RRC ID 51506
Author Chen J, Ou Y, Li Y, Hu S, Shao LW, Liu Y.
Title Metformin extends C. elegans lifespan through lysosomal pathway.
Journal Elife
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.
Volume 6
Published 2017-10-13
DOI 10.7554/eLife.31268
PII 31268
PMID 29027899
PMC PMC5685485
MeSH AMP-Activated Protein Kinases / metabolism Animals Caenorhabditis elegans / drug effects* Caenorhabditis elegans / physiology* Hypoglycemic Agents / metabolism* Longevity / drug effects Lysosomes / metabolism* Mechanistic Target of Rapamycin Complex 1 / metabolism Metformin / metabolism*
IF 7.551
Times Cited 17
C.elegans tm2339 tm2367