The SIRT1 Activator SRT1720 Extends Lifespan and Improves Health of Mice Fed a Standard Diet

The prevention or delay of the onset of age-related diseases prolongs survival and improves quality of life while reducing the burden on the health care system. Activation of sirtuin 1 (SIRT1), an NAD+-dependent deacetylase, improves metabolism and confers protection against physiological and cognitive disturbances in old age. SRT1720 is a specific SIRT1 activator that has health and lifespan benefits in adult mice fed a high-fat diet. We found extension in lifespan, delayed onset of age-related metabolic diseases, and improved general health in mice fed a standard diet after SRT1720 supplementation. Inhibition of proinflammatory gene expression in both liver and muscle of SRT1720-treated animals was noted. SRT1720 lowered the phosphorylation of NF-κB pathway regulators in vitro only when SIRT1 was functionally present. Combined with our previous work, the current study further supports the beneficial effects of SRT1720 on health across the lifespan in mice. [Display omitted] •SRT1720 supplementation extends mean lifespan of mice fed a standard diet•SRT1720 improves healthspan of mice fed a standard diet•SRT1720 reduces the age-associated increase in risk factors for metabolic disease•SRT1720 supplementation confers antiinflammatory properties in target tissues In this study, de Cabo and colleagues describe the beneficial effects of the SIRT1 activator SRT1720 on health and longevity in mice fed a standard diet. SRT1720 mediated the inhibition of proinflammatory gene expression in liver, and muscle was accompanied by a reduction in serum inflammatory markers. SIRT1 was required for the effects of SRT1720 on NF-κB suppression. These results suggest that SRT1720 mediates its beneficial effects on health and lifespan through reduction in the chronic proinflammatory state that occurs with normal aging.