TOP > Report & Column > The Forefront of Space Science > 2013 > Space and Aging
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Space environment increases and accumulates oxidative stress species (ROS) such as hydroxyl radicals in vivo and activate chain reactions causing excessive oxidation of lipid. ROS is a leading cause of oxidative stress and induces cellular aging. The analysis results with the DNA microarray and qRT-PCR using the spaceflight mouse skins showed a significant increase in gene expression of enzymes involved in antioxidation, as shown in Fig. 1C, especially, superoxide dismutase (SOD3) to transform superoxide anion to hydrogen peroxide, and catalase and glutathione peroxidase (GPx) to remove hydrogen peroxide. This is thought to be the result of increased ROS in the mitochondria caused by space-environment stress. However, although a significant difference was not observed in mice undergoing the short 13-day flight, the expression increased considerably in the mice on the long 13-week flight. We also confirmed an increase in gene expression of antioxidative enzymes such as glutathione transferase (GST), NAD(P)H:quinone oxidoreductase (NQO1), and heme oxygenase 1 (HO1). These results imply the increase and accumulation of oxidative stress during a long stay in space, suggesting the high possibility that it is a cause of cellular senescence. Space environment affects cell cycle Cells divide and grow in a certain cycle called the cell cycle.EThe cycle comprises the S phase where DNA is replicated, G2 phase where cell division is prepared, M phase where cell division takes place, and G1 phase where cell division completes and goes to the next DNA synthesis. In addition to the above, the stationary phase (G0 phase) includes cells fully completing cell differentiation or ones temporarily suspending cell division. A check-point mechanism is provided to monitor whether the cell cycle is progressing normally. As shown in Fig. 1C, gene expression of p21 and p16 increased during the long-period flight. p21 inhibits the phosphorylation of retinoblastoma protein (Rb) which is a cancer-suppression protein related to one of the check points, and suppresses the transition from G1 phase to S phase in the cell cycle. The expression of Gadd45g increased considerably on both short- and long-duration flights. This protein inactivates CDK1 which is an enzyme that plays a major role in the check point mechanism, and suppresses the progress of the G2 phase and the start of the M phase. It also activates p21. Thus, the inhibition and arrest of the cell cycle via Rb and/or Gadd45g are induced. These results strongly suggest that the space environment accelerates cellular senescence (Fig. 2). 
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