Gender differences in free radical homeostasis during aging: shorter-lived female C57BL6 mice have increased oxidative stress
Gender differences in free radical homeostasis during aging: shorter-lived female C57BL6 mice have increased oxidative stress
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DOI：
10.1111/j.1474-9726.2006.00252.x
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发表时间：
2006-12-01
期刊：
影响因子：
7.8
通讯作者：
Quick, Kevin L.
中科院分区：
文献类型：
--
作者：
Ali, Sameh S.;Xiong, Chengjie;Quick, Kevin L.
性别是衰老和寿命的深刻决定因素，但人们对自由基稳态中的性别差异知之甚少。自由基被认为是多因素衰老过程中的关键因素，据预测，长寿的性别应该有较低的氧化应激水平。虽然大多数关于衰老的研究都只包括一种性别，但最近在老鼠身上进行的研究比较了性别，发现女性寿命较长，其氧化应激和线粒体功能障碍的程度低于男性。我们在C57BL6小鼠中探索了氧化应激与性别特异性衰老的关系，其中雌性是寿命较短的性别。用脑内二氢乙锭(DHE)氧化的共聚焦成像和分离的脑线粒体的电子顺磁共振(EPR)谱测定了幼龄和老年小鼠的活性氧(ROS)。两种性别的ROS都表现出显著的年龄相关性增加。然而，随着年龄的增长，女性在DHE氧化方面比男性有更大的增加，但线粒体EPR没有增加。老年女性的超氧化物歧化酶1和谷胱甘肽过氧化物酶1的蛋白水平较低。为了确定增强抗氧化剂防御能力是否会消除寿命中的性别差异，对小鼠进行了一种超氧化物歧化酶模拟物的长期治疗。治疗阻止了ROS的年龄依赖性增加，女性对DHE氧化的影响更大，但对线粒体EPR的影响不大。治疗也在更大程度上延长了女性的寿命。我们的结果表明，ROS动态平衡的差异导致了生存的性别差异，但也表明线粒体超氧化物的产生可能不是性别寿命差异的主要原因。
Gender is a profound determinant of aging and lifespan, but little is known about gender differences in free radical homeostasis. Free radicals are proposed as key elements in the multifactorial process of aging and it is predicted that the longer-lived gender should have lower levels of oxidative stress. While the majority of studies on aging have included a single gender, recent studies in rats compared genders and found that females, the longer-lived sex, had lower oxidative stress and mitochondrial dysfunction than males. We explored the association between oxidative stress and gender-specific aging in C57BL6 mice, in which females are the shorter-lived gender. Reactive oxygen species (ROS) were measured in young and old mice by confocal imaging of dihydroethidium (DHE) oxidation in the brain, and by electron paramagnetic resonance (EPR) spectrometry of isolated brain mitochondria. Both genders exhibited significant age-dependent increases in ROS. However, females had a greater increase with age than males in DHE oxidation but not mitochondrial EPR. Superoxide dismutase 1 (Sod1) and glutathione peroxidase 1 (GPx1) protein levels were lower in old females. To determine whether enhancing antioxidant defenses would eliminate gender differences in lifespan, mice were treated chronically with a superoxide dismutase mimetic. Treatment blocked the age-dependent increase in ROS, with a greater effect in females on DHE oxidation, but not mitochondrial EPR. Treatment also increased lifespan to a greater degree in females. Our results indicate that differences in ROS homeostasis contribute to gender divergence in survival, but also suggest that mitochondrial superoxide production may not be primarily responsible for gender differences in lifespan.