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Mechanism of metformin: inhibition of DNA damage and proliferative activity in Drosophila midgut stem cell.
- Source :
-
Mechanisms of ageing and development [Mech Ageing Dev] 2013 Sep; Vol. 134 (9), pp. 381-90. Date of Electronic Publication: 2013 Jul 24. - Publication Year :
- 2013
-
Abstract
- Age-related changes in stem cells could have a profound impact on tissue aging and the development of age-related diseases such as cancer. However, the effects of metformin, a recently recognized anti-cancer drug, on stem cell aging remain largely unknown. In the present study, an experiment was set up to investigate the underlying mechanism of metformin's beneficial effects on age-related changes in intestinal stem cells (ISCs) derived from Drosophila midgut. Results showed that metformin reduced age- and oxidative stress-related accumulation of DNA damage marked by Drosophila γH2AX foci and 8-oxo-dG in ISCs and progenitor cells. Metformin also inhibited age and- oxidative stress-related ISC hyperproliferation as well as intestinal hyperplasia. Our study further revealed that the inhibitory effects of metformin on DNA damage accumulation may be due to the down-regulation of age-related and oxidative stress-induced AKT activity. These data indicate that metformin has beneficial effects on age-related changes in ISCs derived from Drosophila midgut. Further, our results suggest a possible impact of DNA damage on stem cell genomic instability, which leads to the development of age-related diseases. Additionally, our study suggests that Drosophila midgut stem cells can be a suitable model system for studying stem cell biology and stem cell aging.<br /> (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)
- Subjects :
- Animals
Animals, Genetically Modified
Bromodeoxyuridine chemistry
Cell Proliferation
Cellular Senescence
DNA Damage drug effects
Drosophila metabolism
Female
Green Fluorescent Proteins metabolism
Hypoglycemic Agents chemistry
Male
Oxidative Stress
Proto-Oncogene Proteins c-akt antagonists & inhibitors
Proto-Oncogene Proteins c-akt metabolism
Signal Transduction
Temperature
Aging
Drosophila physiology
Intestines cytology
Metformin chemistry
Stem Cells cytology
Stem Cells drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1872-6216
- Volume :
- 134
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Mechanisms of ageing and development
- Publication Type :
- Academic Journal
- Accession number :
- 23891756
- Full Text :
- https://doi.org/10.1016/j.mad.2013.07.003