The Effect of SIRT6 on Metabolism and Beta Oxidation.

Abstract

With breakthroughs in scientific research that have extended human lifespan, there has been an increase in age-related metabolic diseases, confronting us with great medical obstacles. To overcome these obstacles, the mechanisms by which healthy ageing occurs must be better understood. Research is being conducted on the sirtuin family, a group of NAD+-dependent deacetylases that have been shown to play an important role in the regulation of extended lifespan and healthy aging through deacetylation of histones, thereby modifying and silencing chromatin. One area of focus is on metabolic pathways that increase longevity and their relationship to SIRT6, a member of the sirtuin family found to regulate gene expression and healthy ageing. The current study looked at the relationship between SIRT6 and PPAR- α, a transcription factor that regulates beta oxidation. We show here that PPAR-α and WY 14,643, a PPAR-α activator, function to activate gene expression of downstream PPAR-α genes involved in beta oxidation, though likely through different mechanisms. Additionally, we show that SIRT6 inhibits PPAR-α-mediated gene expression and PPRE activity. These results and continued research hold promise in using SIRT6 as a drug target to prevent metabolic diseases and to promote healthy ageing.