Pharmacologic interventions in aging hair

Abstract: The appearance of hair plays an important role in people's overall physical appearance and self-perception. With today's increasing life-expectations, the desire to look youthful plays a bigger role than ever. The hair care industry has become aware of this and is delivering active products directed towards meeting this consumer demand. The discovery of pharmacological targets and the development of safe and effective drugs also indicate strategies of the drug industry for maintenance of healthy and beautiful hair. Hair aging comprises weathering of the hair shaft, decrease of melanocyte function, and decrease in hair production. The scalp is subject to intrinsic and extrinsic aging. Intrinsic factors are related to individual genetic and epigenetic mechanisms with interindividual variation: prototypes are familial premature graying, and androgenetic alopecia. Currently available pharmacologic treatment modalities with proven efficacy for treatment of androgenetic alopecia are topical minoxidil and oral finasteride. Extrinsic factors include ultraviolet radiation and air pollution. Experimental evidence supports the hypothesis that oxidative stress also plays a role in hair aging. Topical anti-aging compounds include photoprotectors and antioxidants. In the absence of another way to reverse hair graying, hair colorants remain the mainstay of recovering lost hair color. Topical liposome targeting for melanins, genes, and proteins selectively to hair follicles are currently under investigation. Keywords: hair weathering, graying, androgenetic alopecia, senescent alopecia, hair antiaging "Aged? But he does not appear aged, just look, his hair has remained young!" -Marcel Proust, Remembrance of Things Past In today's world, physical appearance and the notion of looking young and energetic play a greater role than ever. Hair length, color, and style are important for people's physical appearance and self-perception. The condition and style of hair determine how we discern the people we encounter, and how we are perceived by those we come upon. Hair is not only intended to invoke male recognition of feminine appeal and desirability, but it has even become a predicate upon which social success and career opportunities are based. Our preoccupation with hair is further heightened as our increasing life-expectancy fuels our desire to preserve youthfulness. The study of hair aging focuses on two main streams of interest: on one hand, the aesthetic problem of aging hair and its management, in other words everything that happens outside the skin; on the other hand, the biological problem of aging hair, in terms of microscopic, biochemical (hormonal, enzymatic), and molecular changes, in other words, the "secret life" of the hair follicle in the depth of the skin. Scientists interested in the biology of hair growth and pigmentation have exposed the hair follicle as a highly accessible and unique model that offers unequaled opportunities to the gerontologist for the study of age-related effects

Reversal of canities

1 +VERITAS, White hair turned black. http://query.nytimes.com/mem/archive-free/pdf?_r=1&res=9506E3DF123FE633A25756C0A96E9C946296D6CFAccessed July 23 20092 +Comaish S White scalp hairs turning black—an unusual reversal of the ageing process. Br J Dermatol 1972;86 (5) 513- 514PubMed Link to Article[[XSLOpenURL/10.1111/bjd.1972.86.issue-5]]3 +Tobin DJCargnello JA Partial reversal of canities in a 22-year-old normal Chinese male. Arch Dermatol 1993;129 (6) 789- 791PubMed Link to Article[[XSLOpenURL/10.1001/archderm.1993.01680270133025]]4 +Pattier P Spontaneous repigmentation of white hair [in French]. Ann Dermatol Venereol 2001;128 (10, pt 1) 1082- 1083PubMed5 +Tobin DJPaus R Graying: gerontobiology of the hair follicle pigmentary unit. Exp Gerontol 2001;36 (1) 29- 54PubMed Link to Article[[XSLOpenURL/10.1016/S0531-5565(00)00210-2]]6 +Navarini AANobbe STrueb RM Marie Antoinette syndrome. Arch Dermatol 2009;145 (6) 656PubMed Link to Article[[XSLOpenURL/10.1001/archdermatol.2009.51]

