Metformin extends <i>C. elegans</i> lifespan through lysosomal pathway.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 29027899.
- Also identified by DOI 10.7554/eLife.31268 and PMC identifier 5685485.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 <i>Caenorhabditis elegans</i> 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.
Medical subject headings
- Caenorhabditis elegans
- Hypoglycemic Agents
- Lysosomes
- Metformin