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， 被认为是功能丧失的主要致病因素， 衰老期间的能力。 各种机制的性质， 可能有助于蛋白质氧化，只是部分了解。 在 这项研究，氧化损伤的两种标记物的浓度， 用稳定同位素法测定了O，O ′-二酪氨酸和O-酪氨酸 稀释气相色谱-质谱法在四个组织的 小鼠，即心脏，骨骼肌，大脑和肝脏在青年时期（4 月龄）、成年期（14月龄）和老年期（30月龄）。 一 研究人员对那些摄入了无限卡路里的老鼠进行了比较， 与那些限制在60%的热量摄入的人相比， 自由进食方案。 体外研究表明， o，o ′-二酪氨酸选择性地在暴露于 酪氨酰自由基 蛋白质中的邻酪氨酸增加， 羟基自由基，也导致不同程度的增加， o，o ′-二酪氨酸。 在自由进食的小鼠中， 在心肌和骨骼肌中，o，o '-二酪氨酸随年龄增加而增加， 而不是肝脏或大脑。 相比之下，o-酪氨酸水平没有上升， 随着年龄的增长而变化 这些结果表明 酪氨酰自由基诱导的蛋白质氧化选择性增加， 骨骼肌和心脏的年龄。 热量限制阻止了 心肌和骨骼肌中O，O ′-二酪氨酸水平增加， 不影响四种组织中任何一种的邻酪氨酸水平。 这 O，O ′-二酪氨酸水平的选择性增加及其预防 延长寿命的热量限制方案提高了 酪氨酰自由基对肌肉蛋白的氧化作用 心脏和骨骼肌功能的恶化， 年龄增长。

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.