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核糖诱导的晚期糖基化终产物通过改变氧化还原状态和下调沉默调节蛋白基因来缩短黑腹果蝇的寿命。

Ribose-induced advanced glycation end products reduce the lifespan in Drosophila melanogaster by changing the redox state and down-regulating the Sirtuin genes.

作者信息

Mishra Lokanath, Mishra Monalisa

机构信息

Neural Developmental Biology Lab, Department of Life Science, NIT Rourkela, Rourkela, 769008, India.

出版信息

Biogerontology. 2024 Dec 19;26(1):28. doi: 10.1007/s10522-024-10172-0.

Abstract

Advanced Glycation End (AGE) products are one such factor that accumulates during aging and age-related diseases. However, how exogenous AGE compounds cause aging is an area that needs to be explored. Specifically, how an organ undergoes aging and aging-related phenomena that need further investigation. The intestine is the most exposed area to food substances. How AGEs affect the intestine in terms of aging need to be explored. Drosophila melanogaster, a well-known model organism, is used to decode aging and age-associated phenomena. In this study, we fed Ribose induced Advanced Glycation End products (Rib-AGE) to D. melanogaster to study the aging mechanism. The Rib-AGE-induced aging was checked in Drosophila. We found a series of changes in Rib-AGE-fed flies. Reactive oxygen species (ROS) and nitric oxide species (NOs) were higher in the Rib-AGE-fed flies, and the antioxidant level was lower. The intestinal permeability was altered. The microorganism load was higher inside the gut. The structural arrangement of the gut's microfilament was found to be damaged, and the nuclear shape was found to be irregular. Cell death within the gut was elevated in comparison to control. The food intake was found to be reduced. The relative mRNA expression of the Sirtuin 2 and Sirtuin 6 gene of D. melanogaster was downregulated in Rib-AGE-fed flies compared to the control. All these findings strongly suggest that Rib-AGE accelerates aging and age-related disorders in D. melanogaster.

摘要

晚期糖基化终末产物(AGE)是衰老及与年龄相关疾病过程中积累的一个因素。然而,外源性AGE化合物如何导致衰老仍是一个有待探索的领域。具体而言,器官如何经历衰老以及与衰老相关的现象需要进一步研究。肠道是与食物物质接触最频繁的部位。AGE如何在衰老方面影响肠道有待探索。黑腹果蝇是一种著名的模式生物,被用于解读衰老及与衰老相关的现象。在本研究中,我们给黑腹果蝇喂食核糖诱导的晚期糖基化终末产物(Rib-AGE)以研究衰老机制。我们检测了Rib-AGE诱导的黑腹果蝇衰老情况。我们发现喂食Rib-AGE的果蝇出现了一系列变化。喂食Rib-AGE的果蝇体内活性氧(ROS)和一氧化氮(NO)水平较高,而抗氧化水平较低。肠道通透性发生改变。肠道内微生物负荷较高。发现肠道微丝的结构排列受损,细胞核形状不规则。与对照组相比,肠道内细胞死亡增加。食物摄入量减少。与对照组相比,喂食Rib-AGE的黑腹果蝇中沉默调节蛋白2和沉默调节蛋白6基因的相对mRNA表达下调。所有这些发现都有力地表明,Rib-AGE加速了黑腹果蝇的衰老及与衰老相关的紊乱。

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