Research Perspective Volume 3, Issue 4 pp 430—437

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.