Figure 3.
SIRT1 regulation of age-related physiology. SIRT1 activity can be regulated through NAD+ (nicotinamide adenine dinucleotide) and nicotinamide (NAM) concentrations, by SIRT1 protein level, and by phosphorylation; SIRT1 can be activated by active regulator of SIRT1 (AROS) and inhibited by DBC1 (deleted in breast cancer 1). SIRT1 activation promotes survival of neurons and protects cardiomyocytes from death. In the liver, SIRT1 promotes fatty acid oxidation and gluconeogenesis during nutrient deprivation via LXR, PGC-1α, and PPARα. In white adipose tissue (WAT), SIRT1 decreases fat storage by repressing PPARγ. SIRT1 promotes insulin secretion and pancreatic beta cell survival by suppressing UCP2 and interacting with FOXO, respectively. In skeletal muscle, SIRT1 promotes mitochondrial biogenesis through the activation of PGC-1α. Abbreviations: CNS, central nervous system; FOXO, forkhead box transcription factor, subgroup O; LXR, liver X receptor; NF-κB, nuclear factor kappa B; PGC-1α, peroxisome proliferator-activated receptor gamma coactivator 1 alpha; PPARα, peroxisome proliferators-activated receptor alpha; UCP2, uncoupling protein 2. Adapted from Reference 15.