Current Understanding of the Role of Senescent Melanocytes in Skin Ageing

Abstract

Melanocytes reside within the basal epidermis of human skin, and function to protect the skin from ultraviolet light through the production of melanin. Prolonged exposure of the skin to UV light can induce irreparable DNA damage and drive cells into senescence, a sustained cell cycle arrest that prevents the propagation of this damage. Senescent cells can also be detrimental and contribute to skin ageing phenotypes through their senescence-associated secretory phenotype. Senescent cells can act in both an autocrine and paracrine manner to produce widespread tissue inflammation and skin ageing. Recently, melanocytes have been identified as the main senescent cell population within the epidermis and have been linked to a variety of skin ageing phenotypes, such as epidermal thinning and the presence of wrinkles. However, the literature surrounding melanocyte senescence is limited and tends to focus on the role of senescence in the prevention of melanoma. Therefore, this review aims to explore the current understanding of the contribution of senescent melanocytes to human skin ageing.

Keywords: UV; ageing; melanocyte; senescence; skin.

Figure 1

Eumelanin and pheomelanin production. Adapted from Cichorek et al., 2013 [5]. Tyrosine is converted to levodopa (L-DOPA) and dopaquinone by the enzyme tyrosinase. Here, the pathway diverges dependent on the presence of cysteine to form either brown/black eumelanins or yellow/red phenomelanins. During eumelanin production, dopachrome can be converted to 5,6-dihydroxyindole-2-carboxylic acid (DHICA) melanin, facilitated by the presence of tyrosinase-related proteins 1 and 2 (TRP1 and TRP2). To form pheomelanin, cysteinylDOPA is oxidised.

Figure 2

The structure of young versus old skin. (A) Human skin is divided into an epidermis, dermis, and subcutaneous adipose tissue. The epidermis contains stratified layers of keratinocytes, and melanocytes within the basal layer. The dermis is further divided into a fibroblast-rich papillary layer, and an ECM-rich reticular layer containing collagens and elastin. (B) With age, the epidermis may become thinner (intrinsic ageing) or thicker (extrinsic ageing), the stratum corneum barrier becomes dysfunctional, and there is the presence of senescent melanocytes within the basal layer. The dermal matrix becomes disorganised, with a loss of collagen and changes in elastin content, and an accumulation of senescent fibroblasts. There is also a loss of adipose tissue.