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. 2023 Jul 11;14:1207133. doi: 10.3389/fphys.2023.1207133

FIGURE 1.

FIGURE 1

Schematic of signaling molecules in various biological functions of Sirt6. Sirt6 activates poly-ADP-ribose polymerase 1 (PARP1) and promotes DNA damage repair. Sirt6 restores DNA damage through global genome nucleotide excision repair (NER). Sirt6 recruits SNF2H, a chromatin remodeler whose function is to safeguard against genomic instability. Sirt6 coordinates with chromodomain helicase DNA-binding protein 4 (CHD4) to repair DNA damage. Sirt6 activates AMPK signaling, upregulates Bcl-2 and inhibits NF-KB to alleviate ROS level. Sirt6 enhances Nrf2 abundance and exhibits antioxidant activity. Downregulation of FoxO6 upregulates Sirt6 and alleviates cardiomyocyte oxidative stress. Sirt6 represses NF-KB activity through various means and decreases production of the pro-inflammatory cytokine IL-1β. Sirt6 expedites the generation as well as releasing of inflammatory cytokine TNF-α.