Summary
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.
Keywords
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Biography
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.
Article info
Publication history
Published online: July 12, 2010
Accepted:
August 29,
2007
Received in revised form:
August 24,
2007
Received:
July 19,
2007
Identification
Copyright
© 2007 Japanese Society for Investigative Dermatology. Published by Elsevier Inc. All rights reserved.
