Metformin extends C. elegans lifespan through lysosomal pathway

Metformin extends C. elegans lifespan through lysosomal pathway

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 throug...

Full description

Bibliographic Details
Main Authors: Jie Chen, Yuhui Ou, Yi Li, Shumei Hu, Li-Wa Shao, Ying Liu
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2017-10-01
Series:eLife
Subjects:
metformin
AMPK
mTOR
Online Access:https://elifesciences.org/articles/31268
Description
Summary: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.
ISSN:2050-084X

Similar Items