Research Perspective Volume 3, Issue 4 pp 430—437

The physiological roles of Sirt1 in skeletal muscle


Figure 2. Changes in Sirt1 expression and activity controls muscle adaptation in response to environmental stress. Nutrient availability and mechanical stretch promote Sirt 1 transcription by two different mechanisms involving FoxO3a or Egr1 recruitment to the Sirt1 promoter. Glucose restriction and exercise diminish the ATP/AMP ratio, activate AMPK which leads to an increase in NAD availability by inducing Nmpt expression. The consequent increase in Sirt1 content and/or activity modulates the transcriptional activity of FoxO4 and PGC-1. Whereas PGC-1 promotes oxidative metabolism and the conversion from glycolitic to oxidative fibers, FoxO4 triggers a response that prevents oxidative damage. Dashed arrows indicate hypothetical mechanisms.