Molecular mechanisms of androgenetic alopecia

Abstract Androgenetic alopecia (AGA) is hereditary and androgen-dependent, progressive thinning of the scalp hair that follows a defined pattern. While the genetic involvement is pronounced but poorly understood, major advances have been achieved in understanding principal elements of the androgen metabolism involved: androgen-dependent processes are predominantly due to the binding of dihydrotestosterone (DHT) to the androgen receptor (AR). DHT-dependent cell functions depend on the availability of weak androgens, their conversion to more potent androgens via the action of 5alpha-reductase, low enzymatic activity of androgen inactivating enzymes, and functionally active AR present in high numbers. The predisposed scalp exhibits high levels of DHT, and increased expression of the AR. Conversion of testosterone to DHT within the dermal papilla plays a central role, while androgen-regulated factors deriving from dermal papilla cells are believed to influence growth of other components of the hair follicle. Current available treatment modalities with proven efficacy are oral finasteride, a competitive inhibitor of type 2 5a-reductase, and topical minoxidil, an adenosine-triphosphate-sensitive potassium channel opener which has been reported to stimulate the production of vascular endothelial growth factor in cultured dermal papilla cells. Since the clinical success rate of treatment of AGA with modulators of androgen metabolism or hair growth promoters is limited, sustained microscopic follicular inflammation with connective tissue remodeling, eventually resulting in permanent hair loss, is considered a possible cofactor in the complex etiology of AGA.

Molecular mechanisms of androgenetic alopecia

Abstract Androgenetic alopecia (AGA) is hereditary and androgen-dependent, progressive thinning of the scalp hair that follows a defined pattern. While the genetic involvement is pronounced but poorly understood, major advances have been achieved in understanding principal elements of the androgen metabolism involved: androgen-dependent processes are predominantly due to the binding of dihydrotestosterone (DHT) to the androgen receptor (AR). DHT-dependent cell functions depend on the availability of weak androgens, their conversion to more potent androgens via the action of 5alpha-reductase, low enzymatic activity of androgen inactivating enzymes, and functionally active AR present in high numbers. The predisposed scalp exhibits high levels of DHT, and increased expression of the AR. Conversion of testosterone to DHT within the dermal papilla plays a central role, while androgen-regulated factors deriving from dermal papilla cells are believed to influence growth of other components of the hair follicle. Current available treatment modalities with proven efficacy are oral finasteride, a competitive inhibitor of type 2 5a-reductase, and topical minoxidil, an adenosine-triphosphate-sensitive potassium channel opener which has been reported to stimulate the production of vascular endothelial growth factor in cultured dermal papilla cells. Since the clinical success rate of treatment of AGA with modulators of androgen metabolism or hair growth promoters is limited, sustained microscopic follicular inflammation with connective tissue remodeling, eventually resulting in permanent hair loss, is considered a possible cofactor in the complex etiology of AGA.

Oxidative Stress in Ageing of Hair

Experimental evidence supports the hypothesis that oxidative stress plays a major role in the ageing process. Reactive oxygen species are generated by a multitude of endogenous and environmental challenges. Reactive oxygen species or free radicals are highly reactive molecules that can directly damage cellular structural membranes, lipids, proteins, and DNA. The body possesses endogenous defence mechanisms, such as antioxidative enzymes and non-enzymatic antioxidative molecules, protecting it from free radicals by reducing and neutralizing them. With age, the production of free radicals increases, while the endogenous defence mechanisms decrease. This imbalance leads to the progressive damage of cellular structures, presumably resulting in the ageing phenotype. Ageing of hair manifests as decrease of melanocyte function or graying, and decrease in hair production or alopecia. There is circumstantial evidence that oxidative stress may be a pivotal mechanism contributing to hair graying and hair loss. New insights into the role and prevention of oxidative stress could open new strategies for intervention and reversal of the hair graying process and age-dependent alopecia

