Editor’s note: Cosmetics & Toiletries is pleased to welcome Robert J. Dorin, DO, to its lineup of contributors. His articles will provide insights on hair biology in relation to cosmetics and personal care product development.
Hair is a biological fiber composed primarily of dead keratinocytes that fulfill a variety of important roles for mammals—including, but not limited to, insulation, tactile and sensory functions. Of particular interest to humans are the profound effects it has on the perception and portrayal of a persona. Hair, to a large extent, is an extension of identity. It provides vitality and confidence to portray one’s “style” to others. With such far-reaching dynamic psychosocial implications, it is no wonder why such importance is placed on understanding and promoting intrinsic and extrinsic factors that support the health of hair, as well as preventing harm to this coveted biological fiber.
Research traditionally has focused on the inanimate portion of hair, i.e., beyond the follicle, in order to elucidate the physical and chemical properties and characteristics of hair fibers—all with the intent to produce effective shampoos, conditioners, dyes, bleaching agents, perming agents and the like to help enhance hair’s appearance and combat the perception of aging hair. While decades of this research have proven invaluable to the scientific community, and will continue to do so, a paradigm shift has occurred toward understanding the living component within the hair follicle. A molecular biology revolution has emerged, and promises new strategies in understanding and potentially combating the aging process of hair cells.
This article will consider effects and possible mechanisms of aging in the hair follicle as they relate to the senescence of hair characteristics, hair stem cells and canities. It also will look at a recent study elucidating the effects of bleaching, specifically on inanimate black human hair fibers. Finally, it will cover anti-aging and the concept of antioxidants in human hair.
Growth Characteristics of the Aging Follicle
Hair graying, referred to as canities, and hair loss are usually the first outward visible signs of aging. Hair senescence can cause a general decrease in hair counts and follicle density1, 2 and slow hair growth rates. 3 Also with aging comes an increase in the number of telogen stage or “resting” hairs on the scalp, a decrease in the diameter of hair shafts,1, 2 and a decrease in the anagen or growth phase of hair in men.4 However, one study has demonstrated, both in vivo and in vitro, that gray hair grows faster than hair with pigment.5
Additionally, in elderly subjects, it was found that vellus hairs located on the eyebrow, ear, nasal vestibule, chin and upper lip areas paradoxically were able to convert to terminal hairs.6 This may give hope to individuals afflicted by androgenic alopecia (AGA), as it suggests it may be possible to revert the miniaturized vellus hairs via this unknown pathway into healthy terminal hairs once again.
Senescence of Follicular Stem Cells
It is important for stem cells to be capable of changing their properties in order to meet the regeneration requirements that tissue demands throughout life. This allows for the replacement of cells lost due to injury or disease, or simple homeostatic maintenance. Such function particularly applies to the hair follicle, as it is the only organ in humans known to regenerate cyclically. With aging, the quantity of follicular epithelial stem cells found in the bulge region remains unchanged, while the number of interfollicular stem cells located at the basal layer of the dermis has been found to decline.7, 8 However, it seems the distribution and expression of follicular stem cell markers are unaffected by age.9
In relation, the main function of telomeres is to cap chromosomal ends, protecting them from degradation, fusion and instability. The enzyme telomerase helps to protect against telomere loss, but when telomerase is absent, telomeres shorten with each cell division cycle. Eventually the telomeres reach a critical length that can no longer protect the chromosomal ends. This activates a permanent cell cycle arrest referred to as replicative senescence.
In vitro it has been shown that during the aging process, telomere shortening occurs in follicular stem cells, which leads to impaired clonogenic potential.10 It appears that, as with androgenetic alopecia, the number of stem cells remains constant with age but these cells lose their functional capabilities—and this is what contributes to the miniaturization of hair in AGA. Further investigations have suggested the importance of the extrinsic environment of stem cells and their functional impairment;11 for example, preadipocytes and adipocytes surrounding the follicle appear to exert a regulatory role in the propagation of the hair growth cycle.12, 13
The onset of graying is primarily hereditary. Normally, gray hairs start to appear in one’s mid to late 40s in varying degrees, irrespective of race and gender. A healthy hair follicle without canities exhibits the tight coupling of hair follicle melanocyte proliferation with the early anagen growth phase, followed by maturation of the melanocyte in the middle and late anagen phase, and melanocyte apoptosis during the catagen phase via an unknown mechanism.
