Metformin alleviates ageing cellular phenotypes in Hutchinson-Gilford progeria syndrome dermal fibroblasts
- Authors
- Park, Seul-Ki; Shin, Ok Sarah
- Issue Date
- 10월-2017
- Publisher
- WILEY
- Keywords
- ageing; HGPS; metformin; progerin; senescence
- Citation
- EXPERIMENTAL DERMATOLOGY, v.26, no.10, pp.889 - 895
- Indexed
- SCIE
SCOPUS
- Journal Title
- EXPERIMENTAL DERMATOLOGY
- Volume
- 26
- Number
- 10
- Start Page
- 889
- End Page
- 895
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/81994
- DOI
- 10.1111/exd.13323
- ISSN
- 0906-6705
- 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.
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Collections - Graduate School > Department of Biomedical Sciences > 1. Journal Articles
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