Metformin extends C. elegans lifespan through lysosomal pathway
- Peking University, China
Abstract
Metformin, a widely used first-line drug for treatment of type 2 diabetes (T2D), has been shown to extend lifespan and delay the onset of age-related diseases. However, its primary locus of action remains unclear. Using a pure in vitro reconstitution system, we demonstrate that metformin acts through the v-ATPase-Ragulator lysosomal pathway to coordinate mTORC1 and AMPK, two hubs governing metabolic programs. We further show in Caenorhabditis elegans that both v-ATPase-mediated TORC1 inhibition and v-ATPase-AXIN/LKB1-mediated AMPK activation contribute to the lifespan extension effect of metformin. Elucidating the molecular mechanism of metformin regulated healthspan extension will boost its therapeutic application in the treatment of human aging and age-related diseases.
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Funding
National Natural Science Foundation of China (31422033)
- Ying Liu
Ministry of Science and Technology of the People's Republic of China (2013CB910104)
- Ying Liu
National Natural Science Foundation of China (31471381)
- Ying Liu
Young thousand Talents Program of China
- Ying Liu
Peking-Tsinghua Center for Life Sciences
- Ying Liu
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2017, Chen et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Metformin extends C. elegans lifespan through lysosomal pathway
eLife 6:e31268.
https://doi.org/10.7554/eLife.31268
