Your Trusted Brand for Over 35 Years

Life Extension Magazine

<< Back to April 2017

Mediterranean diet, Geroprotectors, Metformin, and Skin pigmentation

April 2017

Skin pigmentation

Mechanisms regulating skin pigmentation: the rise and fall of complexion coloration.

Skin pigmentary abnormalities are seen as aesthetically unfavorable and have led to the development of cosmetic and therapeutic treatment modalities of varying efficacy. Hence, several putative depigmenting agents aimed at modulating skin pigmentation are currently being researched or sold in commercially available products. In this review we will discuss the regulation of processes that control skin complexion coloration. This includes direct inhibition of tyrosinase and related melanogenic enzymes, regulation of melanocyte homeostasis, alteration of constitutive and facultative pigmentation and down-regulation of melanosome transfer to the keratinocytes. These various processes, in the complex mechanism of skin pigmentation, can be regulated individually or concomitantly to alter complexion coloration and thus ameliorate skin complexion diseases.

Int J Mol Sci. 2009 Sep 15;10(9):4066-87

Quasi-drugs developed in Japan for the prevention or treatment of hyperpigmentary disorders.

Excess production of melanin or its abnormal distribution, or both, can cause irregular hyperpigmentation of the skin, leading to melasma and age spots. To date, various quasi-drugs that prevent or improve hyperpigmentary disorders have been developed and officially approved by the Ministry of Health, Labor and Welfare of Japan. Many of these inhibit the activity of tyrosinase, an enzyme required for melanin synthesis, for example, by competitive or non-competitive inhibition of its catalytic activity, by inhibiting its maturation, or by accelerating its degradation. In this review, we categorize the quasi-drugs developed in Japan to prevent or treat hyperpigmentary disorders, or both, and discuss perspectives for future development.

Int J Mol Sci. 2010 Jun 18;11(6):2566-75

The protective role of melanin against UV damage in human skin.

Human skin is repeatedly exposed to UVR that influences the function and survival of many cell types and is regarded as the main causative factor in the induction of skin cancer. It has been traditionally believed that skin pigmentation is the most important photoprotective factor, as melanin, besides functioning as a broadband UV absorbent, has antioxidant and radical scavenging properties. Besides, many epidemiological studies have shown a lower incidence for skin cancer in individuals with darker skin compared to those with fair skin. Skin pigmentation is of great cultural and cosmetic importance, yet the role of melanin in photoprotection is still controversial. This article outlines the major acute and chronic effects of UVR on human skin, the properties of melanin, the regulation of pigmentation and its effect on skin cancer prevention.

Photochem Photobiol. 2008 May-J

Shining light on skin pigmentation: the darker and the brighter side of effects of UV radiation.

The term barrier function as applied to human skin often connotes the physical properties of this organ that provides protection from its surrounding environment. This term does not generally include skin pigmentation. However, skin pigmentation, which is the result of melanin produced in melanocytes residing in the basal layer of the skin and exported to the keratinocytes in the upper layers, serves equally important protective function. Indeed, changes in skin pigmentation are often the most readily recognized indicators of exposure of skin to damaging agents, especially to natural and artificial radiation in the environment. Several recent studies have shed new light on (1) the mechanisms involved in selective effects of subcomponents of UV radiation on human skin pigmentation and (2) the interactive influences between keratinocytes and melanocytes, acting as "epidermal melanin unit," that manifest as changes in skin pigmentation in response to exposure to various forms of radiation. This article provides a concise review of our current understanding of the effects of the nonionizing solar radiation, at cellular and molecular levels, on human skin pigmentation.

Photochem Photobiol. 2012 Sep-Oct;88(5): 1075-82

Hyperpigmentation and melasma.

Facial and neck pigmentations are significant cosmetic problems. They are common in middle-aged women, related to endogenous (hormones) and exogenous factors (cosmetics, perfumes, sun exposure), and often represent paramount causes of emotional distress. Although melasma is the most common cause of facial pigmentation, there are many other forms including drug-induced and postinflammatory hyperpigmentation. We review pathogenesis, clinical and histopathological data, effect on quality of life, and treatment options in facial hyperpigmentation disorders.

J Cosmet Dermatol. 2007 Sep;6(3):195-202

Cellular mechanisms regulating human melanogenesis.

The major differentiated function of melanocytes is the synthesis of melanin, a pigmented heteropolymer that is synthesized in specialized cellular organelles termed melanosomes. Mature melanosomes are transferred to neighboring keratinocytes and are arranged in a supranuclear cap, protecting the DNA against incident ultraviolet light (UV) irradiation. The synthesis and distribution of melanin in the epidermis involves several steps: transcription of melanogenic proteins, melanosome biogenesis, sorting of melanogenic proteins into the melanosomes, transport of melanosomes to the tips of melanocyte dendrites and finally transfer into keratinocytes. These events are tightly regulated by a variety of paracrine and autocrine factors in response to endogenous and exogenous stimuli, principally UV irradiation.

Cell Mol Life Sci. 2009 May;66(9):1493-506

The melanocortin-1 receptor is a key regulator of human cutaneous pigmentation.

The cloning and characterization of the human melanocortin-1 receptor (MC1R) and the demonstration that normal human melanocytes respond to the melanocortins, alpha-melanocyte stimulating hormone (alpha-MSH) and adrenocorticotrophic hormone (ACTH), with increased proliferation and eumelanogenesis had put an end to a long-standing controversy about the role of melanocortins in regulating human cutaneous pigmentation. We have shown that alpha-MSH and ACTH bind the human MC1R with equal affinity, and are equipotent in their mitogenic and melanogenic effects on human melanocytes. We also showed that the activation of the MC1R is important for the melanogenic response of human melanocytes to ultraviolet radiation (UVR). The MC1R is also the principal mediator of the inhibitory effects of agouti signaling protein (ASP) on melanogenesis. Expression of the MC1R is subject to regulation by its own ligands alpha-MSH and ACTH, as well as by UVR and endothelin-1. Recent studies that we conducted on the expression of MC1R variants by human melanocytes and the implications of these variants on the function of the MC1R revealed the following. Human melanocytes homozygous for Arg160Trp mutation in the MC1R demonstrated a significantly reduced response to alpha-MSH. Also, this culture responded poorly to ASP and exhibited an exaggerated cytotoxic response to UVR. Another culture, which was homozygous for Val92Met mutation in the MC1R, demonstrated a normal response to alpha-MSH. Heterozygous mutations that are frequently expressed in various melanocyte cultures did not disrupt MC1R function. These results begin to elucidate the significance of MC1R variants in the function of the receptor. Our data emphasize the significance of a normally functioning MC1R in the response of melanocytes to melanocortins, ASP, and UVR.

Pigment Cell Res. 2000;13 Suppl 8:156-62

Melasma update.

Melasma is an acquired pigmentary disorder characterized by symmetrical hyperpigmented macules on the face. Its pathogenesis is complex and involves the interplay of various factors such as genetic predisposition, ultraviolet radiation, hormonal factors, and drugs. An insight into the pathogenesis is important to devise treatment modalities that accurately target the disease process and prevent relapses. Hydroquinone remains the gold standard of treatment though many newer drugs, especially plant extracts, have been developed in the last few years. In this article, we review the pathogenetic factors involved in melasma. We also describe the newer treatment options available and their efficacy. We carried out a PubMed search using the following terms "melasma, pathogenesis, etiology, diagnosis, treatment" and have included data of the last few years.

Indian Dermatol Online J. 2014 Oct;5(4):426-35