CALORIC RESTRICTION ATTENUATES PROTEIN OXIDATIVE DAMAGE IN AGING MICE

热量限制可减轻衰老小鼠的蛋白质氧化损伤

• 批准号: 6665857
• 负责人: CHRISTIAAN LEEUWENBURGH
• 金额: $ 15.75万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-01 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6665857
• 关键词: animal tissue; biological products; biomedical resource; drug adverse effect; environmental toxicology; liver; neoplasm /cancer; spectrometry; urinary tract

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.

氧化损伤，特别是对蛋白质的氧化损伤，已广泛 假设是功能丧失的主要因果因素 衰老期间的能力。 各种机制的性质 可能仅部分理解有助于蛋白质氧化。 在 这项研究，氧化损伤的两个标记的浓度， O，O'dityrosine和O-酪氨酸，使用稳定同位素确定 稀释气相色谱 - 质量光谱法中的四个组织 老鼠，即心脏，骨骼肌，大脑和肝脏，年轻人（4个 一个月大），成年（14个月大）和年龄（30个月大）。 一个 进行了比较，可以使用无限卡路里的小鼠 与那些仅限于60％的热量摄入量 自发方案。 体外研究表明 o，在暴露于 酪酶自由基。 氧化蛋白的O-酪氨酸增加了 羟基自由基，这也导致了VA易于放映 O，O'dityrosine。 在Ad-libitum喂养的小鼠中 o，o'dityrosine随着心脏和骨骼肌的年龄而增加，但 不在肝脏或大脑中。 相反，O-酪氨酸水平没有上升 随着任何组织的年龄。 这些结果表明 酪酶自由基诱导的蛋白氧化有选择地增加 骨骼肌肉和心脏的年龄。 热量限制阻止了 在心脏和骨骼肌肉中增加O，O'Dityrosine水平，但 在这四个组织中的任何一个中都不影响O-酪氨酸水平。 这 O，O'dityrosine水平的选择性增加及其预防 生命繁殖的热量限制方案提高了可能性 酪酶自由基对肌肉蛋白的氧化有助于 心脏和骨骼肌功能的恶化 促进年龄。