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 language | English |
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Pages (from-to) | 889-895 |
Number of pages | 7 |
Journal | Experimental Dermatology |
Volume | 26 |
Issue number | 10 |
DOIs | |
Publication status | Published - 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