Usnic Acid extends healthspan and improves the neurodegeneration diseases via mTOR/PHA-4 signaling pathway in Caenorhabditis elegans
Yi Xiao,
Huiling Zhang,
Yi Sheng,
Fang Liu,
Jiajun Gao,
Guosheng Liu,
Sanhua Li,
Nian Jiang,
Changyan Yu,
Yun Liu
Affiliations
Yi Xiao
Guizhou Provincial College-based Key Lab for Tumor Prevention and Treatment with Distinctive Medicines, Zunyi Medical University, Zunyi, Guizhou 563000, China; Institute of Life Sciences, Zunyi Medical University, Zunyi, Guizhou 563000, China
Huiling Zhang
Guizhou Provincial College-based Key Lab for Tumor Prevention and Treatment with Distinctive Medicines, Zunyi Medical University, Zunyi, Guizhou 563000, China; Institute of Life Sciences, Zunyi Medical University, Zunyi, Guizhou 563000, China
Yi Sheng
Guizhou Provincial College-based Key Lab for Tumor Prevention and Treatment with Distinctive Medicines, Zunyi Medical University, Zunyi, Guizhou 563000, China; Institute of Life Sciences, Zunyi Medical University, Zunyi, Guizhou 563000, China
Fang Liu
Guizhou Provincial College-based Key Lab for Tumor Prevention and Treatment with Distinctive Medicines, Zunyi Medical University, Zunyi, Guizhou 563000, China; College of Basic Medicine, Zunyi Medical University, Zunyi, Guizhou 563000, China
Jiajun Gao
Guizhou Provincial College-based Key Lab for Tumor Prevention and Treatment with Distinctive Medicines, Zunyi Medical University, Zunyi, Guizhou 563000, China
Guosheng Liu
Guizhou Provincial College-based Key Lab for Tumor Prevention and Treatment with Distinctive Medicines, Zunyi Medical University, Zunyi, Guizhou 563000, China; College of Basic Medicine, Zunyi Medical University, Zunyi, Guizhou 563000, China
Sanhua Li
Guizhou Provincial College-based Key Lab for Tumor Prevention and Treatment with Distinctive Medicines, Zunyi Medical University, Zunyi, Guizhou 563000, China; Institute of Life Sciences, Zunyi Medical University, Zunyi, Guizhou 563000, China
Nian Jiang
Guizhou Provincial College-based Key Lab for Tumor Prevention and Treatment with Distinctive Medicines, Zunyi Medical University, Zunyi, Guizhou 563000, China; Institute of Life Sciences, Zunyi Medical University, Zunyi, Guizhou 563000, China
Changyan Yu
Guizhou Provincial College-based Key Lab for Tumor Prevention and Treatment with Distinctive Medicines, Zunyi Medical University, Zunyi, Guizhou 563000, China; Institute of Life Sciences, Zunyi Medical University, Zunyi, Guizhou 563000, China
Yun Liu
Guizhou Provincial College-based Key Lab for Tumor Prevention and Treatment with Distinctive Medicines, Zunyi Medical University, Zunyi, Guizhou 563000, China; Institute of Life Sciences, Zunyi Medical University, Zunyi, Guizhou 563000, China; College of Basic Medicine, Zunyi Medical University, Zunyi, Guizhou 563000, China; Corresponding author
Summary: 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.
