Disparate patterns of age-related changes in lipid peroxidation in long-lived naked mole-rats and shorter-lived mice
Disparate patterns of age-related changes in lipid peroxidation in long-lived naked mole-rats and shorter-lived mice
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DOI：
10.1111/j.1474-9726.2006.00246.x
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发表时间：
2006-12-01
期刊：
影响因子：
7.8
通讯作者：
Buffenstein, Rochelle
中科院分区：
文献类型：
--
作者：
Andziak, Blazej;Buffenstein, Rochelle
衰老的氧化应激理论的一个关键原则是，累积的氧化损伤水平随着年龄的增长而增加。因此，损害产生和积累的差异可能是物种寿命自然变化的基础。我们比较了长寿裸鼹鼠[最大寿命（MLS）> 28.3岁]和寿命较短的CB6F1杂交小鼠（MLS类似于3.5岁）的全生物体脂质过氧化（尿异前列腺素）和肝脏脂质损伤（丙二醛）的年龄相关特征。此外，我们比较了肝脏非血红素铁的年龄相关变化，以评估细胞内条件，这可能会调节氧化过程，受衰老的影响。令人惊讶的是，即使在年轻的时候，裸鼹鼠的两种脂质过氧化标记物和铁的浓度至少是小鼠的两倍（P < 0.005）。这驳斥了裸鼹鼠长寿是由于对氧化应激的上级保护的假设。所有这三个参数的年龄相关的配置文件是明显的物种特异性。小鼠的脂质损伤产生率在整个成年期都保持不变，而老年动物的累积损伤是年轻小鼠的两倍。裸鼹鼠尿中异前列腺素排泄量随年龄增长而减少一半（P < 0.001），尽管组织铁增加（P < 0.05）。与氧化应激理论的预测相反，鼹鼠的脂质损伤水平并不随年龄的变化而变化。这些数据表明，氧化应激标志物水平的年龄相关变化的模式是物种特异性的，裸鼹鼠的显着寿命是独立的氧化应激参数。
A key tenet of the oxidative stress theory of aging is that levels of accrued oxidative damage increase with age. Differences in damage generation and accumulation therefore may underlie the natural variation in species longevity. We compared age-related profiles of whole-organism lipid peroxidation (urinary isoprostanes) and liver lipid damage (malondialdehyde) in long living naked mole-rats [maximum lifespan (MLS) > 28.3 years] and shorter-living CB6F1 hybrid mice (MLS similar to 3.5 years). In addition, we compared age-associated changes in liver non-heme iron to assess how intracellular conditions, which may modulate oxidative processes, are affected by aging. Surprisingly, even at a young age, concentrations of both markers of lipid peroxidation, as well as of iron, were at least twofold (P < 0.005) greater in naked mole tats than in mice. This refutes the hypothesis that prolonged naked mole-rat longevity is due to superior protection against oxidative stress. The age-related profiles of all three parameters were distinctly species specific. Rates of lipid damage generation in mice were maintained throughout adulthood, while accrued damage in old animals was twice that of young mice. In naked mole-rats, urinary isoprostane excretion declined by half with age (P < 0.001), despite increases in tissue iron (P < 0.05). Contrary to the predictions of the oxidative stress theory, lipid damage levels did not change with age in mole-rats. These data suggest that the patterns of age-related changes in levels of markers of oxidative stress are species specific, and that the pronounced longevity of naked mole-rats is independent of oxidative stress parameters.