Studies in a mouse model of Huntington’s disease show that reducing IRS2 level in brain induces lifespan extension of animals with improved mitochondrial function, autophagy, and oxidative stress resistance (Sadagurski et al., 2011), which is linked to increased nuclear localization of the transcription factor FOXO1 and expression of FOXO1-dependent genes that exert these beneficial effects. Here, FOXO1 is linked to Huntington disease.