Hair thinning and loss are prominent aging phenotypes but have an unknown mechanism. We show that hair follicle stem cell (HFSC) aging causes the stepwise miniaturization of hair follicles and eventual hair loss in wild-type mice and in humans. In vivo fate analysis of HFSCs revealed that the DNA damage response in HFSCs causes proteolysis of type XVII collagen (COL17A1/BP180), a critical molecule for HFSC maintenance, to trigger HFSC aging, characterized by the loss of stemness signatures and by epidermal commitment. Aged HFSCs are cyclically eliminated from the skin through terminal epidermal differentiation, thereby causing hair follicle miniaturization. The aging process can be recapitulated by Col17a1 deficiency and prevented by the forced maintenance of COL17A1 in HFSCs, demonstrating that COL17A1 in HFSCs orchestrates the stem cell-centric aging program of the epithelial mini-organ.
In order to gain a deeper insight into the role of 5 alpha-reductase in the growth of beards in men, we studied some kinetic properties of the enzyme in cell homogenates of cultured human dermal papilla cells from beard and occipital scalp hair. When cell homogenates were incubated with [3H]-testosterone, the 5 alpha-reductase of beard dermal papilla cells exhibited an optimum activity at pH 5.5, whereas the enzyme of dermal papilla cells from occipital scalp hair showed a broad and low plateau between pH 6.0 and 9.0, without a sharp peak. The apparent Michaelis constant of 5 alpha-reductase was 3.3 x 10(-7) M in dermal papilla cells from beard and 2.4 x 10(-5) M in those cells from occipital scalp hair. The apparent Km of 5 alpha-reductase for NADPH was 2.8 x 10(-5) M and 7.6 x 10(-4) M in beard and occipital scalp hair dermal papilla cells, respectively. There were no significant differences in the substrate specificity between these two types of cells. The 5 alpha-reductase activity was recovered mainly in the nuclear fraction of beard dermal papilla cells. By contrast, it was widely distributed among the individual subcellular fractions of dermal papilla cells from occipital scalp hair. These results strongly suggest that these two kinds of dermal papilla cells have different types of 5 alpha-reductase, and that the enzyme in beard dermal papilla cells is similar in characteristics to that in the androgen target organs such as prostate.
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