Dr. Philip Frost Department for Dermatology and Cutaneous Surgery, University of Miami, Miami, Florida, 33136, U.S.A.
Departments of Psychiatry and Neurology, Columbia University Irving Medical Center, 622 W 168th Street, PH1540N, New York, 10032, U.S.A.
Biol Rev Camb Philos Soc. 2021 Feb;96(1):107-128. doi: 10.1111/brv.12648. Epub 2020 Sep 23.
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.
头发变白（灰发）是最早出现的、最明显的与衰老相关的现象之一，其受遗传、心理情绪、氧化、衰老相关、代谢和营养因素的调节一直吸引着皮肤生物学家、皮肤科医生和行业的关注。在人口老龄化日益加剧的情况下，头发变白具有深远的心理和商业意义。此外，人类生长期毛囊色素单位（HFPU）中黑色素生成的缺陷开始和持续，为研究复杂人类小型器官的衰老分子机制提供了极好的模型，而毛球黑素细胞干细胞（MSC）中与白发相关的缺陷代表了神经嵴衍生干细胞衰老的一个有趣系统。在这里，我们强调人类白发的发生总是从黑色素生成的逐渐下降开始，包括酪氨酸酶活性降低、黑素小体转移缺陷和 HFPU 黑素细胞凋亡，因此这是生长期毛囊的主要事件，而不是毛球。最终，毛球 MSC 池也会耗尽，此时白发变得几乎不可逆转。目前仍然没有普遍接受的人类头发变白模型，遗传因素对白发的影响程度也不清楚。然而，氧化损伤可能是通过破坏 HFPU 黑素细胞存活、MSC 维持以及黑色素生成的酶系统，成为白发的关键驱动因素。虽然神经内分泌因子（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）、促甲状腺素释放激素（TRH））和小眼畸形相关转录因子（MITF）是众所周知的人类毛囊黑素细胞和黑色素生成的调节剂，但这些和其他因素（如甲状腺激素、肝细胞生长因子（HGF）、P-钙黏蛋白、外周时钟活动）如何确切地调节白发还需要更详细的研究。其他重要的悬而未决的问题包括 HFPU 黑素细胞如何内在衰老，心理情绪压力如何影响这个过程，以及目前对人类 HFPU 老年生物学的认识如何最好地转化为延缓或逆转白发。
