Sirtuin1 (SIRT1) is an NAD+-dependent deacetylase involved in the regulation of calorie restriction pathways, which exert beneficial effects on insulin sensitivity and glucose homeostasis. SRT2104 is a synthetic activator of SIRT1. Treatment of C2C12 myoblasts with 3μM SRT2104 for 24 hours increased the protein expression of RelA/p65 compared to DMSO-treated controls. SRT2104 at the same dose also resulted in decreased acetylation of RelA/p65 in C2C12 myoblasts. The ability of SRT2104 to stimulate alkaline phosphatase activity in C2C12 cells was SIRT1 expression-dependent. The proliferation rate of C2C12 myoblasts was remarkably reduced by SRT2104 treatment (3μM). The supplementation of SRT2104 (100mg/kg) in standard AIN-93G diet significantly improved the survival of C57BL/6J mice with an increase in maximum lifespan of 4.9% and in mean lifespan of 9.7%. SRT2104-treated mice also showed better endurance performance on the treadmill and improved motor skills. The trabecular bone mineral density, trabecular connectivity, and trabecular bone volume were effectively improved in SRT2104-treated mice as compared to the control animals. SRT2104 supplementation also significantly decreased the serum levels of TNF-α (6.1 ± 0.7 vs. 3.9 ± 0.5pg/mL) and MCP-1 (72.0 ± 8.9 vs. 47.9 ± 8.9pg/mL) compared to the controls[3]. 100mg/kg of SRT2104 added to the diet significantly attenuated diabetes mellitus-induced aortic oxidative stress and inflammation, as 3-NT, 4-HNE, as well as the inflammatory markers VCAM-1 and ICAM-1 in the aortas of the diabetic mice were decreased by SRT2104[4].
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