Priority Research Paper Volume 1, Issue 6 pp 515—528
Inhibition of mammalian S6 kinase by resveratrol suppresses autophagy
- 1 Department of Pathology and Paul F.Glenn Laboratories for the Biological Mechanisms of Aging, Harvard Medical School, Boston, MA 02115, USA
- 2 Department of Medicine, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
- 3 These authors contributed equally tothis work
received: April 22, 2009 ; accepted: June 2, 2009 ; published: June 3, 2009 ;https://doi.org/10.18632/aging.100056
How to Cite
Resveratrol isa plant-derived polyphenol that promotes health and disease resistance inrodent models, and extends lifespan in lower organisms. A major challengeis to understand the biological processes and molecular pathways by whichresveratrol induces these beneficial effects. Autophagy is a criticalprocess by which cells turn over damaged components and maintain bioenergeticrequirements. Disruption of the normal balance between pro- andanti-autophagic signals is linked to cancer, liver disease, andneurodegenerative disorders. Here we show that resveratrol attenuatesautophagy in response to nutrient limitation or rapamycin in multiple celllines through a pathway independent of a known target, SIRT1. In alarge-scalein vitro kinase screen we identified p70 S6 kinase(S6K1) as a target of resveratrol. Blocking S6K1 activity by expression ofa dominant-negative mutant or RNA interference is sufficient to disruptautophagy to a similar extent as resveratrol. Furthermore,co-administration of resveratrol with S6K1 knockdown does not produce anadditive effect. These data indicate that S6K1 is important for the fullinduction of autophagy in mammals and raise the possibility that some ofthe beneficial effects of resveratrol are due to modulation of S6K1activity.