Nishimura Emi K, Granter Scott R, Fisher David E
Department of Pediatric Hematology/Oncology, Melanoma Program in Medical Oncology, Dana-Farber Cancer Institute, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Science. 2005 Feb 4;307(5710):720-4. doi: 10.1126/science.1099593. Epub 2004 Dec 23.
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.
头发变白是人类衰老最明显的标志，但其机制在很大程度上尚不清楚。在这里，我们使用黑素细胞标记的转基因小鼠和衰老的人类毛囊来证明，头发变白是由黑素细胞干细胞自我维持缺陷引起的。随着Bcl2缺乏，这个过程会显著加速，Bcl2缺乏会导致黑素细胞干细胞在进入休眠状态时在其微环境内发生选择性凋亡，但不会导致分化的黑素细胞凋亡。此外，黑素细胞干细胞的生理性衰老与微环境内的异位色素沉着或分化有关，黑素细胞主要转录调节因子Mitf的突变会加速这一过程。
