Metformin inhibits age-related centrosome amplification in Drosophila midgut stem cells through AKT/TOR pathway

Publication date: Available online 16 May 2015 Source:Mechanisms of Ageing and Development Author(s): Hyun-Jin Na , Joung-Sun Park , Jung-Hoon Pyo , Ho-Jun Jeon , Young-Shin Kim , Robert Arking , Mi-Ae Yoo We delineated the mechanism regulating the inhibition of centrosome amplification by metformin in Drosophila intestinal stem cells (ISCs). Age-related changes in tissue-resident stem cells may be closely associated with tissue aging and age-related diseases, such as cancer. Centrosome amplification is a hallmark of cancers. Our recent work showed that Drosophila ISCs are an excellent model for stem cell studies evaluating age-related increase in centrosome amplification. Here, we showed that metformin, a recognized anti-cancer drug, inhibits age- and oxidative stress-induced centrosome amplification in ISCs. Furthermore, we revealed that this effect is mediated via down-regulation of AKT/target of rapamycin (TOR) activity, suggesting that metformin prevents centrosome amplification by inhibiting the TOR signalling pathway. Additionally, AKT/TOR signalling hyperactivation and metformin treatment indicated a strong correlation between DNA damage accumulation and centrosome amplification in ISCs, suggesting that DNA damage might mediate centrosome amplification. Our study reveals the beneficial and protective effects of metformin on centrosome amplification via AKT/TOR signalling modulation. We identified a new target for the inhibition of age- and oxidative stress-...
Source: Mechanisms of Ageing and Development - Category: Geriatrics Source Type: research