Ultraviolet rays (UV) cause premature wrinkle and sagging skin, which is called photoaging, through damage on human skin tissues and cells. Plasma membranes play an essential role in receiving extracellular signals and nutrients through membrane receptors and endocytotic membrane traffic events. Although damage on plasma membranes via membrane lipid peroxidation by UV was already reported, the relationship between photoaging and plasma membranes is still not fully understood. In this study, we investigated the relationship between functions of plasma membranes and collagen metabolism in UV-irradiated human dermal fibroblasts. The aim of this study is to clarify a part of relationship between wrinkle formation in photoaging and plasma membrane function in dermal fibroblasts. As a result, an irregular staining of plasma membranes by DiI, a reduction in neutral red (NR) uptake and a loss of membrane cholesterol were observed after UVA irradiation, while no changes were observed after UVB irradiation. The irregular DiI staining of plasma membranes and the reduction in NR uptake were also observed after Methyl-β-Cyclodextrin (MβCD) treatment which removes cholesterol from cell membranes. In addition, MβCD significantly decreased type I collagen mRNA expression and increased matrix metalloproteinase-1 mRNA expression in fibroblasts. These results suggest that UVA irradiation reduces plasma membrane cholesterol, alters plasma membrane behavior, and reduces the amount of collagen through changing a balance of collagen synthesis and degradation in dermal fibroblasts. Since a decrease in collagen causes wrinkle in photoaging skin, the loss of membrane cholesterol caused by UVA irradiation may be one of the causes of alterations observed in photoaging skin.

It is well known that excess sun UV exposure accelerates skin damage and aging. However, there are few studies to understand the impact on the skin aging under mild daily sun exposure in general life style such as office workers and/or housekeeping wives. Also, it is not well understood the longitudinal progression of chronic skin aging and its variation of individuals. Two clinical research trials were carried out to quantify and characterize chronic skin photodamage and longitudinal skin aging under general life style among Japanese women in Japan. First, we investigated chronic photodamage on the facial skin among totally 602 Japanese women who permanently lived in two different locations between Akita (low annual sun UV exposure) and Kagoshima (high UV exposure), and observed there were statistically significant worse in visible signs of skin aging such as skin darkness, wrinkles and hyperpigmented spots among the subjects who lived in Kagoshima than those of lived in Akita, especially age over 45. Second, we have trucked longitudinal facial skin aging over 11 years among 108 Japanese women who permanently lived in Akita. We found facial skin aging appearances and its longitudinal progression were not equally to all individuals, and variation of chronic skin aging appearances became larger by age, even over age 70. It was also demonstrated that their skin care habits and practice influenced on the variation of skin aging. For example, subjects who frequent used sun-screen and/or skin whitening formula over 11 years showed better visible appearances of facial skin such as hyperpigmentation and wrinkles.

Even though human beings and society have changed, our awareness of beautifully dressing ourselves and seeing others has not changed. Cosmetics start to encouragement with others as well as having a sense of happiness. Cosmetic can be dressed not only superficially but also my own heart. For these reasons, there is full trust in using them. On the both side of making and using, the high quality and safety of products created with advanced technology are shared and understood. We can see the advanced scientific images with guarantee safety in cosmetic fields enhancing to high applied sciences and making excellent products by utilizing of advanced information and technology obtained in basic science. When transitioning from the 20th century of micro to the new century of the 21st century, it is expected to be used industrial nanomaterials in various fields. Regarding nanomaterials, they were subjects of different categories from conventional chemical substances, such as concepts and evaluation methods. Scientific studies have begun, with understanding that it is important to evaluate safety and to take countermeasures before being used, rather than after accumulating information after use. For cosmetics, the use of nanomaterials of various basic materials and forms was being considered. Therefore, examination was advanced on safety, include a wide range of research fields and technologies such as information on physicochemical properties of materials, state of existence in products, physiology of skin, mechanisms of absorption/metabolism/excretion, influence of environmental factors, analysis techniques. Although studies supported by such various fields on nano industrial materials will continue, it is well known that enormous achievements are also accumulated and safety is ensured in cosmetics. In this way, I trust that advanced technology for productization and efforts to evaluate safety are the cornerstones that cosmetics can be used with relief.

In quitting the president of the Japanese cosmetic science society, I looked back on the ten years in office and described the results during the interim and the remaining issues. The greatest achievement is the formulation of guidelines for evaluation of cosmetic functions. In the guidelines, four committees formulated guidelines for evaluation of anti-wrinkle products, whitening products, sunscreen products, and evaluation of safety of functional cosmetics. The most memorable result is that anti-wrinkle cosmetics and quasi drugs were recognized as new efficacy for the first time in more than 30 years. On the other hand, we saw multiple occurrences of leukoderma due to side effects of a whitening product. Based on that, a new safety test was obliged. As for the sunscreen products, we are looking forward to being able to claim the efficacy that photoaging can be prevented by daily use. However, since the educational activities have not been fully developed, there are few people who understand the meaning of photoaging correctly. This indication of efficacy leads not only to prevention of photoaging but also prevention of skin cancer. Thus, it must be achieved in order to extend the healthy life expectancy of the people and to control medical expenses.

The first in man application of iPS-derived cells started in September 2014 targeted the retinal disease called age-related macular degeneration (AMD). AMD is caused by the senescence of a layer of the retina called retinal pigment epithelium (RPE). It is the major cause of visual impairment in advanced countries. We aim to develop a treatment that replace damaged RPE with normal, young RPE made from patients' own iPS cells to rescue photoreceptors in the neural retina. In the clinical study, we generated iPS cells from patient's skin fibroblast. RPE cells were differentiated from iPS cells. Picking up the brown cluster of cells, hiPS-RPE cells were purified. Cells were evaluated their purity, function, various genetic examination and tumorigenicity test using mice to check the safety. We judged the outcome 1 year after the surgery. Primary endpoint; the safety was successfully achieved in the first case as we expected. However, autologous transplantation is time consuming and the cost is high. It is necessary to prepare allogeneic transplantation to establish a standard treatment. RPE cells are suitable for allogeneic transplantation because they suppress the immunoreaction and it is possible that the rejection is considerably little if we use the HLA matched iPS cell. After we confirmed that HLA matched iPSC-derived RPE show no immune rejection in model animals, we announced the new clinical research using allogeneic transplantation of iPSC-derived RPE. In Japan pharmaceutical law has been changed and a new chapter for regenerative medicine was established. This is the first law specific for regenerative medicine in the world. It was determined in the co-operation with ministry & academia and its success will depend on the co-operation of regulatory authorities, academia and companies.