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FOR IMMEDIATE RELEASE Kanebo Cosmetics reveals new findings on photo-aging induced by UVA 1. Elastin in the lower dermis deteriorates during the early stage of photo-aging. 2. New photo-aging marker “COMP” detected. Tokyo, Japan – December 4, 2012 In a joint study on skin aging caused by ultraviolet (UV) rays, the Innovative Beauty Science Laboratory of Kanebo Cosmetics, in collaboration with the Departments of Dermatology, Plastic Surgery, and Cell Biology of Tokai University School of Medicine, succeeded in establishing a method of evaluation based on “photoaging histological stage,” which provides an objective index for evaluating the degree of progress of dermal tissue changes caused by photo-aging. It was also shown that photo-aging histological stage is significantly inter-correlated with visual evaluation of wrinkle scores. Furthermore, in the process of developing the index, researchers revealed for the first time that elastin abnormality develops in the lower dermis during the early stage of photo-aging. In the first part of this research project it was also discovered that the level of “COMP” (cartilage oligomeric matrix protein), a protein that stimulates collagen formation, is increased with the progress of photo-aging. Thus, it is considered that COMP is a unique marker for identifying damage related to photo-aging . Kanebo Cosmetics is promoting the development of products that effectively block UVA exposure and respond to photo-aging. The present findings, which clarified the progression of skin photo-aging by objective evaluation, are an important step in this direction. These results again demonstrated the significant effect of UVA on photo-aging. These results will be presented at the 37th Annual Meeting of the Japanese Society for Investigative Dermatology held in Naha, December 7-9 . What is photo-aging? Aging is caused by not only physiological factors (natural aging), but also environmental factors. Of all the various effectors, UV irradiation exerts the greatest effects on skin as it accelerates the progress of natural aging, and causes serious dark spots and winkles. For this reason, aging that progresses with long-term UV exposure is specifically referred to as ‘photo-aging’. With photo-aging, the skin becomes dull, mainly because of increased dark spots, and forms deep winkles due to decreased skin elasticity and firmness. It is known that marked damage such as deterioration of collagen and elastin develops in the inner skin, especially in the dermis. However, it has not been clarified where in the dermis the damage develops or how those changes progress. With this background in mind, the research group of Tokai University and Kanebo Cosmetics developed an index to show gradual changes in tissues, for the purpose of investigating the relationship between the effect of UV irradiation on skin and changes in dermal tissue. Relationship between progress of damage in dermal components and photo-aging histological stage The research group has been closely studying the histological structure of photoaged skin from various viewpoints. After a simultaneous evaluation of the dermal components elastin, collagen, and decorin (a molecule that regulates the diameter of collagen fibers and the distance between the fibers), the researchers were able to classify the degree of degeneration of the dermis extracellular matrix into 6 stages. That evaluation system was termed ‘photo-aging histological stage’ and used to establish an index for the progress of dermal tissue changes caused by photo-aging. With this index, extracellular matrix changes caused by UV irradiation can be objectively evaluated. Photo-aging histological stage (excerpt) Reddish purple: collagen Black: elastin Purple: decorin Progress of histological changes Stage I (mild) ~ Stage IV (severe) Stage I (mild) Stage III Stage VI (severe) Degeneration of elastin in lower dermis confirmed during early stage of photoaging In the process of establishing photo-aging histological stage, the research group looked into the origin of histological changes in the dermis. As a result, in photoaged skin, it was visually confirmed for the first time that elastin deteriorates in the lower dermis during the early stage. UV rays that reach earth are divided into two types, namely UVA and UVB. Those that easily reach the lower dermis because of their long wavelength are UVA rays. UVA radiation is considered to play a significant role in the development of photo-aging, thus our findings again showed that protection against both UVB and UVA is important to maintain beautiful skin. Epidermis Dermis An abnormal increase in elastin (dark-stained part in B, inside dotted line) was observed in the lower Skin unaffected by UV irradiation Skin in early photo-aging stage Noticeable wrinkles with advancement of photo-aging histological stage To investigate the relationship between photo-aging histological stage and skin appearance, the skin of 26 female subjects was analyzed. A correlation was found between photo-aging histological stage and wrinkle score, which revealed that the scores for wrinkles in the corners of the eyes, and clarity and depth of wrinkles were higher in skin in an advanced stage. These findings confirmed that deterioration of collagen, elastin, and decorin is significantly involved in the formation of wrinkles. Detection of photo-aging marker COMP To clarify the mechanism of skin photo-aging, the research group searched for factors greatly affected by UV irradiation in human skin. Those results revealed the importance of COMP (cartilage oligomeric matrix protein), a kind of protein that stimulates collagen formation, in photo-aged skin. Using photo-aging histological stage for evaluation, it was clarified that COMP emerged notably in skin with advanced photo-aging. To search for the mechanism of COMP emergence in photo-aged skin, dermal fibroblasts were exposed to UV rays. Those results showed that COMP synthesis was markedly increased not by UVB, but by UVA irradiation. Based on these findings, it is considered likely that COMP can be utilized as a marker to determine photo-aging damage accelerated by UVA. Studies of COMP will continue in the future. Skin not easily exposed to UV。 Skin easily exposed to UV [] COMP: red 200C COMP mRNA levels COMP mRNA increase induced by UVA irradiation Distribution of COMP in photo-aged skin 10 8 6 4 2 0 0 1.2 2.5 UVA (J/cm2) Kanebo Cosmetics, in collaboration with Tokai University, succeeded in objectively clarifying photo-aging progression using photo-aging histological stages. The results confirmed that the effect of UVA on photo-aging is not negligible. From these findings, the company will conduct further studies to clarify the mechanism that causes photo-aging in skin, and promote development of products that effectively protect against UVA and counteract photo-aging. Results obtained in the present study will be presented in the 37th Annual Meeting of the Japanese Society for Investigative Dermatology held in Naha, December 7-9. ### 5