in-hand. Herein, we summarize the evidence that the age-related changes observed in sun-exposed human skin also occur in scalp skin and that these changes are likely to play a contributing role in the aging hair phenotype.