Why Henry III of Navarre’s Hair Probably did not Turn White Overnight

Although a rare event, sudden whitening of hair (canities subita) has reportedly affected a number of well-known historical figures, usually in relation to dramatic events in their lives. Although early accounts are substantiated by more recent case reports in scientific literature, we suspect that the phenomenon is not only used as a literary means in fiction, with the aim of dramatizing, but probably also in historical accounts. For this purpose, we examine the case history of Henry III of Navarre who allegedly turned white on the evening of the Saint Bartholomew’s day massacre, and challenge this claim, due to inconsistencies in his biography, with the current pathophysiological understanding of canities subita

[Psoriasis]

Die Psoriasis ist eine Hautkrankheit, die sich nach außen hin durch scharf begrenzte, gerötete Plaques infolge entzündlicher Hautinfiltration und einer fest haftenden, silbrig weißen Schuppung infolge epidermaler Hyperproliferation und Parakeratose auszeichnet. Der Name leitet sich von πσόρα, Krätze, ab, und die Erkrankung wurde im Altertum mit Aussatz gleichgesetzt, was die Bedeutung vom Juckreiz bzw. die soziale Stigmatisierung unterstreicht. Heute wird die Psoriasis als primäre, autoimmun und genetisch bedingte, T-Zell-vermittelte Systemkrankheit mit entzündlichen Manifestationen an Haut, Nägeln und Gelenken (Psoriasis Arthritis) sowie einer Reihe von Ko-Morbiditäten aufgefasst. Dementsprechend sind die therapeutischen Ansätze antientzündlich, proliferationshemmend und keratolytisch bzw. richten sich nach dem Schweregrad der Erkrankung, bezogen auf die Flächenausdehnung und Einzeleffloreszenz (PASI), Beeinträchtigung der Lebensqualität (DLQI) und besondere Lokalisationen (Psoriasis inversa, Palmoplantarpsoriasis, Nagelpsoriasis), sowie Patientenalter und Ko-Morbiditäten (Arthritis, metabolisches Syndrom, kardiovaskuläre Erkrankungen, Depression, Suizidalität). In 0 % liegt eine leichte Psoriasis vor, die mittels äußerlicher (Kortikosteroide, Vit. D-Analoga) und Phototherapie (PUVA, nbUVB) hinreichend behandelt werden kann, 20 % benötigen aufgrund der Ausdehnung bzw. Schwere der Erkrankung eine systemische Therapie (Acitretin, Methotrexat, Ciclosporin) oder Therapie mittels der neuen Substanzklasse der Biologics. Vor allem bei den schweren Formen der Psoriasis sind der psychischer Leidensdruck, die Ko-Morbiditäten und medizinökonomische Überlegungen im individuellen Behandlungsplan mit zu berücksichtigen. [English abstract]Psoriasis is a skin disease typically presenting with sharply demarcated, inflammatory, erythematous plaques with characteristic silver-white scaling due to epidermal hyperproliferation and parakeratosis secondary to the inflammation. The name derives from pisigmaomicronrhoalpha (mange or scabies), and in ancient times the disease was confused with leprosy resulting in expulsion from society. Hence, both itching and social stigmatization are major problems affecting patients with psoriasis. Today, psoriasis is recognized as a genetically determined, autoimmune, T cell mediated systemic disease manifesting on the skin, nails and joints and associated with a number of co-morbidities. Accordingly, therapeutic strategies are antiinflammatory, antiproliferative and keratolytic. The extent and severity of disease (PASI), impairment of life quality (DLQI), and affected anatomic regions (inverse, palmoplantar, nails) as well as co-morbidities (arthritis, metabolic syndrome, cardiovascular disease, depression) determine the therapy. In 80 % of cases psoriasis is mild or moderate and sufficiently treated with topical corticosteroids, vitamin D-analogues, and phototherapy. 20 % of patients suffer from severe psoriasis, necessitating systemic drugs such as acitretin, methotrexate, ciclosporin A or the newer biologic agents. Especially in severe psoriasis, psychological strain, co-morbidities, and medico-economic aspects must be taken into account