衰老
细胞生物学
粒体自噬
线粒体
生物
活性氧
线粒体ROS
自噬
氧化应激
细胞凋亡
遗传学
生物化学
作者
Yasunori Fujita,Masumi Iketani,Masafumi Ito,Ikuroh Ohsawa
标识
DOI:10.1016/j.exger.2022.111866
摘要
Mitochondria are dysfunctional in post-senescent cells. Therefore, age-dependent impairment of mitochondrial energy production accompanied by excessive mitochondrial reactive oxygen species (ROS) is proposed to be a key driver of cellular senescence, which is a state of irreversible cell cycle arrest. However, it remains to be clarified whether mitochondrial dysfunction initiates or accelerates replicative senescence. In this study, we observed no increase in mitochondrial ROS or decrease in mitochondrial respiratory function in human TIG-1 fibroblasts in the transition phase, during which the population doubling rate gradually decreases due to the development of replicative senescence. The integrated stress response and expression of growth differentiation factor 15, which are triggered by respiratory chain deficiency, were also not induced in the transition phase. Mitochondria were elongated without aberrant cristae structures in the transition phase. Mitophagy-related protein levels started to decrease in the transition phase, but autophagic flux slightly increased during replicative senescence. These results suggest that mitochondrial dysfunction and excessive mitochondrial ROS generation do not occur predominately in the transition phase and may not play a role in the development of replicative senescence in normal diploid TIG-1 fibroblasts.
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