Zebrafish as a Model Organism to Evaluate Drugs Potentially Able to Modulate Sirtuin Expression

Abstract

Sirtuins comprise a unique class of NAD(+)-dependent deacetylases that are key regulators of many physiological processes. They appear to be a potential target set of enzymes for treatment of age-associated diseases and have attracted interest in many research areas involving chemical and cellular investigations to understand them and discover potential ligands. For molecular screening, a cost-effective, easily manipulated, and consolidated model organism is needed, and the zebrafish fits these requirements perfectly. Here, we report the identification of sirtuin-related genes and their expression patterns in nine tissues of adult zebrafish. The investigation identified eight sirtuin-related genes, and their phylogenetic analysis resulted in seven well-resolved terminal clades, corresponding to each sirtuin (SIRT1, 2, 4-7) and two SIRT3 paralogs. Each gene showed a unique expression profile, illustrating a wide tissue distribution of sirtuins in zebrafish. SIRT1, SIRT3, SIRT5, and SIRT6 genes were expressed in all tissues, and SIRT1 exhibited the highest level of expression in all organs. A modulation experiment was performed using resveratrol, and results confirmed to the predicted scenario: altered sirtuin expression levels. Drugs based on sirtuin modulators may be tested using this system and could lead us to more selective and powerful therapies for age-related disorders.