Division of Biomedical and Life Sciences, School of Health and Medicine, Lancaster University, United Kingdom.
Ageing Res Rev. 2013 Jan;12(1):404-12. doi: 10.1016/j.arr.2012.03.011. Epub 2012 Apr 5.
Drosophila and Caenorhabditis elegans have provided the largest body of evidence addressing the Free Radical Theory of ageing, however the evidence has not been unequivocally supportive. Oxidative damage to DNA is probably not a major contributor, damage to lipids is assuming greater importance and damage to proteins probably the source of pathology. On balance the evidence does not support a primary role of oxidative damage in ageing in C. elegans, perhaps because of its particular energy metabolic and stress resistance profile. Evidence is more numerous, varied and consistent and hence more compelling for Drosophila, although not conclusive. However there is good evidence for a role of oxidative damage in later life pathology. Future work should: 1/ make more use of protein oxidative damage measurements; 2/ use inducible transgenic systems or pharmacotherapy to ensure genetic equivalence of controls and avoid confounding effects during development; 3/ to try to delay ageing, target interventions which reduce and/or repair protein oxidative damage.
果蝇和秀丽隐杆线虫为衰老的自由基理论提供了最大量的证据，然而这些证据并没有明确的支持。DNA 的氧化损伤可能不是主要因素，脂质的损伤变得越来越重要，而蛋白质的损伤可能是病理学的根源。总的来说，证据并不支持氧化损伤在秀丽隐杆线虫衰老中起主要作用，这也许是因为它具有特殊的能量代谢和抗应激能力。证据在果蝇中更多、更广泛、更一致，因此更有说服力，尽管还不是结论性的。然而，有充分的证据表明氧化损伤在生命后期的病理学中起作用。未来的工作应该：1/ 更多地利用蛋白质氧化损伤的测量；2/ 使用诱导型转基因系统或药物治疗来确保对照的遗传等效性，并避免在发育过程中的混杂效应；3/ 试图延缓衰老，针对干预措施，减少和/或修复蛋白质的氧化损伤。
