Usnic Acid extends healthspan and improves the neurodegeneration diseases via mTOR/PHA-4 signaling pathway in Caenorhabditis elegans

松萝酸通过mTOR/PHA-4信号通路延长秀丽隐杆线虫健康寿命并改善神经退行性疾病

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作者:Yi Xiao, Huiling Zhang, Yi Sheng, Fang Liu, Jiajun Gao, Guosheng Liu, Sanhua Li, Nian Jiang, Changyan Yu, Yun Liu

Abstract

The Mammalian/mechanistic target of rapamycin (mTOR) played a central role in cellular survival and aging. Inhibition of mTOR had been proposed as a reasonable strategy to promote lifespan and delay age-related diseases in evolutionarily diverse organisms. The study showed that lifespan extension and age-related diseases improvement could be achieved by targeting evolutionarily conserved mTOR pathways and mechanisms using pharmacological interventions. Using this approach in Caenorhabditis elegans, We found that 2 μM Usnic Acid significantly extended the healthy lifespan in wild-type animals. Furthermore, via genetic screen, we showed that Usnic Acid acted on mTOR, which was followed by the activation of PHA-4/Foxa to extend the healthy lifespan. Intriguingly, Usnic Acid also delayed neurodegeneration diseases such as Alzheimer's and polyglutamine disease through mTOR-dependent manner. Our work suggested that Usnic Acid might be a viable candidate for the prevention and treatment of aging and age-related diseases.

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