Photoaging of the skin46 Solar radiation at the surface of the earth includes ultraviolet radiation (UV : 290-400nm), visible light (400-760nm) and infrared radiation (760nm-1mm) (Fig 1).Extrinsic skin aging is superimposed on intrinsic skin aging process and is due primarily to UVR (solar ultraviolet radiation) and partly by other factors, such as infrared light, smoking and air pollutants. UVR has been divided into ultraviolet B (UVB: 290-320nm) which principally generates pyrimidine dimer type DNA damage through direct absorption and ultraviolet A (UVA: 320-400nm), which indirectly produces base oxidation via UVinduced ROS.Recently , UVA radiation at high dose is reported to produce cyclobutane pyrimidine dimmers.Intrinsic aging of the skin, on the other hand, is characterized by the decline of biological function, a decrease in adaptation to stress, and structural damage due to reactive oxygen species (ROS) from cellular metabolism.Recent advances in understanding mechanisms of aging and photoaging have enhanced our ability to develop strategies to prevent, slow, and rejuvenate the altered structure and function of photoaged skin.In this review, we discuss the mechanisms of photoaging of the skin with relevance to acute and chronic skin reactions to solar UVB, UVA and infrared radiation, and summarize briefly the clinical approaches for prevention and the treatment of photoaging with topical and systemic use of anti-aging materials. Finally, a range of therapeutic modalities available to reverse or retard the visible signs of photoaged skin will be discussed briefly. There are three lights with different waveband, infrared light (IR) having waveband between 760nm and 1mm, visible light (VL) from 400nm to 760nm, and ultraviolet light (UV) from 290nm to 400nm. IR, VL and UV occupy 42 %, 52 % and 6 % of the solar light on the earth, respectively. UV light is divided into two types according to waveband, UVA having waveband between 320nm and 400nm and UVB from 290nm to 320nm. Sunburn, acute skin reaction is caused predominantly by UVB which occupies only 5~6 % of total UV light. UVA radiation, however, penetrates deeply into the dermis, around 20 % of the surface of the skin.

Hyperpigmentation frequently accompanies chronic or acute inflammation. A number of inflammatory mediators have been shown to stimulate melanin synthesis in human melanocytes. Although histamine is ubiquitous as an inflammatory factor, its involvement in pigmentation remains obscure. In this work, we examined the effects of histamine on cultured human melanocytes. Treatment of human melanocytes with 0.1-10 microM histamine evoked morphologic changes and increases in tyrosinase activity. The concomitant increases in melanin content of the histamine-treated melanocytes indicated an elevation of melanin synthesis by tyrosinase activation. These stimulatory effects of histamine were completely inhibited by an H2 antagonist, famotidine, whereas H1 and H3 antagonists had no inhibitory effect whatsoever. In addition, an H2 agonist, dimaprit, induced the same degree of melanogenesis as histamine at concentrations of 0.1-10 microM. We observed an increase in the intracellular cAMP contents of human melanocytes induced by histamine via the H2 receptors. We know that this cAMP accumulation and subsequent protein kinase A activation plays a critical role in histamine-induced melanogenesis, because a specific protein kinase A inhibitor, H-89, completely suppressed these stimulatory effects of histamine, and because dibutylic cAMP, a specific protein kinase A activator, stimulated human melanocytes as potently as histamine. Taken together, we show here that histamine induces melanogenesis of human cultured melanocytes by protein kinase A activation via H2 receptors.

Photodamaged skin exhibits wrinkles, pigmented spots, dryness and tumors. Solar UV radiation induces cyclobutane pyrimidine dimers (CPD) and further produces base oxidation by reactive oxygen species (ROS). ROS are thought to be a major factor to initiate the up-regulation of matrix metalloproteinases (MMPs) in keratinocytes and fibroblasts via activation of receptor proteins on the cell membrane of keratinocytes and fibroblasts, and to degrade fiber components in dermis, leading to wrinkle formation. Coenzyme Q10 (CoQ10) was reported to reduce ROS production and DNA damage triggered by UVA irradiation in human keratinocytes in vitro. Further, CoQ10 was shown to reduce UVA-induced MMPs in cultured human dermal fibroblasts. We speculated that UVB radiation-induced cytokine production in keratinocytes may be inhibited by CoQ10, resulting in the reduction of MMPs in fibroblasts leading to wrinkle reduction. Our in vitro studies showed that UVB-induced IL-6 production of normal human keratinocyte (NHKC) decreased in the presence of CoQ10. Furthermore, MMP-1 production of fibroblasts cultured with the medium containing CoQ10 collected from UVB-irradiated NHKC significantly decreased during 24 h culture. In the clinical trial study, we found that the use of 1% CoQ10 cream for five months reduced wrinkle score grade observed by a dermatologist. Taken together, our results indicate that CoQ10 may inhibit the production of IL-6 which stimulate fibroblasts in dermis by paracrine manner to up-regulate MMPs production, and contribute to protecting dermal fiber components from degradation, leading to rejuvenation of wrinkled skin.

The mechanism of melanosome transfer from melanocytes to keratinocytes has not been fully clarified. We now show a route of melanosome transfer using co-cultures of normal human melanocytes and keratinocytes. Substantial levels of melanosome transfer were elicited in co-cultures of melanocytes and keratinocytes separated by a microporous membrane filter. The melanocyte dendrites penetrated into the keratinocyte layer through the filter and many pigment globules were observed in keratinocytes. Electron microscopic observations revealed that melanosomes incorporated in keratinocytes were packed in clusters enclosed by a double membrane. Numerous pigment globules budded off from melanocyte dendrites and were released into the culture medium. Those pigment globules were filled with multiple melanosomes and a few mitochondria but no nuclei. When those globules were added to the culture medium of keratinocytes, they were incorporated and showed double membrane-enclosed melano-phagolysosomes consistent with the structures obtained from the co-culture system. In contrast, when individual naked melanosomes isolated from melanocytes were added to keratinocytes, they were also phagocytosed by keratinocytes but were enclosed by a single membrane in a manner distinct from the co-culture system. These results suggest a novel mechanism of melanosome transfer, wherein melanosomes are packed in membrane globules that bud off from melanocyte dendrites, where they are released into the extracellular space and then phagocytosed by keratinocytes.