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

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

Fang J1,2, Yang J1,2, Wu X1,2, Zhang G1,2, Li T1,2, Wang X1, Zhang H1,2, Wang CC1,2, Liu GH1,2,3, Wang L1,2.

Author information

1
National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
2
College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.
3
National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital of Capital Medical University, Beijing, China.

Abstract

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

PMID:
29659168
PMCID:
PMC6052468
DOI:
10.1111/acel.12765
[Indexed for MEDLINE]
Free PMC Article

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