Second, drugs that increase the concentration of NAD+, or mimic this effect, appear to activate the ATF5-UPRmt and SIRT3-UPRmt to extend lifespan and protect against NDD-related cellular and organismal decline in various model systems (Belenky et al., 2007; Houtkooper et al., 2013; Mouchiroud et al., 2013; Regitz et al., 2016; Lehmann et al., 2017; Sorrentino et al., 2017). The gene discussed is ATF5; the disease is Neurodevelopmental delay.