Metformin alleviates human cellular aging by upregulating the endoplasmic reticulum glutathione peroxidase 7

Aging Cell. 2018 Aug;17(4):e12765. doi: 10.1111/acel.12765. Epub 2018 Apr 16.


Metformin, an FDA-approved antidiabetic drug, has been shown to elongate lifespan in animal models. Nevertheless, the effects of metformin on human cells remain unclear. Here, we show that low-dose metformin treatment extends the lifespan of human diploid fibroblasts and mesenchymal stem cells. We report that a low dose of metformin upregulates the endoplasmic reticulum-localized glutathione peroxidase 7 (GPx7). GP×7 expression levels are decreased in senescent human cells, and GPx7 depletion results in premature cellular senescence. We also indicate that metformin increases the nuclear accumulation of nuclear factor erythroid 2-related factor 2 (Nrf2), which binds to the antioxidant response elements in the GPX7 gene promoter to induce its expression. Moreover, the metformin-Nrf2-GPx7 pathway delays aging in worms. Our study provides mechanistic insights into the beneficial effects of metformin on human cellular aging and highlights the importance of the Nrf2-GPx7 pathway in pro-longevity signaling.

Keywords: aging; glutathione peroxidase 7; metformin; nuclear factor erythroid 2-related factor 2; oxidative stress; senescence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Cellular Senescence / drug effects*
  • Dose-Response Relationship, Drug
  • Endoplasmic Reticulum / drug effects*
  • Endoplasmic Reticulum / enzymology*
  • Glutathione Peroxidase / metabolism*
  • Humans
  • Longevity / drug effects
  • Metformin / pharmacology*
  • Up-Regulation / drug effects*


  • Metformin
  • Glutathione Peroxidase