Overexpression of Nmnat improves the adaption of health span in aging Drosophila

Overexpression of Nmnat improves the adaption of health span in aging Drosophila
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Nmnat 的过表达提高了衰老果蝇健康寿命的适应能力

DOI:
10.1016/j.exger.2018.04.026
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发表时间:
2018-07-15
影响因子:
3.9
通讯作者:
Zheng, Lan
Zheng, Lan
中科院分区:
医学2区
文献类型:
--
作者:
Liu, Xianchu;Liu, Ming;Zheng, Lan

文献摘要

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Nmnat是一种参与多种生物过程的应激反应蛋白。然而,Nmnat对衰老的影响尚未被研究。本研究揭示了Nmnat对果蝇衰老的影响,并揭示了其潜在机制。因此,我们通过arm/Gal4系统在果蝇中建立了Nmnat的过表达,目的是确定Nmnat在衰老过程中的功能。在本研究中,我们的研究结果表明Nmnat是延长寿命和运动能力的积极因素,这与d -半乳糖诱导的衰老加速是一致的。进一步研究发现,Nmnat过表达果蝇的氧化应激生物标志物、长寿基因、线粒体相关基因和ATP水平均显著提高,提示Nmnat影响衰老过程和运动能力的潜在机制部分与其抗氧化应激和线粒体保护功能有关。此外,在H2O2刺激试验中,Nmnat过表达足以增加果蝇的存活时间和运动能力,这可能与Nmnat对氧化应激的保护作用有关。在鱼藤酮诱导的线粒体功能障碍中,Nmnat过表达也比对照组表现出更好的健康寿命和运动能力。基于这些数据,Nmnat可能是一个新的分子靶点,通过增强衰老过程中的抗逆性和运动活性来改善健康寿命。
Nmnat is a stress response protein which has been involved in a variety of biological processes. However, the effects of Nmnat on aging have not yet been investigated. The present study revealed the effects of Nmnat on aging of Drosophila and uncovered its underlying mechanism. Therefore, the overexpression of Nmnat was established by arm/Gal4 system in Drosophila with an aim to determine the functions of Nmnat during aging process. In this study, our results showed Nmnat was a positive factor on lifespan and movement capacity, which was consistent on D-galactose induced aging acceleration. Further investigation showed that oxidative stress biomarkers, longevity gene, mitochondria related genes and ATP levels were significantly improved in the Nmnat overexpression Drosophila, which suggested that the underlying mechanism of Nmnat on aging process and movement capacity was partly due to its anti-oxidative stress and mitochondrial-protection function. In addition, on H2O2 challenge tests, Nmnat overexpression was sufficient to increase the survival time and movement capacity of Drosophila, which was probably due to its protection against oxidative stress. On rotenone induced mitochondrial dysfunction, Nmnat overexpression also showed better health span and movement capacity than the control group. Based on these data, Nmnat may be a new molecular target to improve health span by enhancing stress resistance and locomotor activity in aging process.