Hair greying (canities) is one of the earliest, most visible ageing‐associated phenomena, whose modulation by genetic, psychoemotional, oxidative, senescence‐associated, metabolic and nutritional factors has long attracted skin biologists, dermatologists, and industry. Greying is of profound psychological and commercial relevance in increasingly ageing populations. In addition, the onset and perpetuation of defective melanin production in the human anagen hair follicle pigmentary unit (HFPU) provides a superb model for interrogating the molecular mechanisms of ageing in a complex human mini‐organ, and greying‐associated defects in bulge melanocyte stem cells (MSCs) represent an intriguing system of neural crest‐derived stem cell senescence. Here, we emphasize that human greying invariably begins with the gradual decline in melanogenesis, including reduced tyrosinase activity, defective melanosome transfer and apoptosis of HFPU melanocytes, and is thus a primary event of the anagen hair bulb, not the bulge. Eventually, the bulge MSC pool becomes depleted as well, at which stage greying becomes largely irreversible. There is still no universally accepted model of human hair greying, and the extent of genetic contributions to greying remains unclear. However, oxidative damage likely is a crucial driver of greying via its disruption of HFPU melanocyte survival, MSC maintenance, and of the enzymatic apparatus of melanogenesis itself. While neuroendocrine factors [e.g. alpha melanocyte‐stimulating hormone (α‐MSH), adrenocorticotropic hormone (ACTH), ß‐endorphin, corticotropin‐releasing hormone (CRH), thyrotropin‐releasing hormone (TRH)], and micropthalmia‐associated transcription factor (MITF) are well‐known regulators of human hair follicle melanocytes and melanogenesis, how exactly these and other factors [e.g. thyroid hormones, hepatocyte growth factor (HGF), P‐cadherin, peripheral clock activity] modulate greying requires more detailed study. Other important open questions include how HFPU melanocytes age intrinsically, how psychoemotional stress impacts this process, and how current insights into the gerontobiology of the human HFPU can best be translated into retardation or reversal of greying.

中文翻译：

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人类头发变白的生物学

头发变白（canities）是最早、最明显的衰老相关现象之一，其受遗传、心理情绪、氧化、衰老相关、代谢和营养因素的调节长期以来一直吸引着皮肤生物学家、皮肤科医生和工业界。在日益老龄化的人口中，变灰具有深刻的心理和商业相关性。此外，人类生长期毛囊色素单元（HFPU）中黑色素产生缺陷的发生和持续，为研究复杂的人类微型器官衰老的分子机制和膨出黑素细胞干的灰色相关缺陷提供了极好的模型。细胞（MSCs）代表了一个有趣的神经嵴干细胞衰老系统。在这里，我们强调人类变白总是随着黑色素生成的逐渐减少而开始，包括酪氨酸酶活性降低、黑素体转移缺陷和 HFPU 黑素细胞凋亡，因此是生长期毛球的主要事件，而不是隆起。最终，膨胀的 MSC 池也会耗尽，在这个阶段，变灰在很大程度上变得不可逆转。仍然没有普遍接受的人类头发变白模型，并且遗传对变白的贡献程度仍不清楚。然而，氧化损伤可能是通过其对 HFPU 黑素细胞存活、MSC 维持和黑素生成本身的酶装置的破坏而导致变灰的关键驱动因素。而神经内分泌因子[例如α-黑色素细胞刺激素（α-MSH）、促肾上腺皮质激素（ACTH）、β-内啡肽、促肾上腺皮质激素释放激素（CRH）、促甲状腺激素释放激素（TRH）]，和小眼病相关转录因子 (MITF) 是众所周知的人类毛囊黑色素细胞和黑色素生成的调节剂，这些和其他因素 [例如甲状腺激素、肝细胞生长因子 (HGF)、P-钙粘蛋白、外周时钟活性] 究竟如何调节白发需要更详细的研究。其他重要的开放性问题包括 HFPU 黑素细胞本质上是如何老化的，心理情绪压力如何影响这个过程，以及目前对人类 HFPU 老年生物学的见解如何最好地转化为延缓或逆转变灰。