Deficiency of Atg6 impairs beneficial effect of metformin on intestinal stem cell aging in Drosophila

Biochem Biophys Res Commun. 2018 Mar 25;498(1):18-24. doi: 10.1016/j.bbrc.2018.02.191. Epub 2018 Feb 27.

Abstract

Age-related changes of adult stem cell are crucial for tissue aging and age-related diseases. Thus, clarifying mechanisms to prevent adult stem cell aging is indispensable for healthy aging. Metformin, a drug for type 2 diabetes, has been highlighted for its anti-aging and anti-cancer effect. In Drosophila intestinal stem cell (ISC), we previously reported the inhibitory effect of metformin on age-related phenotypes of ISC. Here, we showed that knockdown of Atg6, a crucial autophagy-related factor, in ISC induces age-related phenotypes of ISC such as hyperproliferation, centrosome amplification, and DNA damage accumulation. Then, we revealed that metformin inhibits ISC aging phenotypes in Atg6-dependent manner. Taken together, our study suggests that Atg6 is required for the inhibitory effect of metformin on ISC aging, providing an intervention mechanism of metformin on adult stem cell aging.

Keywords: Aging; Atg6; Centrosome amplification; Drosophila; Intestinal stem cell; Metformin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Beclin-1 / deficiency*
  • Beclin-1 / metabolism
  • Cellular Senescence / drug effects*
  • Drosophila Proteins / deficiency*
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / cytology*
  • Drosophila melanogaster / drug effects
  • Drosophila melanogaster / metabolism
  • Gene Knockdown Techniques
  • Intestines / cytology*
  • Metformin / pharmacology*
  • Paraquat / toxicity
  • Phenotype
  • Signal Transduction / drug effects
  • Stem Cells / cytology*
  • Stem Cells / drug effects
  • Stem Cells / metabolism*

Substances

  • Atg6 protein, Drosophila
  • Beclin-1
  • Drosophila Proteins
  • Metformin
  • Paraquat