In our series of studies, the changes in the skin characteristics of mice caused by aging were investigated in correlation with the stem cells for keratinocytes and melanocytes in the natural hair cycle until middle age. The aim of the present review was to investigate these characteristics of hair follicles (HFs) at older age and complete the analysis of these changes as a study throughout the mouse lifetime. In addition, stem cells for keratinocytes and melanocytes were evaluated for changes in skin characteristics caused by aging. Postnatal day 200 (P200) appears to be the age of complete maturation of skin and the onset of aging with regard to HFs. Keratin 15-positive keratinocyte stem cells complete their localization as a quantitatively sufficient amount of progenitor in the hair bulge region and orchestrate the regeneration of hairs in every anagen phase thereafter. Although their frequency is low, an unusual structure of HFs, curved HFs, appear for the first time at P200. Thereafter, abnormal hair curvature continues to increase throughout life. In contrast, HF characteristics derived from melanocytes begin to show a high frequency of hypopigmented hair bulbs at P200 and appear to lead to a significant increase in the number of white hairs. Curved HFs and white hairs were considered biomarkers of aging in mice. The number of tyrosinase-related protein 2-positive melanocyte stem cells in the hair bulge is extremely low and may be one cause underlying not only the induction of melanocyte-derived characteristics by aging but possibly also that of keratinocyte-derived characteristics. These results provide insight into the mechanisms of the actions of stem cells on hair regeneration through the aging process.

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