Recent progresses on anti-aging compounds and their targets in Caenorhabditis elegans

Q2 Medicine

Translational Medicine of Aging Pub Date : 2019-01-01 DOI:10.1016/j.tma.2019.11.003

Eun Ji E. Kim, Seung-Jae V. Lee

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引用次数: 11

Abstract

Searching for drugs that extend healthy lifespan and the subsequent analysis of their mechanisms of action is a crucial aspect for aging research. However, identifying both longevity-enhancing drugs and their corresponding targets is challenging. The roundworm Caenorhabditis elegans is a suitable model for such research because of its short lifespan and genetic tractability. In this perspective, we discuss recent progresses on the identification of anti-aging drugs and characterization of their targets using C. elegans as a model organism. In particular, minocycline, JZL184, monorden, and paxilline increase C. elegans lifespan by inhibiting 18S rRNA/ribosome, fatty acid amide hydrolase-4, Hsp90, and the Ca²⁺-activated K⁺ (BK) channel SLO-1, respectively. Because many factors that regulate aging and lifespan in C. elegans are evolutionarily conserved, these newly identified lifespan-extending compounds may guide the development of anti-aging medicines for humans.

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秀丽隐杆线虫抗衰老化合物及其靶点研究进展

寻找延长健康寿命的药物并对其作用机制进行后续分析是衰老研究的一个重要方面。然而，确定延长寿命的药物及其相应的目标是具有挑战性的。秀丽隐杆线虫由于其寿命短和遗传易变性，是进行此类研究的合适模型。从这个角度来看，我们讨论了以秀丽隐杆线虫为模式生物的抗衰老药物的鉴定及其靶点的表征的最新进展。特别是，米诺环素、JZL184、monorden和paxilline分别通过抑制18S rRNA/核糖体、脂肪酸酰胺水解酶-4、Hsp90和Ca2+激活的K+ (BK)通道sl1来延长秀丽隐杆线虫的寿命。由于秀丽隐杆线虫中许多调节衰老和寿命的因素在进化上是保守的，这些新发现的延长寿命的化合物可能指导人类抗衰老药物的开发。

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