Research on abnormal mitochondria and its change in gene expression in cellular senescence.

Research Project

Project/Area Number	09835001
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Single-year Grants
Section	一般
Research Field	老化(加齢)
Research Institution	Akita University (1998) Chiba University (1997)
Principal Investigator	MURANO Shunichi Akita University, School of Medicine, Associate Professor., 医学部, 助教授 (50231634)
Co-Investigator(Kenkyū-buntansha)	BUJO Hideaki Chiba University, School of Medicine, Assistant Professor., 医学部, 助手 (80291300) MORISAKI Nobuhiro Chiba University, School of Medicine, Associate Professor., 医学部, 講師 (40174411)
Project Period (FY)	1997 – 1998
Project Status	Completed (Fiscal Year 1998)
Budget Amount *help	¥2,900,000 (Direct Cost: ¥2,900,000) Fiscal Year 1998: ¥700,000 (Direct Cost: ¥700,000) Fiscal Year 1997: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywords	cellular senescence / Werner syndrome / cultured skin fibroblasts / mitochondria / oxygen damage / 抗酸化剤 / 中膜平滑筋細胞 / TIG103細胞
Research Abstract	Cultured skin fibroblasts have a limited replicative potential and it decreased by serial cultivations. This potential is called as cellular life span and its process is termed as cellular(replicative) senescence. By the way, mitochondria have charge of cellular respiratory function and indispensable in cellular maintenance. Mitochondria are always functionally exposed to oxygen and are main target of cellular damages by peroxides. Mitochondria have their own circular DNA and perform their own replication and transcription. The genes are not protected by histone proteins and do not have their own DNA repair systems. So, DNA damages are easily accumulate in mitochondrial genomes than in cellular genomes, In this research, we observed expression of mitochondrial genome by Northern analysis using a fragment of human mitochondrial DNA M1 as a probe in young and senescent cultured skin fibroblasts and fibroblasts from a patient with Werner syndrome. As a result, expressions of mitochondrial genome were decreased in senescent cells and Werner's cells than in young fibroblasts. Furthermore, we found that ratio of abnormal mitochondria being characterized by thin and long configurations, lower permiability and loss of cristae is increased in senescent cells with electron microscopy. But the morphological changes were not observed in Werner's cells which lost replicative potential by a special gene defect. Finally, these morphological changes were speculated to be induced by cumulative replications but not by replicative termination.