Ken-ichi Isobe Pages 1 - 10 ( 10 )
This review focuses on the stress responses and host defense systems, which affect the aging process. Various kinds of external stresses such as heat shock, UV, X-ray, drugs, infection or internal stresses such as reactive oxygen species (ROS) generated by metabolism induce damages to nucleic acids and proteins. Several long-lived mutants have been established in C. elegans, all of which are resistant to environmental stresses. In humans, individuals with Werners syndrome show early senescence. The affected gene was cloned and found to be one of DNA helicase, which may work as a repair enzyme following DNA injurious stress. DNA-damaging stresses such as alkylating agents, UV or radiation induce p53 protein expression. Enhanced expression of the p53 protein promotes DNA repair, cell-cycle arrest or apoptosis. The development and aging of the immune system were accelerated in p53-deficient mice. The defects of the repair system induce premature aging, and longevity may depend on the strength of the def ense system. Senescent human diploid fibroblasts (HDL) contain elevated amounts of the cyclin-dependent kinase inhibitor p21WAF1 (p21), which has been shown to induce cell-cycle arrest. It has been shown recently that the histone deacetylase inhibitors, sodium butyrate and trichostatin A, induce a cellular senescence-like phenotype in NIH3T3 cells or HDL and enhance p21 promoter activity. We suffer from oxidative stress under normal physiological conditions. It was to counteract such oxidative stresses that mammals developed a defense system. The major enzymes to catalyze oxygen radicals are SOD, catalase and glutathion peroxidase. The expression of Mn-SOD was shown to be induced by infectious stress. We favor the hypothesis that longevity may depend on the strength of these defense systems.
Stress, Aging, Reactive oxygen species ROS, Werner s syndrome, DNA repair, P53 protein promotes, Human diploid firbolasts HDL, Mn SOD, CS patients, Cockayne Syndrome CS
Dept. of Basic Gerontology National Institute for Longevity Sciences Aichi 474 8522 Japan