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

Hyun-Jin Na1, Joung-Sun Park1, Jung-Hoon Pyo1

  • 1Department of Molecular Biology, Pusan National University, Busan 609-735, South Korea.

Insights

Metformin, an anti-cancer drug, inhibits centrosome amplification in aging Drosophila stem cells by down-regulating AKT/target of rapamycin (TOR) signaling. This suggests a new therapeutic strategy for age-related diseases and cancer prevention.

Area of Science:

  • Stem cell biology
  • Aging research
  • Cancer biology

Background:

  • Age-related stem cell dysfunction contributes to aging and diseases like cancer.
  • Centrosome amplification is a key feature of cancer.
  • Drosophila intestinal stem cells (ISCs) serve as a model for studying age-related centrosome amplification.

Purpose of the Study:

  • To elucidate the mechanism by which metformin inhibits centrosome amplification in Drosophila ISCs.
  • To investigate the role of AKT/TOR signaling in metformin's effect.
  • To explore the link between DNA damage and centrosome amplification.

Main Methods:

  • Utilized Drosophila intestinal stem cells (ISCs) as a model system.
  • Administered metformin to assess its effects on centrosome amplification.
  • Analyzed the AKT/TOR signaling pathway activity.
  • Investigated the correlation between DNA damage and centrosome amplification.

Main Results:

  • Metformin effectively inhibits age- and oxidative stress-induced centrosome amplification in ISCs.
  • This inhibition is mediated by the down-regulation of AKT/target of rapamycin (TOR) signaling.
  • A strong correlation was observed between DNA damage accumulation and centrosome amplification, suggesting a mediating role for DNA damage.

Conclusions:

  • Metformin exerts protective effects against centrosome amplification by modulating AKT/TOR signaling.
  • This study identifies a novel target for inhibiting age- and oxidative stress-induced centrosome amplification.
  • Drosophila ISCs are a valuable model for in vivo evaluation of anti-cancer drugs targeting stem cell aging.

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