FOXO3 and metabolic disease: Another possible explanation could be due to the ability of SIRT1 to regulate other anti-aging genes such as Klotho, p66Shc, and the Forkhead box proteins (FOXO1/FOXO3a), which in turn is closely related to development of obesity and other metabolic diseases and could also depend on the SNVs of the SIRT 1 gene present in the population (Martins, 2016; Martins, 2017).