Abstract
It is widely known that the aging is processed by complex mechanisms. These mechanisms include two main theories, program theory and error catastrophy theory. Other theories are mutation theory, free radical theory, cross-linkage theory, autoimmune theory and so on. However, at present, there is no established theory to account for the all phenomenon accompanying in aging. In this paper, the complex mechanism in aging is outlined, and some progeroid syndromes as a model of normal aging are also introduced including the results of our recent studies. In normal aging, the life span of fibroblast reduces and the incidence of spontaneous mutation rate increases in in vitro study. In Werner syndrome, the incidence of spontaneous mutation rate of lymphocyte or fibroblast was about ten times higher than that in normal elderly. This was mainly caused by the large deletion of gene which was studied using Southern blot analysis. This may be associated with the mechanism of aging in Werner syndrome. SV-40 transformed fibroblasts from Cockayne syndrome was highly sensitive to UV irradiation. This high sensitivity was partially recovered by the introduction of cDNA of ribonucleotide reductase which is a rate limiting enzyme of deoxyribonucleotide synthesis. This may suggest that the regulatory deficit of the initiation of DNA replication may be related to the aging in Cockayne synerome. The mechanism of aging in progeria was more complex than that in Werner syndrome or Cockayne syndrome. We have a case of aged progeria of 45 years old who had a severe systemic arteriosclerosis with calcification and cardiovascular diseases. It is suggested that aging is caused by the multi-mechanisms including the abnormalities in the DNA replication.
