Metformin, an FDA-approved first-line drug fortreating type 2 diabetes mellitus, has been used clinically for over 60 years for its effectiveness, safety, and low cost. Recently, its effects on elongating lifespan have been demonstrated in some animal models. However, whether metformin can suppress human cellular aging and the mechanisms underlying its probable geroprotective effects in humans remain unclear.

In a study published online in Aging Cell, Prof. WANG Chihchen’s group and Prof. LIU Guanghui’s group at the Institute of Biophysics of Chinese Academy of Sciences (CAS) reported that chronic low-dose metformin treatment upregulates the endoplasmic reticulum-localized glutathione peroxidase 7 (GPx7) and delays aging in human cells.

The researchers report that chronic low-dose metformin treatment increases the life span of human diploid fibroblasts (HDFs) and human mesenchymal stem cells (HMSCs). Metformin activates an antioxidant transcription factor Nrf2 and transcriptionally upregulates the expression of the endoplasmic reticulum (ER)-localized GPx7.

Prof. WANG’s previous study revealed that GPx7 is a key enzyme involved in regulating the oxidative protein folding and maintaining the ER redox homeostasis. In this study, they showed that the expression of GPx7 diminishes during human cellular aging and knocking down of GPx7 accelerates the aging process of human cells.

In the Nrf2-genetically enhanced stem cells generated by Prof. LIU’s group, GPx7 protein level increased. Interestingly, metformin-Nrf2-GPx7 axis also functions in organism aging using C. elegans as a model. GPX-6 (ortholog of human GPx7) is required for the positive effects of metformin on life span extension in worms.

Their study provided insights into the beneficial effects of metformin on human cellular aging and highlighted the importance of the Nrf2-GPx7 pathway in pro-longevity signaling.