CALORIC RESTRICTION ATTENUATES PROTEIN OXIDATIVE DAMAGE IN AGING MICE

氧化损伤，特别是对蛋白质的氧化损伤，已经广泛存在。 被认为是功能丧失的一个主要诱因 在衰老过程中的能力。各种机制的性质 可能对蛋白质氧化有贡献，目前还只有部分了解。在……里面 这项研究，氧化损伤的两个标记物的浓度， 用稳定同位素测定了O，O‘-二酪氨酸和O-酪氨酸 稀释气相色谱-质谱法测定银杏叶四种组织的含量 青年时期的小鼠，即心脏、骨骼肌、脑和肝脏(4 成年(14个月大)和老年(30个月大)。一个 比较了摄入无限量卡路里的小鼠 而那些被限制在卡路里摄入量的60%的人 自由发挥的养生法。体外研究表明， O，O‘-二氢酪氨酸在暴露于低密度脂蛋白中选择性地产生 酪氨酸基。氧化的蛋白质中O-酪氨酸增加 羟基自由基，这也导致了可变的公司在 O，O‘-二氨基酪氨酸。在随意喂食的小鼠中， 心肌和骨骼肌中的O，O‘-二硫酪氨酸随年龄增长而增加，但 不是在肝脏或大脑中。相比之下，o-酪氨酸水平并没有上升。 在检查的任何组织中都有年龄。这些结果表明， 酪氨酸基诱导的蛋白质氧化选择性增加 骨骼肌和心脏的年龄。卡路里限制防止了 心肌和骨骼肌中O，O‘-二硫酪氨酸水平增加，但 对上述四种组织中的邻酪氨酸水平均无影响。这 O，O‘-二氢酪氨酸水平的选择性升高及其预防 延长生命的卡路里限制方案增加了这种可能性 酪氨酸自由基氧化肌肉蛋白质有助于 心脏和骨骼肌功能的恶化 年事已高。

Oxidative damage, particularly to proteins, has been widely postulated to be a major causitive factor in the loss of functional capacity during senescence. The nature of the various mechanisms that may contribute to protein oxidation is only partially understood. In this study, concentrations of two markers for oxidative damage, o,o'-dityrosine and o-tyrosine, were determined using stable isotope dilution gas chromatography-mass spectrometry in four tissues of the mouse, namely heart, skeletal muscle, brain and liver during youth (4 month old), adulthood (14 month old) and old (30 month old) age. A comparison was made between mice that had access to unlimited calories with those that were restricted to 60 % of the caloric intake of the ad libitum regimen. In vitro studies demonstrated that o,o'-dityrosine was generated selectively in proteins exposed to tyrosyl radical. o-Tyrosine increased in proteins oxidized with hydroxyl radical, which also resulted in a va riable inc rease in o,o'-dityrosine. In the ad-libitum fed mice, levels of o,o'-dityrosine increased with age in cardiac and skeletal muscle but not in liver or brain. In contrast, o-tyrosine levels did not rise with age in any of the tissues examined. These results suggest that tyrosyl radical-induced protein oxidation increases selectively with age in skeletal muscle and heart. Caloric restriction prevented the increase in o,o'-dityrosine levels in cardiac and skeletal muscle but did not influence o-tyrosine levels in any of the four tissues. This selective increase in o,o'-dityrosine levels and its prevention by life-prolonging caloric restriction regimen raises the possibility that oxidation of muscle proteins by tyrosyl radical contributes to the deterioration of cardiac and skeletal muscle function with advancing age.