FOXO3 binds forkhead box elements in the promoter region of the SOD2 gene, encoding mitochondrial manganese-dependent superoxide dismutase (Kops et al. 2002). FOXO3-mediated upregulation of the SOD2 gene transcription is positively regulated by SIRT3 histone deacetylase, which deacetylates FOXO3 under conditions of oxidative stress and increases nuclear localization of FOXO3 (Sundaresan et al. 2009, Rangarajan et al. 2015, Yang et al. 2016).