Reynolds Oklahoma Center on Aging, Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, USA.
J Gerontol A Biol Sci Med Sci. 2011 Jul;66(7):741-50. doi: 10.1093/gerona/glr044. Epub 2011 Apr 12.
We assess whether reactive oxygen species production and resistance to oxidative stress might be causally involved in the exceptional longevity exhibited by the ocean quahog Arctica islandica. We tested this hypothesis by comparing reactive oxygen species production, resistance to oxidative stress, antioxidant defenses, and protein damage elimination processes in long-lived A islandica with the shorter-lived hard clam, Mercenaria mercenaria. We compared baseline biochemical profiles, age-related changes, and responses to exposure to the oxidative stressor tert-butyl hydroperoxide (TBHP). Our data support the premise that extreme longevity in A islandica is associated with an attenuated cellular reactive oxygen species production. The observation of reduced protein carbonyl concentration in A islandica gill tissue compared with M mercenaria suggests that reduced reactive oxygen species production in long-living bivalves is associated with lower levels of accumulated macromolecular damage, suggesting cellular redox homeostasis may determine life span. Resistance to aging at the organismal level is often reflected in resistance to oxidative stressors at the cellular level. Following TBHP exposure, we observed not only an association between longevity and resistance to oxidative stress-induced mortality but also marked resistance to oxidative stress-induced cell death in the longer-living bivalves. Contrary to some expectations from the oxidative stress hypothesis, we observed that A islandica exhibited neither greater antioxidant capacities nor specific activities than in M mercenaria nor a more pronounced homeostatic antioxidant response following TBHP exposure. The study also failed to provide support for the exceptional longevity of A islandica being associated with enhanced protein recycling. Our findings demonstrate an association between longevity and resistance to oxidative stress-induced cell death in A islandica, consistent with the oxidative stress hypothesis of aging and provide justification for detailed evaluation of pathways involving repair of free radical-mediated macromolecular damage and regulation of apoptosis in the world's longest-living non-colonial animal.
我们评估活性氧（ROS）的产生和对氧化应激的抗性是否可能是海洋圆蛤（Arctica islandica）表现出异常长寿的原因。我们通过比较长寿命的 A 岛蛤（Arctica islandica）和短寿命的硬蛤（Mercenaria mercenaria）的 ROS 产生、对氧化应激的抗性、抗氧化防御和蛋白质损伤消除过程来检验这一假设。我们比较了基线生化特征、与年龄相关的变化以及对氧化应激源叔丁基过氧化物（TBHP）暴露的反应。我们的数据支持这样一个前提，即 A 岛蛤的极端长寿与细胞内 ROS 产生的减弱有关。与 M 蛤相比，A 岛蛤鳃组织中蛋白质羰基浓度降低的观察结果表明，长寿双壳类动物中 ROS 产生减少与积累的大分子损伤水平降低有关，这表明细胞内氧化还原平衡可能决定寿命。在机体水平上对衰老的抵抗力通常反映在细胞水平上对氧化应激剂的抵抗力上。在 TBHP 暴露后，我们不仅观察到与长寿相关的与氧化应激诱导的死亡率的抵抗力之间存在关联，而且在寿命更长的双壳类动物中也观察到对氧化应激诱导的细胞死亡有明显的抵抗力。与氧化应激假说的一些预期相反，我们观察到 A 岛蛤既没有比 M 蛤更大的抗氧化能力或特定活性，也没有在 TBHP 暴露后表现出更明显的稳态抗氧化反应。该研究也未能提供支持 A 岛蛤异常长寿与增强蛋白质回收有关的证据。我们的研究结果表明，A 岛蛤的寿命与对氧化应激诱导的细胞死亡的抵抗力之间存在关联，这与衰老的氧化应激假说一致，并为详细评估涉及修复自由基介导的大分子损伤和调节凋亡的途径提供了依据，这是世界上最长寿的非殖民地动物。
