Molecular and histological characterization of age spots

Abstract

Age spots, also called solar lentigines and lentigo senilis, are light brown to black pigmented lesions of various sizes that typically develop in chronically sun-exposed skin. It is well known that age spots are strongly related to chronic sun exposure and are associated with photodamage and an increased risk for skin cancer, however, the mechanism(s) underlying their development remain poorly understood. We used immunohistochemical analysis and microarray analysis to investigate the processes involved in their formation, focusing on specific markers associated with the functions and proliferation of melanocytes and keratinocytes. A total of 193 genes were differentially expressed in age spots but melanocyte pigment genes were not among them. The increased expression of keratins 5 and 10, markers of basal and suprabasal keratinocytes, respectively, in age spots suggests that the increased proliferation of basal keratinocytes combined with the decreased turnover of suprabasal keratinocytes leads to the exaggerated formation of rete ridges in lesional epidermis which in turn disrupts the normal processing of melanin upwards from the basal layer. Based on our results, we propose a model for the development of age spots that explains the accumulation of melanin and the development of extensive rete ridges in those hyperpigmented lesions.

Bio‐derived hydroxystearic acid ameliorates skin age spots and conspicuous pores

“…HSA was shown to reduce the negative effects of UV irradiation on the epidermis in vitro (reduced SBC formation and p53 levels). These effects are consistent with an improvement in keratinocyte differentiation capacity and will help with the poor keratinization of keratinocytes in age spots and the surrounding epidermis around skin pores . Furthermore, HSA was also shown to increase collagen type I and III synthesis and reduce MMP levels, which will help to improve the pilosebaceous pore wall slackening in conspicuous skin pores.…”

“…Both skin problems are induced by oxidative stress to the skin and have some similarities in their pathophysiology. Poor keratinocyte differentiation and aberrations to the DEJ are characteristic to both . As a result, agents that improve epidermal differentiation or reduce the negative effects of UV irradiation on keratinocyte differentiation are likely to be beneficial.…”

“…Downregulation of genes involved in epidermal differentiation has also been reported in age spots as well as decreased expression of filaggrin and involucrin . Increased expression of the basal type keratins 5 and 10 also indicates poor keratinocyte differentiation in age spots . Increased p53 levels also contribute to defective epidermal differentiation .…”

“…Increased p53 levels also contribute to defective epidermal differentiation . The most recent hypothesis is that the increased proliferation of basal keratinocytes combined with decreased turnover of suprabasal keratinocytes puts a backward pressure on the DEJ leading to an exaggerated formation of rete ridges, similar to that in age spots, which also leads to reduced melanin processing upwards from the basal layer of the epidermis . The poor turnover of the suprabasal cells is also suggested by increased numbers of cell layers in the stratum corneum in age spots.…”

Focus Theme Issue: “Vitiligo and other pigmentary disorders”

“…Two papers concerning the increasingly important topic of epigenetics of pigmentation are also featured: Takaaki Yamada and colleagues, from Fujita Health University, Toyoake, Japan, suggest that, in skin exposed to a high amount of UV irradiation, demethylation of the WNT1 promoter induces melanocytogenesis and melanogenesis resulting in the formation of solar lentigines . This study adds a potential new pathomechanism to the study of age spots . Chuhan Fu and colleagues, from Changsha, China, studied taurine‐upregulated gene 1 (TUG1), a long non‐coding RNA family, which is already known to be involved in the regulation of cell growth, cancer, insulin secretion, yet remains to be studied in melanogenesis.…”