4.7 Article

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

Journal

ISCIENCE
Volume 25, Issue 12, Pages -

Publisher

CELL PRESS
DOI: 10.1016/j.isci.2022.105539

Keywords

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Funding

  1. National Natural Science Foundation of China [32060033, 32160037]
  2. Innovation and Entrepreneurship Project for College Students [ZYDC2020086]

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Inhibition of mTOR has been suggested as a strategy to promote lifespan and delay age-related diseases in various organisms. Usnic Acid extended healthy lifespan by acting on mTOR and delaying neurodegenerative diseases through a mTOR-dependent manner.
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 mu M 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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