Overall, our findings are in agreement with the role of CYB5R3 and NQO1 as efficient intracellular generators of NAD+ for utilization by sirtuins (Ross & Siegel, 2017; Shen et al., 2017), and are consistent with the notion that modulation of SIRT1 and NAD+ levels represents a promising approach for the treatment of age‐associated metabolic diseases (Herranz et al., 2010; Imai, 2010; Verdin, 2015). Here, CYB5R3 is linked to metabolic disease.