Abstract
Hair graying is the most obvious sign of aging in humans, yet its mechanism is largely unknown. Here, we used melanocyte-tagged transgenic mice and aging human hair follicles to demonstrate that hair graying is caused by defective self-maintenance of melanocyte stem cells. This process is accelerated dramatically with Bcl2 deficiency, which causes selective apoptosis of melanocyte stem cells, but not of differentiated melanocytes, within the niche at their entry into the dormant state. Furthermore, physiologic aging of melanocyte stem cells was associated with ectopic pigmentation or differentiation within the niche, a process accelerated by mutation of the melanocyte master transcriptional regulator Mitf.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adult
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Aged
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Aged, 80 and over
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Aging / physiology*
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Animals
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Apoptosis
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Cell Differentiation
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Cell Shape
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Hair Color*
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Hair Follicle / cytology
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Hair Follicle / physiology*
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Humans
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Melanins / biosynthesis
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Melanocytes / physiology*
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Microphthalmia-Associated Transcription Factor
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Middle Aged
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Morphogenesis
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-bcl-2
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Stem Cells / physiology*
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Vibrissae / cytology
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Vibrissae / physiology
Substances
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DNA-Binding Proteins
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MITF protein, human
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Melanins
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Microphthalmia-Associated Transcription Factor
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Mitf protein, mouse
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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Transcription Factors
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Bcl2 protein, mouse