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Hemiterpene compound, 3,3-dimethylallyl alcohol promotes longevity and neuroprotection in Caenorhabditis elegans.
GeroScience ( IF 5.6 ) Pub Date : 2020-07-28 , DOI: 10.1007/s11357-020-00241-w
Suresh Chandra Phulara 1 , Swapnil Pandey 2, 3 , Anubhuti Jha 4 , Puneet Singh Chauhan 2, 3 , Pratima Gupta 4 , Virendra Shukla 5
Affiliation  

Terpenes and their derivatives have been used conventionally as potential dietary supplements to boost the nutritional value of endless food products. Several plant-based complex terpenoid and their derivatives have been reported for a wide range of medicinal and nutritional properties. However, their simple counterparts, whose production is relatively easy, sustainable, and economic from food-grade microbial sources, have not been studied yet for any such biological activities. The present study aimed to investigate the longevity-promoting property and neuromodulatory effects of 3,3-dimethylallyl alcohol (Prenol), one of the simplest forms of terpenoid and a constituent of fruit aroma, in the animal model Caenorhabditis elegans. Prenol supplementation (0.25 mM) augmented the lifespan of wild-type nematodes by 22.8% over the non-treated worms. Moreover, a suspended amyloid-β induced paralysis and reduced α-synuclein aggregation were observed in Prenol-treated worms. The lifespan extending properties of Prenol were correlated with ameliorated physiological parameters and increased stress (heat and oxidative) tolerance in C. elegans. In silico and gene-specific mutant studies showed that pro-longevity transcription factors DAF-16, HSF-1, and SKN-1 were involved in the improved lifespan and health-span of Prenol-treated worms. Transgenic green fluorescent protein-reporter gene expression analysis and relative mRNA quantification (using real-time PCR) demonstrated an increase in the expression of DAF-16, HSF-1, and SKN-1 transcription factors and their downstream target genes in Prenol-treated worms. Together, the findings suggest that small molecules, like Prenol, could be explored as a potential alternate to develop therapeutics against aging and age-related ailments.



中文翻译:

半萜化合物 3,3-二甲基烯丙醇可促进秀丽隐杆线虫的寿命和神经保护。

萜烯及其衍生物通常被用作潜在的膳食补充剂,以提高无尽食品的营养价值。据报道,几种基于植物的复合萜类化合物及其衍生物具有广泛的药用和营养特性。然而,它们的简单对应物,其生产相对容易、可持续且经济地来自食品级微生物来源,尚未研究任何此类生物活性。本研究旨在研究 3,3-二甲基烯丙醇(Prenol)(最简单形式的萜类化合物之一,也是水果香气的成分)在动物模型秀丽隐杆线虫中的长寿特性和神经调节作用。与未经处理的线虫相比,补充异戊二烯醇 (0.25 mM) 可将野生型线虫的寿命延长 22.8%。此外,在经异戊烯醇处理的蠕虫中观察到悬浮的淀粉样蛋白-β诱导的麻痹和α-突触核蛋白聚集的减少。异戊二烯醇的寿命延长特性与线虫生理参数的改善和应激(热和氧化)耐受性的增加相关。计算机模拟和基因特异性突变研究表明,延长寿命的转录因子 DAF-16、HSF-1 和 SKN-1 与经 Prenol 处理的线虫寿命和健康寿命的延长有关。转基因绿色荧光蛋白报告基因表达分析和相对 mRNA 定量(使用实时 PCR)表明,经 Prenol 处理的 DAF-16、HSF-1 和 SKN-1 转录因子及其下游靶基因的表达增加蠕虫。总之,这些发现表明,像异戊烯醇这样的小分子可以作为潜在的替代品来开发对抗衰老和与年龄相关的疾病的疗法。

更新日期:2020-07-29
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