Canities, physiological L67.1

Pyhsiological graying of the hair, also known as achromotrichia, occurs with the normal ageing process. However, the age at which it occurs varies between ethnic groups. A large population-based study found that 6% to 23% of people have 50% gray hair by the age of 50.

Premature graying is defined as hair graying before the age of 20 for Caucasians and before the age of 30 for darker-skinned ethnicities.

The average age for the onset of graying is 34 ± 9.6 years for Caucasians and 43.9 ± 10.3 years for dark-skinned people.

The color of human hair is due to the pigment melanin, which is produced by melanocytes located in the hair bulb.

The human hair follicle contains two types of melanin: eumelanin and pheomelanin. The variety of hair color results mainly from the amount and ratio of black-brown eumelanin and reddish-brown pheomelanin. The phenotype of the hair is influenced by the pH value and the cysteine content of the melanosomes. If the pH value falls, there is a progressive reduction in tyrosinase activity. This leads to an increase in pheomelanin and to reddish or blond hair.

A mutation in the melanocortin-1 receptor(MC1R) gene causes auburn or red hair color. This mutation usually occurs in people in northern Europe who are less exposed to the sun.

There are various differences between the pigmentation of the epidermis and the hair. In the hair bulb, each melanocyte is connected to five keratinocytes and forms a "hair follicle-melanin unit". In the skin, on the other hand, a melanocyte is connected to 36-40 keratinocytes and together with this network forms an "epidermis-melanin unit".

In contrast to the epidermis, where pigment production is continuous, melanogenesis in the hair is closely linked to the phases of the hair cycle. In the anagen phase the hair is actively pigmented, in the catagen phase melanogenesis is "reduced and switched off" and in the telogen phase it is completely absent.

In normally pigmented anagen hair, the active pigmentation unit is visible as a pear-shaped, black structure at the tip of the dermal papilla. In gray hair, this pigmentation unit becomes blurred, the number of melanocytes is reduced; they round off. Autophagolysosomal degeneration occurs. In the anagen phase, the number of melanocytes in the hair follicles decreases and the hair becomes lighter. It can be assumed that this process plays a central role in the pathogenesis of graying. Furthermore, inadequate transfer of melanosomes to cortical keratinocytes or melanin incontinence due to melanocyte degeneration appear to contribute to graying. Ultimately, the melanocytes disappear completely from the hair bulb.

In pigmented hairs, terminal differentiation takes place earlier than in non-pigmented hairs.

The growth rate, the medulla diameter and the average diameter of non-pigmented hairs are higher than those of pigmented hairs.

Genetic and environmental influences affect the hair follicle stem cells and melanocytes. The shortening of telomeres, the decrease in cell number and certain transcription factors are associated with this ageing process. These molecular changes in turn lead to structural changes in the hair fiber, reduced melanin production and an extension of the telogen phase of the hair cycle. At the molecular level, various genes and signaling pathways are known to influence hair pigmentation.

For example, it is known that the receptors Bmpr2 (see Bmpr2 gene below) and Acvr2a (see Acvr2a gene below) influence hair pigmentation. Animal experiments have shown that reduced activity of Bmpr2 and Acvr2 leads to early graying. The Notch signaling pathway also influences various biological processes in hair growth and pigmentation. Stem cell factor, a cytokine that is involved in many physiological processes such as hematopoiesis, also plays a role in melanogenesis together with its receptor (see KIT gene below) in the anagen phase of hair growth.

A melanocyte-specific deletion of BMI1 (see BMI-1 gene below) leads to premature graying of the hair and a gradual loss of cells of the melanocyte lineage in mice. Depilation exacerbates this hair graying defect and accelerates the loss of McSCs in early hair cycles, suggesting that BMI1 protects McSCs from stress. In addition, loss of BMI1 downregulated the glutathione S-transferase enzymes Gsta1 and Gsta2, which can suppress oxidative stress. Accordingly, treatment with the antioxidant N-acetylcysteine (NAC) partially restored melanocyte expansion (Wilson MM et al.2023).

1. Han R et al. (2012) Apair of transmembrane receptors essential for the retention and pigmentation of hair. Genesis 50:783-800.
2. Wang H et al. (2004) Role of histone H2A ubiquitination in Polycomb silencing. Nature 431:873-878.
3. Wilson MM et al.(2023) BMI1 is required for melanocyte stem cell maintenance and hair pigmentation. Pigment Cell Melanoma Res 36:399-406.