The major compounds in the dermis are hyaluronan and type I collagen, which decrease with aging, UV and various other factors. The loss of hyaluronan and collagen with aging is associated with increased dehydration and wrinkling of the skin. We aimed to investigate the influence of hyaluronan tetrasaccharide (HA4) on regulation of high molecular weight hyaluronan (HA) and collagen synthesis in normal human dermal fibroblasts (NHDFs). Expression of hyaluronan synthase (HAS) 1–3 and collagen (COL) 1A1 mRNA were evaluated by quantitative real-time PCR. HAS1 mRNA expression was found to be increased in NHDFs treated with HA and HA4. In addition, it was observed that NHDFs co-cultured with normal human epidermal keratinocytes (NHEKs) showed up-regulation of HAS1 mRNA expression, as compared with NHDFs single cell culture treated with HA4. Treatment of NHDFs with HA4 + derivatized vitamin C (VC-PMg) significantly increased COL1A1 mRNA expression. In this study, we confirmed that HA4 affected HAS1 and COL1A1 mRNA expression; thus, HA4 application may show various action in skin.

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Skin aging following repeated exposures to ultraviolet (UV) irradiation and tobacco smoking results largely from the damage to cutaneous connective tissue, which is composed of collagen, elastin, and proteoglycans. The alterations of cellular component and the extracellular matrix of dermal connective tissue after exposure to UV and tobacco smoke extracts. Our findings indicated that the skin premature aging induced by UV and tobacco smoke extracts share molecular features including abnormal regulation of extracellular matrix deposition through elevated MMPs, reduced collagen production and abnormal proteoglycan accumulation via ROS generation. Tobacco smoke contains more than 3800 constituents, including numerous water insoluble polycyclic aromatic hydrocarbons that trigger the aryl hydrocarbon receptor (AhR; also called the dioxin receptor) signaling pathway. AhR knockdown abolished the increase in transcription of the AhR-dependent gene CYP1A1/CYP1B1 and MMP-1 upon treatment with either tobacco smoke extract. These findings suggest that the tobacco smoke extracts induced MMP-1 expression in human fibroblasts and keratinocytes via activation of the AhR pathway. Thus, the AhR pathway may be pathogenetically involved in extrinsic skin aging. In addition, natural sun light includes visible light and infrared A (IR-A). Although the effects of ultraviolet for photoaging have been largely investigated, those of IR-A remain unclear. Based on the recent studies, infrared A shares the mechanisms for photoaging with UV, including the induction of matrix metalloproteinase (MMP)-1 through ERK and p38 MAP kinase activation. IR-A is absorbed intramitochondrially. There might be a chromosphere for IR-A radiation.

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For the elder population, anti-aging is one of strong demand to maintain activity and quality of life. In general, aging is perceived by appearance changes in the face such as wrinkles, sagging and some pigment spots. One of causes expressing these changes is oxidative stress initiated by endogenous and exogenous reactive oxygen species (ROS). In environmental factors, the solar lights are a well-known generator of ROS and an accelerator of skin aging. ROS progresses some events such as DNA damage, up-regulations of MMP-1 and tyrosinase. Among anti-aging approaches, sunscreen products are a first defense against the solar lights, and antioxidants are also a defense against ROS. Estradiol is recognized to have abilities on skin rejuvenation exhibiting some risks of breast cancer potentially. In addition, vitamin A derivatives and triterpenoids are widely used in cosmetics as active materials. The relationship between these chemical structures and anti-aging efficacies were discussed to develop new materials for anti-aging in the skin. In the article, the skin aging mechanisms authorized by many previous investigations were summarized and some approaches corresponding to mechanisms were introduced citing papers.

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Wrinkles associated with aged and/or chronic sun-damaged skin are considered to be a significant cause of psychological distress. Apart from the aggravation of the structural integrity of the extracellular matrix, including the increased disintegration and/or reduction of elastins and collagens, which results in the loss of skin elasticity, it has been recently proposed that decreased flexibility or elasticity of the stratum corneum (SC) is also correlated with wrinkle formation. Especially in the wrinkle incidence correlated with sun damage, the aberrant expression of keratins 6 and 16 have been reported to deteriorate epidermal elasticity. In accordance with the finding that the elasticity of the SC is regulated, at least in part, by the amounts and types of amino acids, an amino acid-derivative (1-carbamimidoyl-L-proline; CLP), was newly developed which recovered their abnormal expressions and the elastic properties of the SC ex vivo, and a clinical test was performed with 126 Japanese female subjects aged 32–50 years who had crow's feet lines on the right side of their faces. According to authorized grades by the Japanese Cosmetic Science Society, three eligible dermatologists evaluated the subjects as much improved or improved in 29.7% and 57.8% of all CLP-treated subjects at 4 and 8 weeks, respectively. In contrast, only 1.5% and 8.1% of subjects were evaluated as improved with the placebo lotion at 4 and 8 weeks, respectively. In parallel with the dermatologists' assessments, skin surface roughness in the CLP-treated group was significantly reduced after treatment with CLP for 4 and 8 weeks compared to the placebo-treated group. The sum of these data suggests that CLP is a promising and useful ingredient for the improvement of wrinkles through its ability to enhance the elasticity of the SC.

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For the treatment of wrinkles, we used to operate patients. Recently we do more non-surgical treatments such as injections. I started to inject collagen since 1984. Patients need to have skin test for bovine collagen before the injection of this material. Three percent of the patients are positive to the bovine collagen. Hyaluronic acid, hydroxyl apatite, botulinum toxin are new products for the treatment of wrinkles. How to use these materials is very important. Characteristics of these injectable materials are different from each other and we have to know what material is good for a certain case.

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