Figure 7. The Sirt1-LKB1-AMPK cascade in normal (A) vs. senescent cells (B). In senescent cells, a continuous decrease in ATP/ADP ratio leads to activation of AMPK. This leads to mitochondrial dysfunction induced by Sirt1-LKB1 down-regulation through a decreased PGC1α. Low ATP/ADP ratio decreases NAD+ production and induces Sirt1 inhibition. Continuous activation of AMPK leads to aging phenotypes such as cellular or tissue atrophy and fibrosis.