Superoxide dismutase mimetics elevate superoxide dismutase activity in vivo but do not retard aging in the nematode Caenorhabditis elegans
Superoxide dismutase mimetics elevate superoxide dismutase activity in vivo but do not retard aging in the nematode Caenorhabditis elegans
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DOI：
10.1016/j.freeradbiomed.2004.04.005
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发表时间：
2004-07-15
影响因子：
7.4
通讯作者：
Gems, D
中科院分区：
文献类型：
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作者：
Keaney, M;Matthijssens, F;Gems, D
根据氧化损伤理论，衰老的主要原因是来自活性氧（ROS），特别是超氧化物及其衍生物的分子损伤的累积。这预示着降低ROS水平的治疗应该延缓衰老。使用线虫秀丽隐杆线虫，我们测试了与EUK-8和EUK-134，抗氧化酶超氧化物歧化酶（SOD），其中和超氧化物的合成模拟物处理的抗应激性和寿命的影响。用SOD模拟物处理可以提高体内SOD活性水平，特别是在线粒体中，其中SOD活性增加了5倍。外源性SOD模拟物治疗不影响内源性蛋白质SOD水平。当超氧化物发生剂百草枯和白花丹精降低寿命时，EUK-8处理以剂量依赖的方式增加寿命。然而，在没有超氧化物发生器的情况下，用EUK-8或EUK-134治疗并没有增加寿命，即使是在最佳剂量下保护免受促氧化剂的影响。因此，当超氧化物生成剂限制时，足以增加寿命的SOD活性水平的升高在没有超氧化物生成剂的情况下不会延缓衰老。这表明，线虫的寿命通常不受超氧化物及其衍生物水平的限制。(C)2004年爱思唯尔公司All rights reserved.
According to the oxidative damage theory a primary cause of aging is the accrual of molecular damage from reactive oxygen species (ROS), particularly superoxide and its derivatives. This predicts that treatments that reduce ROS levels should retard aging. Using the nematode Caenorhabditis elegans, we tested the effects on stress resistance and life span of treatment with EUK-8 and EUK-134, synthetic mimetics of the antioxidant enzyme superoxide dismutase (SOD), which neutralises superoxide. Treatment with SOD mimetics elevated in vivo SOD activity levels, particularly in mitochondria, where up to 5-fold increases in SOD activity were recorded. Treatment with exogenous SOD mimetics did not affect endogenous protein SOD levels. Where life span was reduced by the superoxide generators paraquat and plumbagin, EUK-8 treatment increased life span in a dose-dependent fashion. Yet in the absence of a superoxide generator, treatment with EUK-8 or EUK-134 did not increase life span, even at doses that were optimal for protection against pro-oxidants. Thus, an elevation of SOD activity levels sufficient to increase life span when it is limited by superoxide generators does not retard aging in the absence of superoxide generators. This suggests that C elegans life span is not normally limited by levels of superoxide and its derivatives. (C) 2004 Elsevier Inc. All rights reserved.