Pos ranslational modifications, particularly cross-linking, are believed to be important in modulating the tissue-specific properties of type I collagens. The present findings support a concept that the 3Hyp collagen modification developed its substrate specificity during vertebrate evolution and contributed fundamentally to collagen fibril structure and the diversification of connective tissues. A recent worldwide survey showed that 74% of people between the ages of 45 and 65 have grey hair, and that occurs earliest in people of Caucasian descent, followed by Asians and Africans. Hair is considered to grey prematurely only if it occurs before the age of 20 years in Whites, before 25 years in Asians and before 30 years in Africans. Prematurely graying hair imposes a psychosocial burden on sufferers since it is often regarded as a visible sign of rapidly progressing old age, ill health and bodily decline. In spite of the fact that the onset of hair graying is genetically controlled and inheritable, there is very li le known about the mechanism by which functional melanocytes are lost from anagen graying hair follicles. Emerging evidence shows that reactive oxygen species accumulate in human gray/white scalp hair follicles up to millimolar concentrations, which likely causes oxidative damage to hair follicle melanocytes. Mature melanocytes are densely distributed in hair bulbs to sustain active melanogenesis that is Saikosaponin-B2 strictly coupled to the anagen stage of the hair cycle. Thus far, the precise mechanism governing the synchrony of hair growth and melanin synthesis has remained largely unclear. Isolation and short-term co-culture of primary keratinocytes, melanocytes and dermal papilla fibroblasts derived from human scalp skin tissues are common strategies to dissect the regulation of anagen-coupled melanogenesis. Unfortunately, in vitro co-culture studies with established cell lines or primary cell cultures could have led to artificial outcomes and some inaccuracies in earlier studies since hair follicles are Campesterol composed of several types of cells that span the range of differentiation states, for which it is considered a dynamic miniorgan. Graying hair offers a unique opportunity to study the uncoupling of melanin production with growth of the hair shaft. Although deficient antioxidant activity was reported in human graying hair follicles,, it remains to be determined whether an impaired antioxidant defense in gray hair follicles simultaneously affects mature hair bulb melanocytes and their immature precursor cells in the bulge region, which would have a critical implication for restoring pigmentation to 
the affected gray hair. In this study, we micro-dissected hair bulbs and mid-segments from unpigmented and from pigmented hair follicles isolated from the same human donors. The expression levels of genes encoding characteristic markers for mature melanocytes, melanocyte stem cells and keratinocyte stem cells in the hair bulbs and mid-segments were analyzed using quantitative real-time PCR arrays and the antioxidative properties of these segmented hair follicle tissues was investigated in parallel using a range of techniques. The results demonstrate that both mature hair bulb melanocytes and immature melanocyte precursor cells in the bulge region of gray hair follicles.