Invited review article| Volume 50, ISSUE 3, P169-176, June 2008

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Photoaging and DNA repair


      The incidence of sunlight-induced skin changes (photoaged skin, skin carcinogenesis) increases with increasing age and it is thought to be associated with an accumulation of mutations in skin cells. These mutations are mainly caused by UV exposure. The reactive oxygen species produced in UV-exposed skin can cause various kinds of DNA damages e.g., 8-oxoguanine, which are primarily repaired by the base excision repair (BER) system. In addition, UV can directly cause DNA damages; cyclobutane pyrimidine dimers (CPD) and pyrimidine-pyrimidone (6-4) photoproducts (6-4PP), both of which can be repaired by the nucleotide excision repair (NER) system.
      There have been several reports showing an age-related reduction in the DNA repair capacity in the NER, BER, and other repair systems, which contributes to the phenotypes of aging. To clarify the mechanism of skin aging, we examined the NER of skin fibroblasts from healthy donors of different ages. In a host cell reactivation assay, the cells from elderly donors exhibited a significant decline in the ability to restore transfected reporter DNA damaged by UV. In contrast, the ability to remove CPD and 6-4PP declined little with age, as assessed by an enzyme-linked immunosorbent assay. The mRNA expression of DNA repair synthesis-related genes was markedly decreased in the cells from elderly subjects as compared with those from young subjects. These results imply that the age-sensitive step took place after the damage excision in the NER, and that there is an impairment of the latter step of the NER in aging. Based on our data, as well as other reports, the reduced post-UV DNA repair capacity in aging resulting in an accumulation of UV-induced DNA damage is thus considered to be associated with the phenotypes of photoaged skin.


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      Shinichi Moriwaki received his MD from Osaka Medical College in 1986. After finishing the residency in Department of Dermatology, Faculty of Medicine, Kyoto University and Kyoto National Hospital for 2 years, he studied photobiology and molecular genetics in the doctor course of Kyoto University. He completed this course in 4 years and got the degree of Medical Sciences from Kyoto University in 1992. Shortly after that he went to Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health in the U.S. to study for 2 years as a visiting fellow under Dr. Kenneth H. Kraemer. Subsequently, he began to work as a dermatologist in Hyogo Prefectural Amagasaki Hospital. In 1997, he joined Department of Dermatology, Hamamatsu University School of Medicine and in 2000 he became an associate professor in Medical Photobiology Department, Photon Medical Center, Hamamatsu University School of Medicine. In 2005, he moved to Department of Dermatology, Osaka Medical College as an associate professor. Dr. Moriwaki conducts research in photodermatology for over 15 years and especially he is much interested in molecular pathogenesis of photosensitive genodermatoses such as xeroderma pigmentosum and its related disorders for many years.