Towards a “free radical theory of graying”: melanocyte apoptosis in the aging human hair follicle is an indicator of oxidative stress induced tissue damage

Abstract

Oxidative stress is generated by a multitude of environmental and endogenous challenges such as radiation, inflammation, or psychoemotional stress. It also speeds the aging process. Graying is a prominent but little understood feature of aging. Intriguingly, the continuous melanin synthesis in the growing (anagen) hair follicle generates high oxidative stress. We therefore hypothesize that hair bulb melanocytes are especially susceptible to free radical-induced aging. To test this hypothesis, we subjected human scalp skin anagen hair follicles from graying individuals to macroscopic and immunohistomorphometric analysis and organ culture. We found evidence of melanocyte apoptosis and increased oxidative stress in the pigmentary unit of graying hair follicles. The "common" deletion, a marker mitochondrial DNA-deletion for accumulating oxidative stress damage, occurred most prominently in graying hair follicles. Cultured unpigmented hair follicles grew better than pigmented follicles of the same donors. Finally, cultured pigmented hair follicles exposed to exogenous oxidative stress (hydroquinone) showed increased melanocyte apoptosis in the hair bulb. We conclude that oxidative stress is high in hair follicle melanocytes and leads to their selective premature aging and apoptosis. The graying hair follicle, therefore, offers a unique model system to study oxidative stress and aging and to test antiaging therapeutics in their ability to slow down or even stop this process.

Dietary flavonoids advance timing of moult but do not affect redox status of juvenile blackbirds (Turdus merula)

“…Adult blackbirds express a eumelanin-based black (males) or dark grey/brown (females) plumage (McGraw, 2006;Galván and Jorge, 2015), and previous evidence suggests significant links between dietary antioxidants and melanin biosynthesis (Catoni et al, 2009). By improving antioxidant defences, flavonoids may enhance melanocyte development (Bowers et al, 1994(Bowers et al, , 1999Arck et al, 2006). Flavonoids may also increase the bioavailability of calcium, a crucial element favouring melanin biosynthesis (e.g.…”

Premature Greying of Hair (Premature Canities): A Concern for Parent and Child

“…The hair bulb tyrosinase activity gradually peaks at middle age and the bulbs of grey or white hairs appear to lack or be deficient in tyrosinase [8]. Repetitive oxidative stress causes apoptosis of hair follicle melanocytes, resulting in normal hair greying and premature greying is related to exhaustion and poor sustenance of the melanocyte stem cell pool [9]. The genes Pax-3 and MITE play an important role in melanocyte stem cell maintenance and differentiation [10].…”

“…However, among grey or white hairs, there may be a few normal bulbs producing dark hairs [8]. In grey hair, the pigmentary unit becomes fuzzy, melanocytes are few and rounded, and lightly pigmented oligodendritic melanocytes become detectable in the proximal hair bulb below Auber's line [9]. The resultant pigment loss in greying hair follicles due to a marked reduction in melanogenically active melanocytes in the hair bulb of grey anagen hair follicles is central to the pathogenesis of greying [12].…”

Stem cell factor/c-Kit signalling in normal and androgenetic alopecia hair follicles

“…These could be a stem cell reservoir for the bulb, to enable melanin production to continue throughout the very long anagen of human scalp hair; less differentiated melanocytes were detected in the lower bulb rim after dermabrasion (Staricco 1960). Since melanin synthesis produces damaging oxidative stress (Arck et al 2006) replacement melanocytes may be necessary to maintain the pigment. Such less differentiated cells could also be the few melanocytes that persist after anagen, moving upwards in catagen to the telogen capsule and possibly populating the next anagen bulb (Commo & Bernard 2000, Sharov et al 2005.…”