Sirtuins are NAD+-dependent proteinsimplicated in defense against aging, diabetes, stress and Alzheimer's Disease.Although sirtuins are regulated by the NAD+/NADH ratio,overexpression of Ndi1 in Drosophila did not increase Sir2 activity although flylifespan was extended by 20–40%, an effect attributed to diminishedmitochondrial ROS production [42]. The gene discussed is AVPR2; the disease is early-onset autosomal dominant Alzheimer disease.