Each hair cycle can reconstruct an intact, pigmented terminal hair because the follicle is able to replace these melanocytes from a reserve found in the bulge region of the outer root sheath.14 Although not completely understood, graying is now considered to be caused by the follicle’s inability to maintain amelanotic melanocyte stem cells.14 Hence, canities may result from a genetically controlled mechanism that exhausts the reserves of the melanocyte population, and/or alters the signaling of their migration from the bulge region to the matrix of the bulb. Microphthalmia associated transcription factor (MITF), a key regulator in melanocyte development, and the BCL2 gene, the Wnt signaling pathway and Pax3 protein play roles in melanocyte stem cell maintenance and differentiation.14-17
Despite the biology, observations have rendered anecdotal evidence that hairs known to be gray undergo repigmentation after inflammatory occurrences of the scalp and radiation therapy.18 Other reports indicate partial spontaneous repigmentation in early graying within the same hair growth cycle.19 These occurrences suggest it may be possible to stimulate the melanocytes in the outer root sheath to migrate and differentiate, in turn biologically re-pigmenting graying follicles. Until this effect is produced, however, semi-permanent and permanent hair dyes developed with improved application processes, minimized allergic reactions and reduced incidences of dermatitis, caused by commonly used chemicals such as p-phenylenediamine, would serve the industry well.
Bleaches permanently and irreversibly oxidize the melanin pigment deposited in the cortex of the hair fiber, rendering it colorless. Alkaline solutions soften the hair shaft and cause the cuticles to lift and swell, which allows access to the underlying cortex where the phagocytized melanin resides. The deleterious effects of bleach on the hair shaft can be quite severe, causing hair to become porous, upsetting the moisture content and weakening the cuticle layer so that it can be easily stripped from the cortex. Initial bleaching makes further bleaching more difficult and leaves hair without luster or shine.
In a recent study by Kusuhara,20 numerous deleterious effects to the cuticle and cortex were observed by Raman spectroscopy of the internal structure of virgin black human hair fibers having undergone bleaching treatments. For example, the gauche-gauche-gauche (G-G-G) content of the disulfide bonds of the cuticle and cortex were dramatically decreased. Further, both the β-sheet and/or random coiled content and the α-helix content in the cortex was decreased. Additionally, transmission electron microscopy showed that the proteins in the cell membrane complex, cuticle and cortex were eluted. The author concluded that the disulfide bonds, which had the G-G-G configuration, were broken down and converted to cysteic acid, and the α-helix structure of some of the proteins was altered to the random coil structure and/or removed from the cortex, resulting in a decreased protein density after “excessive” bleaching.
Bleaching of the hair appears to be a double-edged sword; while it provides individuals with the power to change their appearance as desired, it clearly can harm the protein structure and integrity of the hair fiber, ultimately altering the moisture content of the cortex. It strips the fiber of its protective oils and disrupts the protective lipid coatings found in the cuticle cell membrane complex, leading to high porosity and extreme wear on the cuticle, and imparting physical characteristics considered counter-productive to healthy looking and feeling hair.
Since it is apparent that consumers will continue to demand and employ damaging processes such as chemical dyes, bleaches and permanent wave treatments, it raises the need for cosmetic products that will provide desired effects, i.e., colored and curled hair, as well as repair and restore mechanical, morphological, adhesive and frictional properties to overcome the unwanted detrimental side effects of such processes.
Anti-aging in Hair
Oxidation and chronic inflammation are major targets for anti-aging mediation in general, as they are the most caustic factors involved in aging processes. Both the over-reaction and under-reaction of the immune system can result in autoimmune diseases or opportunistic infections, and a chronic inflammatory response to such infections can also speed up the aging process and promote the development of pathological diseases such as cancer. This inflammatory response involves a symphony of cell types, including cytokines, adhesive molecules and chemokines. However, the use of non-steroidal anti-inflammatory medication in addition to natural agents such as phytochemicals have been shown to prevent cancer. 21, 22 In relation, as the personal care industry has witnessed, various anti-inflammatory raw materials have been launched as an approach to anti-aging.
In hair follicles, oxidative cellular metabolism by-products and external stressors, i.e., sunlight, infective pathogens and smoking, ravage the normal homeostasis but antioxidants can combat these assaults on the hair follicle by various mechanisms; e.g., inhibiting oxidative enzymatic reactions, halting reactive oxidation species, or up-regulating antioxidant enzymatic activities. Plant-derived phenolic antioxidants like flavonoids and catechins; epigallocatechin-3-gallate from green tea; and ellagic acid, resveratrol and quercetin from fruits and vegetables all carry antimicrobial and anti-inflammatory abilities, as well as stabilize oxidative free radicals.
While it is known that combinations of antioxidants have beneficial and synergistic effects to counteract inflammation, the preferred route of delivery for these antioxidant cocktails to hair follicles, unfortunately, remains yet to be determined. Topical application via shampoos is unlikely due to the short exposure time with the scalp and dilution by water.23 Improving the efficacy of the systemic delivery of antioxidants to hair follicles is presently being investigated.24
The significant increase and continued use of hair treatments such as bleaching and dyeing to combat the onset of canities creates a greater demand for cosmetic hair products that deliver the desired effect as well as facilitate repair and minimize the adverse effects relating to the mechanical, morphological, frictional and tribological properties of hair. Such effects on the structure and integrity of the hair fiber necessitates further traditional research on the inanimate portion of the hair in order to elucidate how to overcome or circumvent the shortcomings of dyeing and bleaching.
