Remarkably, FOXO3 target reprogramming represses the transcription modulator and p16INK4a activator ETS2 (Irelan et al., 2009), which antagonizes p16INK4a expression and which may represent an adaptive response as p16INK4a promotes the senescence of human HD NSCs and MSNs. The gene discussed is FOXO3; the disease is Huntington disease.