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

Exp Dermatol. 2017 Oct;26(10):889-895. doi: 10.1111/exd.13323. Epub 2017 May 3.


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 H2AX-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.

Keywords: HGPS; ageing; metformin; progerin; senescence.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Animals
  • Cell Line
  • Cell Nucleus / metabolism
  • Cell Proliferation / drug effects*
  • Cellular Senescence / drug effects*
  • Child
  • Child, Preschool
  • Fibroblasts / metabolism
  • Gene Expression / drug effects*
  • Histones / metabolism
  • Humans
  • Hypoglycemic Agents / pharmacology*
  • Lamin Type A / metabolism
  • Metformin / pharmacology*
  • Mice
  • Nuclear Proteins / metabolism
  • Phenotype
  • Phosphorylation / drug effects
  • Progeria / pathology
  • Progeria / physiopathology*
  • RNA, Messenger / metabolism
  • Reactive Oxygen Species / metabolism
  • Skin / pathology
  • Spleen / cytology
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism


  • H2AX protein, human
  • Histones
  • Hypoglycemic Agents
  • Lamin Type A
  • Nuclear Proteins
  • RNA, Messenger
  • Reactive Oxygen Species
  • prelamin A
  • Metformin
  • Superoxide Dismutase
  • AMP-Activated Protein Kinases