Plants and fungi metabolites as novel autophagy inducers and senescence inhibitors

Rivka Ofir
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Abstract

Premature aging can be partially explained by inefficient autophagy (the process of cellular self-digestion that recycles intracellular components) and premature senescence (cease of cellular division without cell death activation). Autophagy and senescence are among the basic biochemical pathways in plants and fungi suggesting that some of their metabolites have the potential to act as autophagy inducers (AI) and senescence inhibitors (SI) and to inhibit inflammation and human aging. Several compounds have already been identified: trehalose and resveratrol are natural compounds that act as AI; flavonoids found in fruit and vegetables (curcumin, quercetin, and fisetin) are among the first SI discovered so far. New AI/SI can be identified using various approaches like hypothesis-driven approach for screening receptor agonists using an in-silico library of thousands of natural compounds; cheminformatics studies of phytochemicals using docking and molecular dynamics simulation, structure similarities/mimicry in vitro, “blind” high throughput screening (HTS) of libraries of natural metabolites against relevant models, and more. This article aims to promote the use of plant and fungi novel resources to identify bioactive molecules relevant for healthy aging based on the knowledge that plants and fungi use autophagy and senescence mechanisms for their own survival and homeostasis. As autophagy and senescence are interconnected, how drugs targeting autophagy, senescence, or both could contribute to healthy aging in humans will be speculated.
作为新型自噬诱导剂和衰老抑制剂的植物和真菌代谢物
过早衰老的部分原因可能是低效的自噬(细胞自我消化过程,回收细胞内成分)和过早衰老(细胞停止分裂而不激活细胞死亡)。自噬和衰老是植物和真菌的基本生化途径之一,这表明它们的一些代谢物有可能作为自噬诱导剂(AI)和衰老抑制剂(SI),抑制炎症和人体衰老。目前已经发现了几种化合物:曲哈糖和白藜芦醇是作为自噬诱导剂的天然化合物;水果和蔬菜中的类黄酮(姜黄素、槲皮素和鱼黄素)是迄今发现的首批自噬抑制剂。新的 AI/SI 可以通过各种方法鉴定出来,如利用由数千种天然化合物组成的室内化合物库筛选受体激动剂的假设驱动法;利用对接和分子动力学模拟对植物化学物质进行化学信息学研究;体外结构相似性/模仿;根据相关模型对天然代谢物库进行 "盲法 "高通量筛选 (HTS),等等。基于植物和真菌利用自体吞噬和衰老机制维持自身生存和平衡的知识,本文旨在促进利用植物和真菌新资源来鉴定与健康衰老相关的生物活性分子。由于自噬和衰老是相互关联的,因此将推测针对自噬、衰老或两者的药物如何促进人类的健康衰老。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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