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

Seul Ki Park, Ok Sarah Shin

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)889-895
Number of pages7
JournalExperimental Dermatology
Volume26
Issue number10
DOIs
Publication statusPublished - 2017 Oct

Bibliographical note

Funding Information:
Basic Science Research Program through the National Research Foundation of Korea (NRF), Grant/Award Number: NRF- 2016R1C1B2006493; Ministry of Science, ICT & Future Planning, Grant/Award Number: NRF-2016R1C1B2006493

Funding Information:
This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (NRF-2016R1C1B2006493). We thank Progeria Research Foundation for providing valuable reagents.

Publisher Copyright:
© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Keywords

  • HGPS
  • ageing
  • metformin
  • progerin
  • senescence

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology

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