Journal
AGING CELL
Volume 17, Issue 4, Pages -Publisher
WILEY
DOI: 10.1111/acel.12765
Keywords
aging; glutathione peroxidase 7; metformin; nuclear factor erythroid 2-related factor 2; oxidative stress; senescence
Categories
Funding
- Ministry of Science and Technology of the People's Republic of China [2016YFA0500200, 2017YFA0504000, 2015CB964800]
- National Natural Science Foundation of China [31771261, 31571163, 81625009, 81330008, 91749202]
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDA16010100]
- Youth Innovation Promotion Association of the Chinese Academy of Sciences
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Metformin, an FDA-approved antidiabetic drug, has been shown to elongate life-span in animal models. Nevertheless, the effects of metformin on human cells remain unclear. Here, we show that low-dose metformin treatment extends the life-span 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). GPx7 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.
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