SQSTM1 and neurodegenerative disease: [We note that while this paper was under revision, David Walker’s group reported that adult overexpression of Ref(2)/p62 in Drosophila similarly extends lifespan in an autophagy-dependent manner61.] While our data support previous observations showing that increasing p62 levels in neurodegenerative disease is beneficial in mice10, accumulation of p62 in mammals can be cytotoxic in some tissues, and can have cancerous effects under specific circumstances15,62.