Exercise-induced Nrf2-signaling is impaired in aging
Exercise-induced Nrf2-signaling is impaired in aging
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DOI：
10.1016/j.freeradbiomed.2016.04.024
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发表时间：
2016-07-01
影响因子：
7.4
通讯作者：
Traustadottir, Tinna
中科院分区：
文献类型：
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作者：
Done, Aaron J.;Gage, Matthew J.;Traustadottir, Tinna
目的：转录因子核红细胞 2 样因子 2 (Nrf2) 是抗氧化防御的主要调节因子。动物研究数据表明，运动会显着增加 Nrf2 信号传导，并且该信号传导会随着衰老而受损，导致 II 相解毒酶的诱导减少，并且更容易受到氧化损伤。我们之前已经表明，与年轻人相比，老年人对氧化挑战的抵抗力较低，并且这种反应可以通过身体健康和植物营养素干预来改变。我们假设单次次最大运动会引起 Nrf2 核积累增加，并且这种对运动的反应会随着年龄的增长而减弱。 方法：在年轻男性 (23 +/- 1 岁，n=10) 和老年男性 (63 +/- 1，n=10) 中比较对 70% VO(2)max 30 分钟循环的 Nrf2 信号传导。在六个时间点采集血液；运动前、运动后 10 分钟、30 分钟、1 小时、4 小时和 24 小时。通过蛋白质印迹法测量全细胞和核部分、全细胞 SOD1 和 HMOX 中 Nrf2 的蛋白表达，以及下游 Nrf2-ARE 抗氧化剂 SOD1、HMOX 和 NQO1 的基因表达 (RT-PCR)，确定外周血单核细胞中的 Nrf2 信号传导。结果：各组之间蛋白表达的基线差异没有差异。运动试验使年轻组和老年组的全细胞 Nrf2 显着增加（P=0.003）。核Nrf2水平在年轻组中显着升高，但在老年组中没有显着升高（P=0.031）。运动引起年轻人中 HMOX] 和 NQ01 基因表达显着增加（分别为 P=0.006 和 P=0.055），而老年人中的基因表达则受到抑制。 SOD1 或 HMOX1 蛋白表达没有显着差异。 结论：这些发现表明，单次次最大有氧运动足以在年轻人和老年人中激活全细胞水平的 Nrf2，但核输入会随着年龄的增长而受损。此外，我们还发现老年人中 Nrf2 下游抗氧化靶点的基因表达受到抑制。这些转化数据首次证明了老年人运动后 Nrf2 活性的减弱。 (C) 2016 Elsevier Inc. 保留所有权利。
Purpose: The transcription factor nuclear erythroid-2 like factor-2 (Nrf2) is the master regulator of antioxidant defense. Data from animal studies suggest exercise elicits significant increases in Nrf2 signaling, and that signaling is impaired with aging resulting in decreased induction of phase II detoxifying enzymes and greater susceptibility to oxidative damage. We have previously shown that older adults have lower resistance to an oxidative challenge as compared to young, and that this response is modified with physical fitness and phytonutrient intervention. We hypothesized that a single bout of submaximal exercise would elicit increased nuclear accumulation of Nrf2, and that this response to exercise would be attenuated with aging.Methods: Nrf2 signaling in response to 30-min cycling at 70% VO(2)max was compared in young (23 +/- 1y, n=10) and older (63 +/- 1, n=10) men. Blood was collected at six time points; pre-exercise, and 10 min, 30 min, 1 h, 4 h, and 24 h post-exercise. Nrf2 signaling was determined in peripheral blood mononuclear cells by measuring protein expression by western blot of Nrf2 in whole cell and nuclear fractions, and whole cell SOD1, and HMOX, as well as gene expression (RT-PCR) of downstream Nrf2-ARE antioxidants SOD1, HMOX, and NQO1.Results: Baseline differences in protein expression did not differ between groups. The exercise trial elicited significant increase in whole cell Nrf2 (P=0.003) for both young and older groups. Nuclear Nrf2 levels were increased significantly in the young but not older group (P=0.031). Exercise elicited significant increases in gene expression of HMOX] and NQ01 in the young (P=0.006, and P=0.055, respectively) whereas gene expression in the older adults was repressed. There were no significant differences in SOD1 or HMOX1 protein expression.Conclusion: These findings indicate a single session of submaximal aerobic exercise is sufficient to activate Nrf2 at the whole cell level in both young and older adults, but that nuclear import is impaired with aging. Additionally we have shown repressed gene expression of downstream antioxidant targets of Nrf2 in older adults. Together these translational data demonstrate for the first time the attenuation of Nrf2 activity in response to exercise in older adults. (C) 2016 Elsevier Inc. All rights reserved.