Research Paper Volume 12, Issue 19 pp 18942—18956
Activation of LKB1 rescues 3T3-L1 adipocytes from senescence induced by Sirt1 knock-down: a pivotal role of LKB1 in cellular aging
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.