Sesamin suppresses aging phenotypes in adult muscular and nervous systems and intestines in a Drosophila senescence-accelerated model
Sesamin suppresses aging phenotypes in adult muscular and nervous systems and intestines in a Drosophila senescence-accelerated model
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DOI：
10.26355/eurrev_201902_17146
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发表时间：
2019-02-01
影响因子：
3.3
通讯作者：
Inoue, Y. H.
中科院分区：
文献类型：
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作者：
Le, T. D.;Nakahara, Y.;Inoue, Y. H.
目的：芝麻素是芝麻的主要木脂素成分，具有多种保健作用。先前的研究表明，芝麻素可以延长果蝇和秀丽隐杆线虫的寿命，并纠正哺乳动物中与氧化损伤相关的组织功能障碍。为了了解芝麻素的抗衰老作用，我们旨在利用果蝇衰老加速模型确定芝麻素是否可以恢复受氧化损伤阻碍的组织功能并抑制几种与衰老相关的表型。材料和方法：我们利用衰老加速模型（Sod（n1）突变体和Sod1 耗尽的果蝇）通过免疫染色实验。我们使用定量实时聚合酶链式反应 (qRT-PCR) 测定了几种抗氧化和 DNA 修复基因的表达水平。我们还通过 LC-MS/MS 鉴定了果蝇中芝麻素的代谢物。结果：我们证实芝麻素（0.35 和 2 mg/ml）可延长果蝇模型的寿命。正如在哺乳动物中观察到的，它可以被果蝇成虫吸收和代谢。喂食芝麻素可抑制年龄依赖性的运动活动损伤，并抑制体内活性氧（ROS）的积累。芝麻素延迟了肌肉中受损蛋白质的年龄依赖性积累，部分抑制了成人大脑中表现出ROS积累的多巴胺能神经元的损失，并抑制了DNA损伤的积累和肠道干细胞的过度增殖。在喂食芝麻素的成年人中，四种抗氧化基因和两种 DNA 修复基因同时上调。结论：这些观察结果代表了芝麻素在个体水平上的抗衰老作用的第一个直接证据。我们认为芝麻素通过诱导抗氧化和 DNA 修复基因在肌肉、大脑和中肠中发挥抗衰老作用，从而延长果蝇的寿命。
OBJECTIVE: Sesamin is a major lignan constituent of sesame and possesses various health-promoting effects. Previous studies have demonstrated that sesamin extends the lifespan of Drosophila and Caenorhabditis elegans and corrects oxidative damage-related tissue dysfunction in mammals. To understand its anti-aging effects, we aimed to determine whether sesamin restores tissue function hampered by oxidative damage and suppresses several aging-related phenotypes using Drosophila senescence-accelerated models.MATERIALS AND METHODS: We elucidated the anti-aging effects of sesamin on several aging-related phenotypes in the muscle, brain and midgut using the senescence-accelerated models (Sod(n1) mutant and Sod1-depleted flies) by immunostaining experiments. We determined the expression levels of several anti-oxidative and DNA repair genes using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). We also identified the metabolite of sesamin in Drosophila by LC-MS/MS.RESULTS: We confirmed that sesamin (0.35 and 2 mg/ml) extended the lifespan of the fly models. As observed in mammals, it can be absorbed and metabolized by Drosophila adults. The sesamin feeding suppressed the age-dependent impairment of locomotor activity and inhibited the accumulation of reactive oxygen species (ROS) in their bodies. Sesamin delayed the age-dependent accumulation of damaged proteins in the muscle, partially suppressed the loss of dopaminergic neurons in adult brains displaying ROS accumulation, and suppressed the accumulation of DNA damage and hyperproliferation of intestinal stem cells. Four antioxidative genes and two DNA repair genes were simultaneously upregulated in sesamin-fed adults.CONCLUSIONS: These observations represent the first direct evidence of the anti-aging effects of sesamin at the individual level. We propose that sesamin exerts anti-aging effects in the muscles, brain and midgut by inducing antioxidative and DNA repair genes, resulting in extended lifespan in flies.