Metformin alleviates ageing cellular phenotypes in Hutchinson–Gilford progeria syndrome dermal fibroblasts

Abstract Metformin is a popular antidiabetic biguanide, which has been considered as a candidate drug for cancer treatment and ageing prevention. Hutchinson–Gilford progeria syndrome ( HGPS ) is a devastating disease characterized by premature ageing and severe age‐associated complications leading to death. The effects of metformin on HGPS dermal fibroblasts remain largely undefined. In this study, we investigated whether metformin could exert a beneficial effect on nuclear abnormalities and delay senescence in fibroblasts derived from HGPS patients. Metformin treatment partially restored normal nuclear phenotypes, delayed senescence, activated the phosphorylation of AMP ‐activated protein kinase and decreased reactive oxygen species formation in HGPS dermal fibroblasts. Interestingly, metformin reduced the number of phosphorylated histone variant H2 AX ‐positive DNA damage foci and suppressed progerin protein expression, compared to the control. Furthermore, metformin‐supplemented aged mice showed higher splenocyte proliferation and mRNA expression of the antioxidant enzyme, superoxide dismutase 2 than the control mice. Collectively, our results show that metformin treatment alleviates the nuclear defects and premature ageing phenotypes in HGPS fibroblasts. Thus, metformin can be considered a promising therapeutic approach for life extension in HGPS .