Anti-Aging Effect of the Ketone Metabolite ß-Hydroxybutyrate in Drosophila Intestinal Stem Cells.

ABSTRACT

Age-related changes in tissue-resident adult stem cells may be closely linked to tissue aging and age-related diseases, such as cancer. ß-Hydroxybutyrate is emerging as an important molecule for exhibiting the anti-aging effects of caloric restriction and fasting, which are generally considered to be beneficial for stem cell maintenance and tissue regeneration. The effects of ß-hydroxybutyrate on adult stem cells remain largely unknown. Therefore, this study was undertaken to investigate whether ß-hydroxybutyrate supplementation exerts beneficial effects on age-related changes in intestinal stem cells that were derived from the Drosophila midgut. Our results indicate that ß-hydroxybutyrate inhibits age- and oxidative stress-induced changes in midgut intestinal stem cells, including centrosome amplification (a hallmark of cancers), hyperproliferation, and DNA damage accumulation. Additionally, ß-hydroxybutyrate inhibits age- and oxidative stress-induced heterochromatin instability in enterocytes, an intestinal stem cells niche cells. Our results suggest that ß-hydroxybutyrate exerts both intrinsic as well as extrinsic influence in order to maintain stem cell homeostasis.