The molecular biology revolution has ensued and promises new strategies in combating the aging process of hair cells, with the paradigm shift toward understanding the living component of the hair follicle. There is growing evidence that persistent inflammation plays a critical role in the aging of hair and its related diseases. With further research, the “inflamm’aging” mostly caused by an imbalance of oxidation versus anti-oxidation response could hopefully be targeted as an anti-aging intervention. Research with nutraceuticals (i.e., vitamins, C, D and E; polyphenols; etc.) have already been shown to provide some anti-aging effects in skin, but further research and development is needed in order to include related nutraceuticals in the prevention and treatment of aging in hair, and to elucidate their efficacy and discover practical delivery systems that work. Maybe one day, canities will be preventable or reversible through the use of anti-inflammatory and anti-aging interventions rather than relying on dyeing alone.
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- P Mirmirani et al, Hair growth parameters in pre- and postmenopausal women, in: RM Trueb and DJ Tobin, eds, Aging Hair, New York, Springer (2010)
- D Van Neste, Thickness, medullation and growth rate of female scalp hair are subject to significant variation according to pigmentation and scalp location during aging, Eur J Dermatol 14 28–32 (2004)
- M Courtois, G Loussouarn, C Hourseau and JF Grollier, Aging and hair cycles, Br J Dermatol 132 86–93 (1995)
- D Van Neste and DJ Tobin, Hair cycle and hair pigmentation: Dynamic interactions and changes associated with aging, Micron 35 193–200 (2004)
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- M Dunnwald, S Chinnathambi, D Alexandrunas and JR Bickenbach, Mouse epidermal stem cells proceed through the cell cycle, J Cell Physiol 195 194-201 (2003)
- SW Youn et al, Cellular senescence induced loss of stem cell proportion in the skin in vitro, J Dermatol Sci 35 113–23 (2004)
- L Rittie, SW Stoll, S Kang, JJ Voorhees and GJ Fisher, Hedgehog signaling maintains hair follicle stem cell phenotype in young and aged human skin, Aging Cell 8 738–51 (2009)
- I Flores, A Canela, E Vera, A Tejera, G Cotsarelis and MA Blasco, The longest telomeres: A general signature of adult stem cell compartments, Genes Dev 22 654–67 (2008)
- CC Chen and CM Chuong, Multi-layered environmental regulation on the homeostasis of stem cells: The saga of hair growth and alopecia, J Dermatol Sci 66 33–11 (2012)
- E Festa et al, Adipocyte lineage cells contribute to the skin stem cell niche to drive hair cycling, Cell 146 761–71 (2011)
- MV Plikus et al, Cyclic dermal BMP signaling regulates stem cell activation during hair regeneration, Nature 451 340–4 (2008)
- EK Nishimura, SR Granter and DE Fisher, Mechanisms of hair graying: Incomplete melanocyte stem cell maintenance in the niche, Science 307 720–4 (2005)
- SS Mak, M Moriyama, E Nishioka, M Osawa and S Nishikawa, Indispensable role of Bcl2 in the development of the melanocyte stem cell, Dey Biol 291 144–53 (2006)
- D Lang et al, Pax3 functions at a nodal point in melanocyte stem cell differentiation, Nature 433 884–7 (2005)
- JD Kubic, KP Young, RS Plummer, AE Ludvik and D Lang, Pigmentation PAX-ways: The role of Pax3 in melanogenesis, melanocyte stem cell maintenance, and disease, Pigment Cell Melanoma Res 21 627–45 (2008)
- M Shetty, Radiation therapy activates melanocytes in hair, Br Med J 311 1582 (1995)
- DJ Tobin and JA Cargnello, Partial reversal of canities in a twenty-two year old Chinese male, Arch Dermatol 129 789–791 (1992)
- A Kuzuhara, Analysis of internal structure changes in black human hair keratin fibers resulting from bleaching treatments using Raman spectroscopy, J Molec Structure 1047 186–193 (2013)
- SA Johannesdottir, ET Chang, F Mehnert, M Schmidt, AB Olesen and HT Sorensen, Nonsteroidal anti-inflammatory drugs and the risk of skin cancer: A population-based case-control study, Cancer 18(19) 4768–7 (2012)
- FR Saunders and HM Wallace, On the natural chemoprevention of cancer, Plant Physiol Biochem 48 621–6 (2010)
- RM True, Pharmacologic interventions in aging hair, Clin Interv Aging 1 121–9 (2006)
- AK Greul et al, Photoprotection of UV-irradiated human skin: An antioxidative combination of vitamins E and C, carotenoids, selenium and proacnthocyanidins, Skin Pharmacol Appl Skin Physiol 15 307–15 (2002)