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 inold age. SRT1720 is a specific SIRT1 activator that has health and lifespan benefits in adult mice fed ahigh-fat diet. We found extension in lifespan, delayedonset 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 invitro 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.