Research Paper Volume 1, Issue 4 pp 412—424
Dual targeting of the antagonistic pathways mediated by Sirt1 and TXNIP as a putative approach to enhance the efficacy of anti-aging interventions
Figure 7. Regulation of TXNIP through the glycolitic pathway and its modulation by limited glucose availability (LGA), resveratrol and DHEA. Down regulation of glucose levels is known to increase the AMP/ATP ratio which in turn activates AMPK, leading to increased serine phosphorylation of ChREBP. Phosphorylated ChREBP is unable to translocate into the nucleus and form a functional complex with Mlx that is required for TXNIP expression. In addition, reduced glucose levels would inhibit, the pentose pathway and lead to the inhibition of the phosphatase PP2A. This will also result in the accumulation of phosphorylated ChREBP in the cytoplasm and further inhibition of TXNIP expression. DHEA acts on this glycolytic pathway mainly through the inhibition of G6PD activity. Resveratrol would act through the induction of Sirt1-mediated phosphorylation of AMPK, leading to enhanced phosphorylation ChREBP and inhibition of its nuclear translocation. This mechanism sheds light on TXNIP as a common downstream target for putative anti-aging interventions that affect metabolism.